@article{bddfd7e93bd345e99e05327e45e30c0c,
title = "Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn{\textquoteright}s disease",
abstract = "Background: The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown. Aim: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells. Methods: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer. Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient. Results: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. Conclusions: Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures.",
author = "Gregor Novak and Toer Stevens and {Van Viegen}, Tanja and Peter Bossuyt and Borut {\v S}tabuc and Jenny Jeyarajah and Guangyong Zou and Gaemers, {Ingrid C.} and McKee, {Trevor D.} and Fred Fu and Shackelton, {Lisa M.} and Reena Khanna and {van den Brink}, {Gijs R.} and Sandborn, {William J.} and Feagan, {Brian G.} and Pai, {Rish K.} and Vipul Jairath and {Vande Casteele}, Niels and Geert D{\textquoteright}Haens",
note = "Funding Information: Declaration of personal interests: GN reports consulting or speaker's fees from Takeda, Abbvie, MSD, Janssen, Octal pharma, Amgen, Pfizer, Ferring, Falk Pharma; TVV, JJ and GZ are employees of Robarts Clinical Trials, Inc; PB reports financial support for re‐ search from AbbVie, Mundipharma, Pfizer, Janssen, lecture fees from AbbVie, Takeda and Janssen, and advisory board fees from Takeda, Hospira, Janssen, MSD, Mundipharma, Roche, Pfizer, Sandoz and Dr Falk Benelux; LMS reports consulting fees from Robarts Clinical Trials, Inc.; RK reports consulting fees from AbbVie, Encycle, Janssen, Pfizer, Takeda and Robarts Clinical Trials Inc., and speaker fees from AbbVie, Janssen, Shire and Takeda; GRvdB is an employee of Hoffmann LaRoche; WJS reports research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, Abbvie, Janssen, Takeda, Lilly, Celgene/Receptos; consulting fees from Abbvie, Allergan, Amgen, Boehringer Ingelheim, Celgene, Conatus, Cosmo, Escalier Biosciences, Ferring, Genentech, Gilead, Janssen, Lilly, Miraca Life Sciences, Nivalis Therapeutics, Novartis Nutrition Science Partners, Oppilan Pharma, Otsuka, Paul Hastings, Pfizer, Precision IBD, Progenity, Prometheus Laboratories, Ritter Pharmaceuticals, Robarts Clinical Trials Inc., Salix, Shire, Seres Therapeutics, Sigmoid Biotechnologies, Takeda, Tigenix, Tillotts Pharma, UCB Pharma and Vivelix; and stock options from Ritter Pharmaceuticals, Oppilan Pharma, Escalier Biosciences, Precision IBD and Progenity; BGF reports grant/research support from AbbVie Inc., Amgen Inc., AstraZeneca/MedImmune Ltd., Atlantic Pharmaceuticals Ltd., Boehringer‐Ingelheim, Celgene Corporation, Celltech, Genentech Inc/Hoffmann‐La Roche Ltd., Gilead Sciences Inc., GlaxoSmithKline (GSK), Janssen Research & Development LLC., Pfizer Inc., Receptos Inc./Celgene International, Sanofi, Santarus Inc., Takeda Development Center Americas Inc., Tillotts Pharma AG and UCB, consulting fees from Abbott/AbbVie, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport Inc., Aptevo Therapeutics, Astra Zeneca, Atlantic Pharma, Avir Pharma, Biogen Idec, BioMx Israel, Boehringer‐Ingelheim, Bristol‐Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Gossamer Pharma, GSK, Inception IBD Inc, JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestle, Nextbiotix, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Funding Information: Receptos, Salix Pharma, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, Vivelix Pharma, VHsquared Ltd. and Zyngenia, speakers bureau fees from Abbott/ AbbVie, JnJ/Janssen, Lilly, Takeda, Tillotts and UCB Pharma, sci‐ entific advisory board membership for Abbott/AbbVie, Allergan, Amgen, Astra Zeneca, Atlantic Pharma, Avaxia Biologics Inc., Boehringer‐Ingelheim, Bristol‐Myers Squibb, Celgene, Centocor Inc., Elan/Biogen, Galapagos, Genentech/Roche, JnJ/Janssen, Merck, Nestle, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma AG and UCB Pharma, and is the Senior Scientific Officer of Robarts Clinical Trials Inc.; RKP reports fees from Janssen, AbbVie, Shire, Pfizer and Takeda Canada and from Robarts Clinical Trials, Inc.; VJ reports consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena pharmaceuticals, Genentech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, Celltrion, and speaker's fees from Takeda, Janssen, Shire, Ferring, Abbvie, Pfizer; NVC reports research support from R‐Biopharm and Takeda and consulting fees from Boehringer Ingelheim, Janssen, Pfizer, Progenity, Prometheus and Takeda, outside of the submitted work; GD'H reports consulting fees from Robarts Clinical Trials, per‐ sonal fees from Ablynx, Amakem, Amgen, AM Pharma, Boehringer‐ Ingelheim, Bristol Myers Squibb, Cosmo, Celgene, Celtrion, Covidien, Engene, Galapagos, Medimetrics, Mundipharma, Mitsubishi, Novonordisk, Pfizer, Receptos, Salix, Sandoz, Setpoint, Shire, Teva, Tigenix, Topivert, Versant and Vifor, grants and personal fees from Abbvie, Ferring, Glaxo Smith Kline, Jansen Biologics, Hospira, Merck Sharp Dome, Prometheus Labs, Robarts Clinical Trials, Takeda and Tillotts, and grants from Dr Falk Pharma and Photopill; TS, BS, ICG, TDM, FF have nothing to disclose. Publisher Copyright: {\textcopyright} 2019 John Wiley & Sons Ltd",
year = "2019",
month = jun,
doi = "10.1111/apt.15250",
language = "English (US)",
volume = "49",
pages = "1401--1409",
journal = "Alimentary Pharmacology and Therapeutics",
issn = "0269-2813",
publisher = "Wiley-Blackwell",
number = "11",
}