Review Article5-ASA and colorectal cancer chemoprevention in inflammatory bowel disease: Can we afford to wait for ‘best evidence’?
Section snippets
Is there a role for chemoprevention of colorectal cancer in patients with inflammatory bowel disease?
Patients with inflammatory bowel disease (IBD) carry a higher risk of developing colorectal cancer (CRC) as compared to the general population [1], [2]. Clinical factors that increase the risk include disease >10 years, extensive disease, a positive family history of sporadic CRC and the concomitant presence of primary sclerosing cholangitis (PSC) [2], [3]. Some studies also identified younger age at disease onset and, in patients with UC, the presence of backwash ileitis as additional risk
Mechanism(s) of action of 5-ASA in IBD-related CRC: lessons learned from aspirin
The mechanism(s) by which aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) act in the chemoprevention of CRC in non-IBD patients have not been completely elucidated. However, data concerning the chemopreventive effect of aspirin and NSAIDs and CRC are sound and are supported by a series of independent lines of evidence. Indeed, several epidemiological studies have shown an inverse correlation between aspirin intake and the risk of CRC [20], [21], [27]. Furthermore, studies on secondary
Experimental evidence of a chemopreventive effect of 5-ASA in IBD: what we have learned from the bench
Enterocyte proliferation rate and apoptosis seem to be the main mechanisms regulating intestinal epithelial homeostasis [33], [34], [35], [36]. Progressive accumulation of specific alterations in these two regulatory activities is strictly intertwined with the colonic carcinogenesis process. As a matter of fact, apoptosis progressively decreases and proliferation increases in the sequential steps from normal mucosa to CRC [37]. Inhibition of COX activity is one of the main mechanisms by which
The clinical evidence: does the existing data constitute sufficient evidence?
In 1994, Pinczowski et al. [64] carried out a retrospective, population-based, case-control study in a Swedish cohort of more than 3000 UC patients. The aim of the study was to evaluate the possible association between CRC and various factors, including therapy with sulphasalazine (SASP). They found that treatment with SASP was independently associated with a reduction in the relative risk of developing CRC (relative risk, 0.38; 95% CI, 0.20–0.69). Moreover, this effect was not influenced by
The negative studies
Not all clinical studies reported favourable results regarding the chemopreventive effect of 5-ASA on the development of CRC in IBD patients. Negative results mainly came from studies that reported positive results with other drugs such as folate or ursodiol [74], [75], [76]. The peculiarities of the cohorts enrolled in these studies may, at least in part, account for these inconsistencies. In fact, UC patients who were studied by Lashner et al. [74] were referred for several reasons including,
5-ASA and chemoprevention in IBD: can we ask for more from the available evidence?
Evidence-based medicine (EBM) is a tool that provides the clinician with a means to make medical decisions in clinical practice using published information, versus the recommendations made by ‘experts’. These recommendations may be subject to variability due to personal beliefs and knowledge [80], [81].
The basis for the formulation of EBM comes from the compilation of personal experience as well as from other colleagues’ experience, results of experimental studies, data from observational
Conclusions
Pharmacological treatment with the 5-ASAs is a well established mainstay of IBD therapy. In clinical practice, the application of EBM is of fundamental importance in order to improve and rationalise disease management. However, data regarding SASP or 5-ASA in IBD patients may not be rigorous enough to suggest their use as CRC chemopreventive drugs according to the highest level of EBM recommendations [81]. The argument to wait until we have Grade A evidence is not necessarily rational in this
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Synthesis, biological evaluation of chrysin derivatives as potential immunosuppressive agents
2011, European Journal of Medicinal ChemistryCitation Excerpt :It is reported that some salicylic acid derivatives showed potent anti-inflammatory activity [22–24]. For example, 5-aminosalicylic acid (5-ASA) was an active ingredient of agents used for the long term maintenance therapy to prevent relapses of inflammatory bowel diseases [25]. Besides, the methyl and some other esters of salicylic acids and their derivatives were found to have much lower gastric ulcerogenic activity compared with their corresponding acids [26–28].
Controversies in Ulcerative Colitis: A Survey Comparing Decision Making of Experts Versus Community Gastroenterologists
2009, Clinical Gastroenterology and HepatologyCitation Excerpt :Once remission is induced with mesalamine therapies, it remains unclear whether indefinite therapy is warranted to maintain remission, especially among those already on maintenance immunomodulators.19,20 Similarly, it is uncertain whether long-term mesalamine has important benefits for cancer chemoprevention.19,21,22 We asked the following question: “In a patient with UC in remission on 6MP/AZA, do you continue 5-ASA products?”
Nitric oxide as a target of complementary and alternative medicines to prevent and treat inflammation and cancer
2008, Cancer LettersCitation Excerpt :These include non-steroidal anti-inflammatory drugs, such as acetylsalicylic acid. A derivative, 5-acetylsalicylic acid (5-ASA), has been used with remarkable success in ameliorating mild to moderate bouts of inflammatory bowel disease [14]. The mechanisms of 5-ASA are not fully understood, but it inhibits COX-1 and COX-2 weakly, activates apoptosis, inhibits proliferation and NF-κB, scavenges RONS, and inhibits RON-associated base damage.
Inflammation, cancer, and targets of ginseng
2007, Journal of NutritionChemoprevention: Risk Reduction with Medical Therapy of Inflammatory Bowel Disease
2006, Gastroenterology Clinics of North AmericaCitation Excerpt :Because 5-ASAs are currently a safe and widely used therapy for IBD (especially UC), significant ethical concerns exist about withholding these medications from trial participants receiving placebo [66,70]. Additionally, because CRC-complicating colitis is still a relatively rare event with a long latency period, such a trial would require decades to enroll an adequate number of patients to detect a significant protective effect [66,70,71]. Given that an RCT is unlikely to be performed, systematic review and meta-analysis provide the best interpretation of the available data.
Colorectal cancer screening and surveillance
2006, Surgical Oncology Clinics of North AmericaCitation Excerpt :The risk of cancer may be reduced up to 40%–75% by the regular use of sulfasalazine or mesalamine [98,100,101]. This preventive measure should receive as much emphasis as surveillance [101]. In Inflammatory Bowel Disease (IBD), dysplasia may precede the development of CRC.