Natalizumab for active Crohn's disease.

BACKGROUND: In chronic inflammatory conditions such as Crohn's disease, the migration of leukocytes from the circulation into the parenchyma and their activation within inflammatory sites are mediated in part by alpha4 integrins. METHODS: We conducted a double-blind, placebo-controlled trial of the alpha4 integrin-specific humanized monoclonal antibody natalizumab in 248 patients with moderate-to-severe Crohn's disease. Patients were randomly assigned to receive one of four treatments: two infusions of placebo; one infusion of 3 mg of natalizumab per kilogram of body weight, followed by placebo; two infusions of 3 mg of natalizumab per kilogram; or two infusions of 6 mg of natalizumab per kilogram. Infusions were given four weeks apart. Outcomes included changes in scores for the Crohn's Disease Activity Index (higher scores indicate more severe disease), the health-related quality of life, and C-reactive protein levels. RESULTS: The group given two infusions of 6 mg of natalizumab per kilogram did not have a significantly higher rate of clinical remission (defined by a score of less than 150 on the Crohn's Disease Activity Index) than the placebo group at week 6 (the prospectively defined primary end point in the efficacy analysis). However, both groups that received two infusions of natalizumab had higher remission rates than the placebo group at multiple time points. Natalizumab also produced a significant improvement in response rates (defined by a reduction of at least 70 points in the score on the Crohn's Disease Activity Index). The highest remission rate was 44 percent and the highest response rate was 71 percent (at week 6 in the group given two infusions of 3 mg per kilogram). Overall, the two infusions of 6 mg of natalizumab per kilogram and of 3 mg per kilogram had similar effects. The quality of life improved in all natalizumab groups; C-reactive protein levels improved in groups receiving two infusions of natalizumab. The rates of adverse events were similar in all four groups. CONCLUSIONS: Treatment with the selective adhesion-molecule inhibitor natalizumab increased the rates of clinical remission and response, improved the quality of life and C-reactive protein levels, and was well tolerated in patients with active Crohn's disease.

Surgical treatment of gastric and small bowel gastrointestinal stromal tumours.

AIM: This study aimed to evaluate a set of gastrointestinal stromal tumours (GIST) of the stomach and the small bowel managed with a laparoscopic technique. MATERIAL AND METHODS: The study covers a period from January 1, 2007 until June 1, 2010 during which 13 patients underwent the laparoscopic removal of stomach tumours and 2 patients underwent the removal of a small bowel GIST in the General Hospital in Pardubice. In all cases tumours were removed in a laparoscopic way, including the healthy border of the stomach tissue. RESULTS: No death was observed in our study. Two patients suffered from wound infection (secondary healing), one of them requiring repeat surgery owing to the excessive narrowing of the distal part of the stomach. Dehiscence of laparoscopic sutures or other intra-abdominal complications were not observed. During monitoring all patients were free of signs of local recurrence, but tumour progression into the liver was observed in 1 patient. Gastrointestinal stromal tumours are very rare tumours but their incidence is increasing. At this time the consensus about the necessity of preoperative unambiguous differentiation between malignant or less malignant variants is not available. Strict differentiation is very difficult and the decision whether to choose a more radical surgical approach for more malignant variants is not clear-cut. CONCLUSIONS: In cases of gastric and small bowel GISTs the local removal of a tumour with the healthy border of the stomach tissue may be chosen as an adequate approach. Our results support this local surgical approach.