title: Relationship between proximal Crohn's disease location and disease behavior and surgery: a cross-sectional study of the IBD Genetics Consortium.
abstract: OBJECTIVE
  In classifying Crohn's disease (CD) location, proximal (L4) disease includes esophagogastroduodenal (EGD) and jejunal disease. Our aim was to determine the influence of proximal disease on outcomes of behavior and need for surgery and to determine if there was significant clinical heterogeneity between EGD and jejunal disease.
  
  
  METHODS
  We performed a cross-sectional query of the NIDDK (National Institute of Diabetes and Digestive and Kidney Disease) Inflammatory Bowel Disease Genetics Consortium (IBDGC) database of patients with a confirmed diagnosis of CD and phenotyped per the IBDGC manual. Presence of any L4, L4-EGD, L4-jejunal, and non-L4 disease (L1-ileal, L2-colonic, and L3-ileocolonic) was compared with demographic features including age, race, ethnicity, smoking and inflammatory bowel disease (IBD) family history, diagnosis age, disease duration, clinical outcomes of inflammatory, stricturing or penetrating behavior, and CD abdominal surgeries. Univariate and multivariable analyses were performed with R.
  
  
  RESULTS
  Among 2,105 patients with complete disease location data, 346 had L4 disease (175 L4-EGD, 115 L4-jejunal, and 56 EGD and jejunal) with 321 having concurrent L1-L3 disease. In all, 1,759 had only L1-L3 disease. L4 vs. non-L4 patients were more likely (P<0.001) to be younger at diagnosis, non-smokers, have coexisting ileal involvement, and have stricturing disease. L4-jejunal vs. L4-EGD patients were at least twice as likely (P<0.001) to have had ileal disease, stricturing behavior, and any or multiple abdominal surgeries. Remarkably, L4-jejunal patients had more (P<0.001) stricturing behavior and multiple abdominal surgeries than non-L4 ileal disease patients. Logistic regression showed stricturing risks were ileal (without proximal) site (odds ratio (OR) 3.18; 95% confidence interval 2.23-4.64), longer disease duration (OR 1.33/decade; 1.19-1.49), jejunal site (OR 2.90; 1.89-4.45), and older age at diagnosis (OR 1.21/decade; 1.10-1.34). Multiple surgery risks were disease duration (OR 3.74/decade; 3.05-4.64), penetrating disease (OR 2.60; 1.64-4.21), and jejunal site (OR 2.39; 1.36-4.20), with short duration from diagnosis to first surgery protective (OR 0.87/decade to first surgery; 0.84-0.90).
  
  
  CONCLUSIONS
  Jejunal disease is a significantly greater risk factor for stricturing disease and multiple abdominal surgeries than either EGD or ileal (without proximal) disease. The Montreal site classification should be revised to include separate designations for jejunal and EGD disease.
authors.affiliation: Division of Gastroenterology, Meyerhoff Inflammatory Bowel Diseases Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. mlazare1@jhmi.edu
authors.forename: Mark
authors.initials: M
authors.lastname: Lazarev
authors.forename: Chengrui
authors.initials: C
authors.lastname: Huang
authors.forename: Alain
authors.initials: A
authors.lastname: Bitton
authors.forename: Judy H
authors.initials: JH
authors.lastname: Cho
authors.forename: Richard H
authors.initials: RH
authors.lastname: Duerr
authors.forename: Dermot P
authors.initials: DP
authors.lastname: McGovern
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Proctor
authors.forename: Miguel
authors.initials: M
authors.lastname: Regueiro
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
authors.forename: Philip P
authors.initials: PP
authors.lastname: Schumm
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
authors.forename: A Hillary
authors.initials: AH
authors.lastname: Steinhart
authors.forename: Susan
authors.initials: S
authors.lastname: Hutfless
authors.forename: Steven R
authors.initials: SR
authors.lastname: Brant
mesh_terms: D000328:Adult; D003251:Constriction, Pathologic / Q000209:etiology / Q000601:surgery; D003424:Crohn Disease / Q000145:classification / Q000150:complications / Q000473:pathology* / Q000601:surgery; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D004386:Duodenum / Q000473:pathology*; D004947:Esophagus / Q000473:pathology*; D005260:Female; D006801:Humans; D007079:Ileitis / Q000150:complications / Q000473:pathology / Q000601:surgery; D007415:Intestinal Obstruction / Q000209:etiology / Q000601:surgery; D007583:Jejunum / Q000473:pathology*; D008297:Male; D015999:Multivariate Analysis; D010641:Phenotype; D012307:Risk Factors