title: Anastomotic configuration and mucosal 5-aminosalicyclic acid (5-ASA) concentrations in patients with Crohn's disease: a GISC study. Gruppo Italiano per lo Studio del Colon e del Retto.
abstract: OBJECTIVE
  Recurrence of Crohn's disease quite inevitably occurs after resection of distal small bowel and proximal colon, involving the neoterminal ileum close to the anastomosis. Oral 5-aminosalicylic acid (5-ASA) administered soon after surgery delays recurrence and reduces its severity. We recently observed that in operated patients submitted to prophylactic treatment with oral 5-ASA the rate of recurrence was significantly higher in those with end-to-end anastomosis than in those with other types of anastomosis (end-to-side, side-to-side). The hypothesis investigated in the present study was that patients with end-to-side or side-to-side anastomosis would benefit from a higher mucosal concentration of 5-ASA with respect to patients with end-to-end anastomosis. Therefore, the mucosal 5-ASA concentration was measured in the perianastomotic area of both groups.
  
  
  METHODS
  The study was carried out in 19 patients submitted to radical surgery for Crohn's ileitis or ileocolitis, under oral prophylactic treatment with 5-ASA (Asacol). All patients were on regular endoscopic follow-up and were free of recurrence. Two biopsies were collected 3 cm from the anastomosis, in the neoterminal ileum, and two biopsies were collected at the colonic site 3 cm below the anastomosis. 5-ASA concentrations (ng/mg) were measured in tissue homogenates by high-performance liquid chromatography (HPLC) with electrochemical detection.
  
  
  RESULTS
  The mucosal concentration of 5-ASA in the neoterminal ileum was significantly lower in patients with end-to-end anastomosis than in those with other types of anastomosis (median values: 29.4 ng/mg vs 92.9 ng/mg respectively; p < 0.001). Six of 10 patients (60%) with end-to-end anastomosis, but none of the nine patients with other types of anastomosis, showed 5-ASA mucosal concentrations <40 ng/mg at the neoterminal ileum. On the contrary, no patients with end-to-end anastomosis showed mucosal concentrations of 5-ASA >90 ng/mg, compared with the 57% of patients in the group with other types of anastomosis. No differences were observed for colonic biopsies.
  
  
  CONCLUSIONS
  The different mucosal concentrations in these two groups may be explained by the difference in segmental transit time induced by the different anastomotic configurations. A slower preanastomotic transit time, demonstrated in patients with end-to-side or side-to-side anastomosis, could offer a prolonged contact time between the intestinal content and the mucosa, resulting in an increase in drug absorption.
authors.affiliation: Cattedra di Gastroenterologia, Università dell'Aquila, L'Aquila, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Frieri
authors.forename: M T
authors.initials: MT
authors.lastname: Pimpo
authors.forename: G
authors.initials: G
authors.lastname: Palumbo
authors.forename: F
authors.initials: F
authors.lastname: Tonelli
authors.forename: V
authors.initials: V
authors.lastname: Annese
authors.forename: G C
authors.initials: GC
authors.lastname: Sturniolo
authors.forename: A
authors.initials: A
authors.lastname: Andreoli
authors.forename: M
authors.initials: M
authors.lastname: Comberlato
authors.forename: G
authors.initials: G
authors.lastname: Corrao
authors.forename: R
authors.initials: R
authors.lastname: Caprilli
mesh_terms: D000328:Adult; D000714:Anastomosis, Surgical / Q000379:methods; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007079:Ileitis / Q000188:drug therapy / Q000378:metabolism; D007082:Ileum / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D019804:Mesalamine / Q000378:metabolism* / Q000627:therapeutic use; D008875:Middle Aged; D009994:Osmolar Concentration; D014018:Tissue Distribution
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine