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      Assessment of preoperative exercise capacity in hepatocellular carcinoma patients with chronic liver injury undergoing hepatectomy

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          Abstract

          Background

          Cardiopulmonary exercise testing measures oxygen uptake at increasing levels of work and predicts cardiopulmonary performance under conditions of stress, such as after abdominal surgery. Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. This study examined the relationship between preoperative exercise capacity and event-free survival in hepatocellular carcinoma (HCC) patients with chronic liver injury who underwent hepatectomy.

          Methods

          Sixty-one HCC patients underwent preoperative cardiopulmonary exercise testing to determine their anaerobic threshold (AT). The AT was defined as the break point between carbon dioxide production and oxygen consumption per unit of time (VO 2). Postoperative events including recurrence of HCC, death, liver failure, and complications of cirrhosis were recorded. Univariate and multivariate analyses were performed to evaluate associations between 35 clinical factors and outcomes, and identify independent prognostic indicators of event-free survival and maintenance of Child-Pugh class.

          Results

          Multivariate analyses identified preoperative branched-chain amino acid/tyrosine ratio (BTR) <5, alanine aminotransferase level ≥42 IU/l, and AT VO 2 <11.5 ml/min/kg as independent prognostic indicators of event-free survival. AT VO 2 <11.5 ml/min/kg and BTR <5 were identified as independent prognostic indicators of maintenance of Child-Pugh class.

          Conclusions

          This study identified preoperative exercise capacity as an independent prognostic indicator of event-free survival and maintenance of Child-Pugh class in HCC patients with chronic liver injury undergoing hepatectomy.

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          Most cited references28

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          Epidemiology of primary liver cancer.

          Liver cancer (LC) ranks fifth in frequency in the world with an estimated number of 437,000 new cases in 1990. In developing countries, incidence rates are two- to three-fold higher than in developed countries. The geographic areas at highest risk are located in Eastern Asia, with age-adjusted incidence rates (AAIRs) ranking from 27.6 to 36.6 per 100,000 in men; Middle Africa, with AAIRs ranking from 20.8 to 38.1 per 100,000 in men; and some countries of Western Africa, with AAIRs ranking from 30 to 48 per 100,000 in men. The geographic areas at lowest LC risk are Northern Europe, Australia, New Zealand, and the Caucasian populations in North and Latin America, with AAIRs below 5.0 per 100,000 in men. Excess of LC incidence among men compared to women is universal, with sex ratios between 1.5 and 3.0. Significant variations in LC incidence among different ethnic groups living in the same geographical area and among migrants of the same ethnic groups living in different areas have been extensively described. The variability of LC incidence rates between countries and within countries, strongly suggests differences in exposure to risk factors. The role of chronic infection with the Hepatitis B and hepatitis C viruses (HBV and HCV) in the etiology of LC is well established. The attributable risk estimates for LC for each of these hepatotropic viruses vary among countries but the combined effects of persistent HBV or HCV infections account for well over 80% of LC cases worldwide. Other documented risk factors such as aflatoxin exposure in diets, cigarette smoking, alcohol consumption, and oral contraceptives may explain the residual variation between and within countries. Interactions between some risk factors have been postulated, and are subject of active research. New laboratory techniques and biological markers such as polymerase chain reaction detection of HBV DNA and HCV RNA, as well as specific mutations related to aflatoxin exposure may help to provide quantitative estimates of the risk related to each these factors.
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            Oxygen uptake kinetics for various intensities of constant-load work.

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              Lipid and lipoprotein dysregulation in insulin resistant states.

              Insulin resistant states are commonly associated with an atherogenic dyslipidemia that contributes to significantly higher risk of atherosclerosis and cardiovascular disease. Indeed, disorders of carbohydrate and lipid metabolism co-exist in the majority of subjects with the "metabolic syndrome" and form the basis for the definition and diagnosis of this complex syndrome. The most fundamental defect in these patients is resistance to cellular actions of insulin, particularly resistance to insulin-stimulated glucose uptake. Insulin insensitivity appears to cause hyperinsulinemia, enhanced hepatic gluconeogenesis and glucose output, reduced suppression of lipolysis in adipose tissue leading to a high free fatty acid flux, and increased hepatic very low density lipoprotein (VLDL) secretion causing hypertriglyceridemia and reduced plasma levels of high density lipoprotein (HDL) cholesterol. Although the link between insulin resistance and dysregulation of lipoprotein metabolism is well established, a significant gap of knowledge exists regarding the underlying cellular and molecular mechanisms. Emerging evidence suggests that insulin resistance and its associated metabolic dyslipidemia result from perturbations in key molecules of the insulin signaling pathway, including overexpression of key phosphatases, downregulation and/or activation of key protein kinase cascades, leading to a state of mixed hepatic insulin resistance and sensitivity. These signaling changes in turn cause an increased expression of sterol regulatory element binding protein (SREBP) 1c, induction of de novo lipogensis and higher activity of microsomal triglyceride transfer protein (MTP), which together with high exogenous free fatty acid (FFA) flux collectively stimulate the hepatic production of apolipoprotein B (apoB)-containing VLDL particles. VLDL overproduction underlies the high triglyceride/low HDL-cholesterol lipid profile commonly observed in insulin resistant subjects.
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                Author and article information

                Journal
                BMC Gastroenterol
                BMC Gastroenterol
                BMC Gastroenterology
                BioMed Central
                1471-230X
                2013
                22 July 2013
                : 13
                : 119
                Affiliations
                [1 ]Department of Surgery, Hirakata Hospital, Kansai Medical University, 573-191 Hirakata, Osaka, Japan
                [2 ]Department of Nutritional Medicine, Graduate School of Human Life Science, Osaka City University, 545-8585 Osaka, Japan
                [3 ]Department of Nutrition Management, Hirakata Hospital, Kansai Medical University, 573-191 Hirakata, Osaka, Japan
                [4 ]Health Science Center, Hirakata Hospital, Kansai Medical University, 573-191 Hirakata, Osaka, Japan
                [5 ]Masaki Kaibori, Department of Surgery, Hirakata Hospital, Kansai Medical University, 2-3-1 Shinmachi, 573-1191 Hirakata, Osaka, Japan
                Article
                1471-230X-13-119
                10.1186/1471-230X-13-119
                3725155
                23875788
                5447ad13-0871-4f53-bcac-a56dda519662
                Copyright ©2013 Kaibori et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 August 2012
                : 19 July 2013
                Categories
                Research Article

                Gastroenterology & Hepatology
                liver cancer,chronic liver injury,hepatectomy,exercise capacity,bcaa/tyrosine ratio

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