In favour of prophylactic treatment for post-operative recurrence in Crohn's disease

Abstract

Endoscopic follow-up of patients resected for ileal Crohn's disease have shown that, in the absence of treatment, the post-operative recurrence rate is 70-90% within one year of the operation and 83-100% within 3 years. Post-operative recurrence requires further operation in approximately half the patients in a 10-year period of follow-up. Therapeutic strategies aimed to prevent recurrence are, therefore, needed. Evidence supporting the administration of drugs early after surgery are listed below. Evidence from morphological and immunological studies: minimal mucosal lesions have been found using scanning electron microscopy in unaffected specimens of ileum and colon from 2/3 of patients resected for Crohn's disease. An increased production of TNF alpha, IL-1 beta, IL-6 and phospholipase A2 has also been found in the unaffected mucosa of patients with Crohn's disease providing evidence for a sustained immune stimulation in Crohn's disease even in the absence of patent inflammation. These inflammatory mediators are inhibited "in vitro" by aminosalicylates and, therefore, their use early after surgery is justified. Evidence from randomised controlled trials: several randomised controlled clinical trials have shown that aminosalicylates are able to prevent post-operative recurrence. In particular, an Italian study demonstrated that the cumulative proportion of endoscopic recurrence at 36 months was significantly lower in patients treated with Asacol compared to controls (0.57 +/- 0.12 vs 0.83 +/- 0.07, p = 0.003). A less frequent occurrence of severe complications and reoperations was also observed in the Asacol group. A North American study confirmed these results at 3 years' follow-up using Salofalk. Additional evidence for effectiveness of aminosalicylates in the prevention of post-operative recurrence was provided by two more studies in which Pentasa was used. Further evidence in favour of 5-ASA treatment comes from a recent metanalysis which showed that 5-ASA is effective as maintenance treatment in Crohn's disease, in particular in patients with resection. Metronidazole and fish-oil have also been found to be useful in the prevention of post-operative recurrence in isolated reports but need further investigation. Finally, cigarette smoking and end-to-end anastomosis are considered to be associated with an increased risk of recurrence. Overall, these data suggest that to stop smoking, avoiding end-to-end anastomosis and early administration of admino-salicylates after surgery should be recommended for all patients resected for Crohn's disease.