title: Measurement of fecal calprotectin improves monitoring and detection of recurrence of Crohn's disease after surgery.
abstract: OBJECTIVE
  Crohn's disease (CD) usually recurs after intestinal resection; postoperative endoscopic monitoring and tailored treatment can reduce the chance of recurrence. We investigated whether monitoring levels of fecal calprotectin (FC) can substitute for endoscopic analysis of the mucosa.
  
  
  METHODS
  We analyzed data collected from 135 participants in a prospective, randomized, controlled trial, performed at 17 hospitals in Australia and 1 hospital in New Zealand, that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of C-reactive protein (CRP), and Crohn's disease activity index (CDAI) scores were measured before surgery and then at 6, 12, and 18 months after resection of all macroscopic Crohn's disease. Ileocolonoscopies were performed at 6 months after surgery in 90 patients and at 18 months after surgery in all patients.
  
  
  RESULTS
  Levels of FC were measured in 319 samples from 135 patients. The median FC level decreased from 1347 μg/g before surgery to 166 μg/g at 6 months after surgery, but was higher in patients with disease recurrence (based on endoscopic analysis; Rutgeerts score, ≥i2) than in patients in remission (275 vs 72 μg/g, respectively; P < .001). Combined 6- and 18-month levels of FC correlated with the presence (r = 0.42; P < .001) and severity (r = 0.44; P < .001) of CD recurrence, but the CRP level and CDAI score did not. Levels of FC greater than 100 μg/g indicated endoscopic recurrence with 89% sensitivity and 58% specificity, and a negative predictive value (NPV) of 91%; this means that colonoscopy could have been avoided in 47% of patients. Six months after surgery, FC levels less than 51 μg/g in patients in endoscopic remission predicted maintenance of remission (NPV, 79%). In patients with endoscopic recurrence at 6 months who stepped-up treatment, FC levels decreased from 324 μg/g at 6 months to 180 μg/g at 12 months and 109 μg/g at 18 months.
  
  
  CONCLUSIONS
  In this analysis of data from a prospective clinical trial, FC measurement has sufficient sensitivity and NPV values to monitor for CD recurrence after intestinal resection. Its predictive value might be used to identify patients most likely to relapse. After treatment for recurrence, the FC level can be used to monitor response to treatment. It predicts which patients will have disease recurrence with greater accuracy than CRP level or CDAI score.
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Wright
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia. Electronic address: mkamm@unimelb.edu.au.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kamm
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: De Cruz
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Hamilton
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Ritchie
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.
authors.forename: Efrosinia O
authors.initials: EO
authors.lastname: Krejany
authors.affiliation: School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Leach
authors.affiliation: Melbourne EpiCentre, University of Melbourne, Melbourne, Australia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gorelik
authors.affiliation: Melbourne EpiCentre, University of Melbourne, Melbourne, Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Liew
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
authors.forename: Lani
authors.initials: L
authors.lastname: Prideaux
authors.affiliation: Centre for Inflammatory Bowel Diseases, Fremantle Hospital, Freemantle, Australia; The University of Western Australia, Fremantle, Australia.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Lawrance
authors.affiliation: Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia; University of Adelaide, Adelaide, Australia.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Andrews
authors.affiliation: Department of Gastroenterology and Hepatology, Flinders Medical Centre, Adelaide, Australia; Flinders University, Adelaide, Australia.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Bampton
authors.affiliation: Department of Gastroenterology, Alfred Health, Melbourne, Australia; Monash University, Melbourne, Australia.
authors.forename: Simon L
authors.initials: SL
authors.lastname: Jakobovits
authors.affiliation: Department of Gastroenterology, Mater Health Services, Brisbane, Australia.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Florin
authors.affiliation: Department of Gastroenterology, Alfred Health, Melbourne, Australia; Monash University, Melbourne, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Gibson
authors.affiliation: Melbourne Gastrointestinal Investigation Unit, Cabrini Hospital, Melbourne, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Debinski
authors.affiliation: University of Melbourne, Melbourne, Australia; Department of Colorectal Medicine and Genetics, and Department of Medicine, Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Finlay A
authors.initials: FA
authors.lastname: Macrae
authors.affiliation: Department of Gastroenterology, Bankstown Hospital, Sydney, Australia.
authors.forename: Douglas
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Department of Gastroenterology, Western Hospital, Melbourne, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Kronborg
authors.affiliation: IBD Group Queensland Institute of Medical Research, University of Queensland, Brisbane, Australia; Department of Gastroenterology, Royal Brisbane and Womens Hospital, Brisbane, Australia.
authors.forename: Graeme
authors.initials: G
authors.lastname: Radford-Smith
authors.affiliation: AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Warwick
authors.initials: W
authors.lastname: Selby
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Johnston
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.
authors.forename: Rodney
authors.initials: R
authors.lastname: Woods
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.
authors.forename: P Ross
authors.initials: PR
authors.lastname: Elliott
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Bell
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Brown
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia.
authors.forename: William R
authors.initials: WR
authors.lastname: Connell
authors.affiliation: Department of Paediatrics, University of Otago, Christchurch, New Zealand.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Day
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Desmond
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Gearry
mesh_terms: D000328:Adult; D001315:Australia; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D003113:Colonoscopy; D003424:Crohn Disease / Q000175:diagnosis / Q000378:metabolism / Q000601:surgery*; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D002097:C-Reactive Protein
keywords: Fecal Biomarkers; Inflammatory Bowel Disease; Prognosis; Prognostic Factor