Postsurgical recurrence of ileal Crohn's disease: an update on risk factors and intervention points to a central role for impaired host-microflora homeostasis.
BACKGROUND
A pressing need exists to identify factors that predispose to recurrence after terminal ileal resection for Crohn's disease (CD) and to determine effective prophylactic strategies. This review presents an up-to-date summary of the literature in the field and points to a role for bacterial overproliferation in recurrence.


METHODS
The literature (Medline, Embase, and the Cochrane Library, 1971-2009) on ileal CD and postoperative recurrence was searched, and 528 relevant articles were identified and reviewed.


RESULTS
Smoking is a key independent risk factor for recurrence. NOD2/CARD15 polymorphisms and penetrating phenotype are associated with aggressive disease and higher reoperation rates. Age at diagnosis, disease duration, gender, and family history are inconsistent predictors of recurrence. Prophylactic 5-aminosalicylic acid therapy and nitromidazole antibiotics are beneficial. Combination therapies with immunosuppressants are also effective. Anti-TNFalpha-based regimens show benefit but the evidence base is small. Corticosteroid, interleukin-10, and probiotic therapies are not effective. Wider, stapled anastomotic configurations are associated with reduced recurrence rates. Strictureplasty and laparoscopic approaches have similar long-term recurrence rates to open resection techniques. Length of resection and presence of microscopic disease at resection margins do not influence recurrence. A lack of consensus exists regarding whether the presence of granulomas or plexitis affects outcome.


CONCLUSIONS
Current evidence points to defects in mucosal immunity and intestinal dysbiosis of either innate (NOD2/CARD15) or induced (smoking) origin in postoperative CD recurrence. Prophylactic strategies should aim to limit dysbiosis (antibiotics, side-to-side anastomoses) or prevent downstream chronic inflammatory sequelae (anti-inflammatory, immunosuppressive, and immunomodulatory therapy).
Cunningham
Michael F
MF
Surgical Professorial Unit, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
Docherty
Neil G
NG
Coffey
J Calvin
JC
Burke
John P
JP
O'Connell
P Ronan
PR
D003424:Crohn Disease / Q000453:epidemiology* / Q000235:genetics / Q000382:microbiology / Q000473:pathology / Q000601:surgery; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006706:Homeostasis; D006801:Humans; D007079:Ileitis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000601:surgery; D007082:Ileum / Q000382:microbiology* / Q000473:pathology; D010535:Laparoscopy; D008019:Life Style; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D012307:Risk Factors; D055502:Secondary Prevention; D012907:Smoking / Q000453:epidemiology*
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein