Metabolic surgery and cancer

Department of Surgery and Cancer, Imperial College London, London, England.
Cancer (Impact Factor: 4.89). 05/2011; 117(9):1788-99. DOI: 10.1002/cncr.25738
Source: PubMed


The worldwide epidemic of obesity and the global incidence of cancer are both increasing. There is now epidemiological evidence to support a correlation between obesity, weight gain, and some cancers. Metabolic or bariatric surgery can provide sustained weight loss and reduced obesity-related mortality. These procedures can also improve the metabolic profile to decrease cardiovascular risk and resolve diabetes in morbidly obese patients. The operations offer several physiological steps, the so-called BRAVE effects: 1) bile flow alteration, 2) reduction of gastric size, 3) anatomical gut rearrangement and altered flow of nutrients, 4) vagal manipulation and 5) enteric gut hormone modulation. Metabolic operations are also associated with a significant reduction of cancer incidence and mortality. The cancer-protective role of metabolic surgery is strongest for female obesity-related tumors; however, the underlying mechanisms may involve both weight-dependent and weight-independent effects. These include the improvement of insulin resistance with attenuation of the metabolic syndrome as well as decreased oxidative stress and inflammation in addition to the beneficial modulation of sex steroids, gut hormones, cellular energetics, immune system, and adipokines. Elucidating the precise metabolic mechanisms of cancer prevention by metabolic surgery can increase our understanding of how obesity, diabetes, and metabolic syndrome are associated with cancer. It may also offer novel treatment strategies in the management of tumor generation and growth.

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Available from: Kamran Ahmed, Oct 08, 2014
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    • "There is emerging evidence that weight loss using bariatric surgery may reduce the incidence of cancer [112]. It seems that the protective effect is strongest for women, and the reduction of risk may be as high as 60% [6,112,113]. The mechanisms underlying this apparent risk reduction are unclear, but may involve mediation of inflammatory pathways and attenuation of obesity associated hyperinsulinism [112]. "
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    ABSTRACT: Obesity is recognized as a global health crisis. Bariatric surgery offers a treatment that can reduce weight, induce remission of obesity-related diseases, and improve the quality of life. In this article, we outline the different options in bariatric surgery and summarize the recommendations for selecting and assessing potential candidates before proceeding to surgery. We present current data on post-surgical outcomes and evaluate the psychosocial and economic effects of bariatric surgery. Finally, we evaluate the complication rates and present recommendations for post-operative care.
    Full-text · Article · Jan 2013 · BMC Medicine
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    • "Nonetheless, new evidence suggests that an increased hip circumference is associated with premenopausal breast cancer [2]. Multiple reports document that weight loss after gastric bypass surgery leads to a reduced risk of cancer, with the strongest effect on female obesity related tumors [17]. This risk reduction is thought to involve alterations in adipokines, sex steroid hormones and other proteins [17], but the specific proteins that influence risk and risk reduction after weight loss are for the most part unknown. "
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    ABSTRACT: Obesity has long been associated with postmenopausal breast cancer risk and more recently with premenopausal breast cancer risk. We previously observed that nipple aspirate fluid (n) levels of prostate specific antigen (PSA) were associated with obesity. Serum (s) levels of adiponectin are lower in women with higher body mass index (BMI) and with breast cancer. We conducted a prospective study of obese women who underwent gastric bypass surgery to determine: 1) change in n- and s-adiponectin and nPSA after surgery and 2) if biomarker change is related to change in BMI. Samples (30-s, 28-n) and BMI were obtained from women 0, 3, 6 and 12 months after surgery. There was a significant increase after surgery in pre- but not postmenopausal women at all time points in s-adiponectin and at 3 and 6 months in n-adiponectin. Low n-PSA and high s-adiponectin values were highly correlated with decrease in BMI from baseline. Adiponectin increases locally in the breast and systemically in premenopausal women after gastric bypass. s-adiponectin in pre- and nPSA in postmenopausal women correlated with greater weight loss. This study provides preliminary evidence for biologic markers to predict weight loss after gastric bypass surgery.
    Full-text · Article · Jan 2012 · BMC Research Notes
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    • "In contrast to reports from large-scale human epidemiological cohorts suggesting a reduced cancer risk following bariatric surgery (Ashrafian et al., 2011a), we have demonstrated increased fecal cytotoxicity in this Wistar rat model following RYGB surgery; which can be associated with increased colonic cancer risk (de Kok and van Maanen, 2000). Two possible explanations for the conflicting RYGB effects between humans and rats include: (i) the rat model is not translational to humans with regard to RYGB surgery, or more controversially that the RYGB surgery increases the cytotoxicity of feces, however human colonocytes, are subject to a high degree of oxidative stress and possess enzymes capable of detoxifying H 2 S and other toxins (Ramasamy et al., 2006), are resistant to this toxicity. "
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    ABSTRACT: Bariatric surgery, also known as metabolic surgery, is an effective treatment for morbid obesity, which also offers pronounced metabolic effects including the resolution of type 2 diabetes and a decrease in cardiovascular disease and long-term cancer risk. However, the mechanisms of surgical weight loss and the long-term consequences of bariatric surgery remain unclear. Bariatric surgery has been demonstrated to alter the composition of both the microbiome and the metabolic phenotype. We observed a marked shift toward Gammaproteobacteria, particularly Enterobacter hormaechei, following Roux-en-Y gastric bypass (RYGB) surgery in a rat model compared with sham-operated controls. Fecal water from RYGB surgery rats was highly cytotoxic to rodent cells (mouse lymphoma cell line). In contrast, fecal water from sham-operated animals showed no/very low cytotoxicity. This shift in the gross structure of the microbiome correlated with greatly increased cytotoxicity. Urinary phenylacetylglycine and indoxyl sulfate and fecal gamma-aminobutyric acid, putrescine, tyramine, and uracil were found to be inversely correlated with cell survival rate. This profound co-dependent response of mammalian and microbial metabolism to RYGB surgery and the impact on the cytotoxicity of the gut luminal environment suggests that RYGB exerts local and global metabolic effects which may have an influence on long-term cancer risk and cytotoxic load.
    Full-text · Article · Sep 2011 · Frontiers in Microbiology
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