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The rising problem of obesity is causing major health problems, reduced quality of life and reduced life expectancy. It now generates approximately 10% of all health costs. The progression of the problem indicates preventive measures have been unsuccessful so far. Only bariatric surgical treatments have been able to achieve substantial and durable weight loss. Gastric banding and gastric bypass are used in more than 90% of bariatric operations. The proportion of each varies from greater than 95% bands in Australia, about 50/50 in Europe and USA and nearly 100% bypass in South America. The availability of follow up is a prime determinant of choice. Understanding the mechanisms of effect for the bariatric procedures is central to optimizing their effect. The traditional narrow concepts of restrictive (blocking the transit of food) and malabsorptive (preventing the absorption of food) should be discarded and the importance of induction of satiety, change of taste, diversion of chyme, neural and hormonal mediation and the effects of aversion need to be included. The primary mechanism of effect for gastric banding is the generation of a background of satiety and early post-prandial satiation via specifically structured vagal afferents at the level of the band. At five years after banding or bypass, there is typically a loss of 30-35 kg representing 50-60% of excess weight. This weight loss has been shown to be associated with major improvement or complete resolution of multiple common and serious health problems plus improvement in quality of life and in survival. Level 1 evidence supports the use of the gastric band over optimal lifestyle therapy. Randomized controlled trials has shown gastric banding to achieve better weight loss, health and quality of life than optimal lifestyle therapies for adults above a BMI of 30 and adolescents above a BMI of 35. In adults with mild to severe obesity and type 2 diabetes gastric banding leads to remission in three out of four individuals. Perioperative risk is significant with gastric bypass and late revisional procedures can be required after both procedures. Gastric banding is indicated in any adult who has a BMI over 30, has problems with their obesity and has made substantial effort to reduce their weight by lifestyle methods. Gastric bypass or biliopancreatic diversion should be considered in those with BMI greater than 35 if banding is contraindicated or has been unsuccessful. [ABSTRACT FROM AUTHOR]

Abstract Background Standard non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal cancer; however, their use as preventive agents is limited by their inherent toxicity. Drugs that selectively inhibit cyclooxygenase-2 (COX-2) may be useful in this setting as they are supposedly less toxic. No study has directly compared the ability of standard NSAIDs and selective COX-2 inhibitors to inhibit colorectal cancer at clinically relevant doses. Methods Aberrant crypt foci (ACF) were induced in Sprague–Dawley rats by using 1,2-dimethylhydrazine (DMH). Test agents or vehicle were then administered for 3 weeks, twice daily through orogastric gavage. At the end of this period, the number and multiplicity of ACF were determined. The agents tested at equivalent anti-inflammatory doses were: sulindac and indomethacin (standard NSAIDs), meloxicam (selective COX-2 inhibitor), celecoxib (specific COX-2 inhibitor) and sulindac sulfone (no known COX activity). Acute gastrotoxicity of NSAID in rats was compared by using quantitative histology. Results All test agents reduced the number of ACF. There was a 42% reduction with indomethacin, 46% with sulindac, 46% with meloxicam, 22% with celecoxib and 36% with sulindac sulfone. Only the COX-2 inhibitors caused no significant gastrotoxicity in rats. Conclusions Cyclooxygenase-2 inhibitors are potentially ideal chemopreventive agents as they inhibit ACF and are not gastrotoxic. [ABSTRACT FROM AUTHOR]

Abstract Background Standard non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal cancer; however, their use as preventive agents is limited by their inherent toxicity. Drugs that selectively inhibit cyclooxygenase-2 (COX-2) may be useful in this setting as they are supposedly less toxic. No study has directly compared the ability of standard NSAIDs and selective COX-2 inhibitors to inhibit colorectal cancer at clinically relevant doses. Methods Aberrant crypt foci (ACF) were induced in Sprague–Dawley rats by using 1,2-dimethylhydrazine (DMH). Test agents or vehicle were then administered for 3 weeks, twice daily through orogastric gavage. At the end of this period, the number and multiplicity of ACF were determined. The agents tested at equivalent anti-inflammatory doses were: sulindac and indomethacin (standard NSAIDs), meloxicam (selective COX-2 inhibitor), celecoxib (specific COX-2 inhibitor) and sulindac sulfone (no known COX activity). Acute gastrotoxicity of NSAID in rats was compared by using quantitative histology. Results All test agents reduced the number of ACF. There was a 42% reduction with indomethacin, 46% with sulindac, 46% with meloxicam, 22% with celecoxib and 36% with sulindac sulfone. Only the COX-2 inhibitors caused no significant gastrotoxicity in rats. Conclusions Cyclooxygenase-2 inhibitors are potentially ideal chemopreventive agents as they inhibit ACF and are not gastrotoxic. [ABSTRACT FROM AUTHOR]