BACKGROUND: Cancer cells are highly dependent on glycolysis. Our aim was to determine if switching metabolism from glycolysis towards mitochondrial respiration would reduce growth preferentially in colorectal cancer cells over normal cells, and to examine the underlying mechanisms. METHODS: Representative colorectal cancer and non-cancerous cell lines were treated with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase. RESULTS: Dichloroacetate (20 mM) did not reduce growth of non-cancerous cells but caused significant decrease in cancer cell proliferation (P ¼ 0.009), which was associated with apoptosis and G 2 phase cell-cycle arrest. The largest apoptotic effect was evident in metastatic LoVo cells, in which DCA induced up to a ten-fold increase in apoptotic cell counts after 48 h. The most striking G 2 arrest was evident in well-differentiated HT29 cells, in which DCA caused an eight-fold increase in cells in G 2 phase after 48 h. Dichloroacetate reduced lactate levels in growth media and induced dephosphorylation of E1a subunit of pyruvate dehydrogenase complex in all cell lines, but the intrinsic mitochondrial membrane potential was reduced in only cancer cells (P ¼ 0.04). CONCLUSIONS: Pyruvate dehydrogenase kinase inhibition attenuates glycolysis and facilitates mitochondrial oxidative phosphorylation, leading to reduced growth of colorectal cancer cells but not of non-cancerous cells.

A large number of patients undergoing bariatric surgery are deficient in copper, and Roux-en-Y gastric bypass can further aggravate it. Delays in diagnosis and treatment of copper deficiency can leave patients with residual neurological disability. This has led to recommendation from the British Obesity and Metabolic Surgery Society that copper levels should be monitored annually after gastric bypass. This review concludes that copper deficiency in adequately supplemented patients is rare and can be adequately treated if a related haematological or neurological disorder is diagnosed. The cost of routine monitoring may therefore not be justified for adequately supplemented, asymptomatic patients who have undergone Roux-en-Y gastric bypass. The screening may however be necessary for high-risk patient groups to prevent severe complications and permanent disability.

More than 80 years ago, Otto Warburg described the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions, a process subsequently referred to as the Warburg effect or aerobic glycolysis. The exact molecular mechanisms underlying cancers reliance on glycolysis remains unclear, but is likely a combination of an epigenetic response to the hypoxic tumour environment in combination with direct oncogenic stimulation. The aim of the current manuscript is to review the normal process of glycolysis and highlight the alterations that occur with malignant transformation, to consider the potential advantages of glycolytic respiration for cancer cell survival, and finally to explore areas where altered glucose metabolism can be exploited for clinical benefit.

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Management of super-super obese patients poses a particular challenge for bariatric surgeons. Many staged algorithms exist for these patients. Essentially all of these involve a lower-risk procedure like sleeve gastrectomy first before a definitive second-stage procedure like gastric bypass or duodenal switch. This study compares our results with 19 mini (one anastomosis) gastric bypass and 56 sleeve gastrectomy in super-super obese patients. Sleeve gastrectomy patients were significantly older. There was no mortality or major complication in either group. There was no minor complication in mini (one anastomosis) gastric bypass group compared to two in the sleeve gastrectomy group. Mini (one anastomsosis) gastric bypass patients experienced significantly higher weight loss compared to sleeve gastrectomy patients at 6 months, 1 year, and 2 years after surgery.

Surgeons not performing OAGB/MGB cite a number of concerns for not performing this operation. This survey is the first scientific attempt to understand these objections scientifically.

Mortality from locally advanced and metastatic cancer remains high despite advances in our understanding of the molecular basis of the disease and improved adjuvant therapies. Recently, there has been an increased interest in cancer metabolomics, and in particular, the potential for targeting glucose metabolism, for therapeutic gain. This interest stems from the fact that cancer cells metabolize glucose very differently from normal cells. Cancer cells preferentially switch to aerobic glycolysis rather than oxidative phosphorylation as their means of glucose metabolism. This metabolic switch is believed to enhance cancer cell survival. Several therapeutic agents that target tumor metabolism have shown significant cancer cell cytotoxicity in preclinical studies, and some have progressed to clinical trials. In this review, we discuss the alteration of carbohydrate metabolism seen in cancer cells, the underlying mechanisms, and opportunities for targeting cancer metabolism for therapeutic purposes.

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