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5-Aminosalicylic acid therapy and the risk of colorectal cancer among patients with inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) affecting the colon are at increased risk of developing colorectal cancer (CRC). Published data are conflicting about whether 5-aminosalicylic acid (5-ASA) has chemopreventive properties against IBD-related carcinogenesis. The objective of this observational study was to determine if an association between 5-ASA therapy and CRC risk exists in IBD patients. METHODS: Adult patients with a new CRC diagnosis (n = 18,440) were identified from 2 large administrative claims databases. For each case, 20 control patients with no record of CRC diagnosis or bowel surgery (n = 368,800) were identified. RESULTS: An IBD diagnosis was associated with a 6- to 7-fold increased risk of CRC (ulcerative colitis, crude odds ratio [OR] = 6.72, 95% CI, 5.79-7.81; Crohn's disease, crude OR = 6.60, 95% CI, 5.56-7.82). Among patients with IBD (364 CRC cases, 1172 controls), exposure to 5-ASA therapy of any dose or duration during the 12 months before CRC diagnosis was not associated with a reduced risk of CRC (OR = 0.97; 95% CI, 0.77-1.23). However, there was a trend toward a decreased risk of CRC with increasing number of mesalamine prescriptions in the previous year, though statistical significance was not achieved (trend P = 0.08). CONCLUSIONS: Treating IBD patients with 5-ASA medications was not found to have a protective effect against colitis-related CRC when assessed over a short period of exposure.

Aged↗

Scintigraphic imaging and absorption of a 5-aminosalicylic acid enema in patients with ileorectal anastomosis.

UNLABELLED: Ileorectal anastomosis (IRA) is a possible surgical treatment for hyperacute and drug-unresponsive forms of ulcerative colitis (UC). UC relapses in the rectal remnant usually are prevented by chronic administration of 5-aminosalicylic acid (5-ASA) in topical formulations. The relationships between intestinal absorption and pattern of luminal spread of 5-ASA enemas are still unknown in patients with IRA. We correlated the absorption of a 5-ASA enema with its spread in the distal bowel of patients with IRA as assessed by 99mTc radioenema imaging. METHODS: Eight patients with UC in remission and previous IRA received a therapeutic 50-mL 5-ASA enema labeled with 99mTc-sulfer colloid. Absorbed 5-ASA and its major metabolite, acetyl 5-ASA, were measured in plasma, and dynamic images of radiolabeled enema were obtained for 6 h. The retrograde ileal spread (RIS) was determined and expressed as percentage of total enema radioactivity. Plasma levels of 5-ASA and acetyl 5-ASA were measured in six healthy volunteers after administration of the same enema volume with no radiolabeling. RESULTS: The mean 5-ASA plasma level was 0.70 microg/mL (range 0.37-0.95 microg/mL) in patients and 0.96 microg/mL (range 0.78-1.16 microg/mL) in healthy volunteers (P = not significant), and the mean acetyl 5-ASA plasma levels were 0.89 microg/mL (range 0.44-1.19 microg/mL) and 0.84 microg/mL (range 0.51-1.02 microg/mL), respectively (P = not significant). Radioenema imaging allows RIS assessment of patients with IRA. The mean value was 8.5% (range 2%-19.3%) of administered radioactivity, which correlated significantly with the total absorption of 5-ASA in the IRA group (P = 0.033, linear correlation test). Rectal wall contractions recognized by dynamic radioenema imaging were defined as a common cause of RIS episodes. CONCLUSION: In IRA patients, 5-ASA plasma levels were similar to those in healthy volunteers after administration in enema. Only part of a 50-mL 5-ASA enema reaches the ileum, and radiolabeled imaging shows the degree and number of these RIS episodes. The absorption of 5-ASA can increase in patients compared with healthy volunteers, in the presence of either occasional but significant ileal spread associated with postural factors and abdominal wall contraction or multiple moderate episodes of radioenema backdiffusion related to rectal wall motility.

Adult↗

5-aminosalicylic acid enhances anchorage-independent colorectal cancer cell death.

Resistance to anoikis, the cell death triggered by the loss of anchorage to the substratum, is an essential prerequisite in the proliferation and diffusion of colorectal cancer (CRC) cells. We examined whether 5-aminosalicylic acid (5-ASA), a drug that seems to reduce the risk of colitis-associated CRC, enhances CRC cell anoikis. To this end, Colo205 cells were treated with 5-ASA in the presence or absence of inhibitors of caspases (zVAD-fmk) and reactive oxygen species (ROS). We demonstrate that 5-ASA enhances Colo205 cell death. Although 5-ASA induces dissipation of mitochondrial transmembrane potential and caspase-3 activation, zVAD-fmk does not completely prevent the 5-ASA-induced cell death. 5-ASA also enhances the synthesis of ROS. However, inhibitors of ROS reduce the fraction of 5-ASA-induced Colo205 cell death but do not confer protection. In contrast, the 5-ASA-mediated Colo205 cell death is preventable by Bcl-2 over-expression. These data suggest a mechanism by which 5-ASA interferes with colon carcinogenesis.

Anoikis↗

[5-aminosalicylic acid and chronic inflammatory bowel diseases in children].

5-Aminosalicylate (mesalazine; 5-AS) represents a new therapeutic strategy in chronic inflammatory bowel disease. The drug (active metabolite of sulfasalazine) has proven its clinical efficacy and safety in numerous controlled studies in adults. However only limited data are available for the pediatric population. This brief review summarises the published spares information on this promising agent. As pharmacokinetic properties of 5-AS are age-independent and since 5-AS has a wide margin of safety clinical studies and use of this drug should be encouraged also in children.

Administration, Oral↗