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      About Digestion: 3.2 Impact Factor I 6.4 CiteScore I 0.914 Scimago Journal & Country Rank (SJR)

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      Vascular Endothelial Growth Factor Improves Liver Regeneration and Survival after 90% Hepatectomy in a Rat Model of Diet-Induced Steatosis

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          Abstract

          Background/Aims: Fatty liver disease increases the risk in major liver resection for patients. As previous studies suggested that vascular endothelial growth factor (VEGF) and erythropoietin (EPO) might improve liver regeneration in nonobese animals, we investigated their effect after subtotal hepatectomy (SH) in rats with diet-induced steatosis. Methods: Male Wistar rats were fed with fatty liver-inducing diet (FLD) or normal diet (control) for 11-12 weeks followed by 90% SH. Animals were treated either with EPO, VEGF or NaCl on postoperative days 0, 1 and 3 and sacrificed 24 h or 7 days after SH. Survival rate, liver regeneration and biochemical markers were assessed. Expression of inflammatory cytokines (TNF-α, IL-6) and apoptosis-related genes (PUMA, Bcl-2) was measured by qRT-PCR. Results: Seven-day survival after SH was significantly decreased in the FLD group compared to controls (50 vs. 100%, p < 0.05). In FLD animals, treatment with VEGF increased 7-day survival to 90% compared to only 40% in the EPO group. After surgery, blood glucose levels of VEGF but not EPO- or NaCl-treated animals remained normal. Inflammatory genes were markedly upregulated in the EPO group 24 h after SH. Conclusions: Steatosis severely impairs survival and regeneration after extensive liver resection, which can be counteracted at least in part by perioperative treatment with VEGF.

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          Most cited references33

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          Is Open Access

          Adipose Tissue Overexpression of Vascular Endothelial Growth Factor Protects Against Diet-Induced Obesity and Insulin Resistance

          During the expansion of fat mass in obesity, vascularization of adipose tissue is insufficient to maintain tissue normoxia. Local hypoxia develops and may result in altered adipokine expression, proinflammatory macrophage recruitment, and insulin resistance. We investigated whether an increase in adipose tissue angiogenesis could protect against obesity-induced hypoxia and, consequently, insulin resistance. Transgenic mice overexpressing vascular endothelial growth factor (VEGF) in brown adipose tissue (BAT) and white adipose tissue (WAT) were generated. Vessel formation, metabolism, and inflammation were studied in VEGF transgenic mice and wild-type littermates fed chow or a high-fat diet. Overexpression of VEGF resulted in increased blood vessel number and size in both WAT and BAT and protection against high-fat diet–induced hypoxia and obesity, with no differences in food intake. This was associated with increased thermogenesis and energy expenditure. Moreover, whole-body insulin sensitivity and glucose tolerance were improved. Transgenic mice presented increased macrophage infiltration, with a higher number of M2 anti-inflammatory and fewer M1 proinflammatory macrophages than wild-type littermates, thus maintaining an anti-inflammatory milieu that could avoid insulin resistance. These studies suggest that overexpression of VEGF in adipose tissue is a potential therapeutic strategy for the prevention of obesity and insulin resistance.
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            Trends in perioperative outcome after hepatic resection: analysis of 1500 consecutive unselected cases over 20 years.

            To estimate risk factors affecting the early outcome after hepatic resection in a high volume center specialized in hepatobiliary surgery and to analyze the changing of results during 3 different periods of treatment. Retrospective review. A series of 1500 consecutive patients who underwent hepatic resection. Postoperative morbidity and mortality were analyzed in relation to indications for surgery, period of operation, patient characteristics, and intraoperative variables. Patients were classified into 4 groups, according to the indication for surgery: primary liver tumors with cirrhosis (group 1, G1); other liver malignancies (group 2, G2); biliary malignancies (group 3, G3); and benign diseases (group 4, G4). Patients were also divided into 3 groups, according to the year of operation (period 1: June 1985 to October 1993; period 2: November 1993 to September 1999; period 3: October 1999 to September 2007). Overall mortality and morbidity were 3% and 22.5%, respectively. Multivariate analysis revealed that blood transfusions, G1, and additional procedures were associated with an increased risk of postoperative complications, whereas blood transfusions, G1, G3, and extended hepatectomy were associated with an increased risk of postoperative mortality. G1 decreased, whereas G3, extended hepatectomies and additional procedures significantly increased between periods 2 and 3 (P < 0.05). The complication rate was significantly lower in period 2 (18.8%) compared with period 1 (23.8%) and period 3 (24.8%). Similarly, there was a significantly lower mortality rate in period 2 (1.6%) compared with period 1 (3.4%) and period 3 (4%). Slightly worse short-term outcomes in liver surgery were observed in recent years, with a concomitant increase of the aggressiveness of operative strategies. Nevertheless, the present results still justify an aggressive approach in liver resections.
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              The epidemiology, pathogenesis and histopathology of fatty liver disease.

              Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD. © 2012 Blackwell Publishing Ltd.
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                Author and article information

                Journal
                DIG
                Digestion
                10.1159/issn.0012-2823
                Digestion
                S. Karger AG
                0012-2823
                1421-9867
                2013
                December 2013
                22 November 2013
                : 88
                : 4
                : 235-242
                Affiliations
                Departments of aGeneral, Visceral and Transplantation Surgery, and bGastroenterology and Hepatology, University Hospital, University of Duisburg-Essen, Essen, Germany
                Author notes
                *Prof. Joerg F. Schlaak, MD, Department of Gastroenterology and Hepatology, University Hospital of Essen, Hufelandstr. 55, DE-45122 Essen (Germany), E-Mail joerg.schlaak@uni-due.de
                Article
                355528 Digestion 2013;88:235-242
                10.1159/000355528
                24281241
                197c3bca-3ffa-46e6-a2e6-384bc4f52c6c
                © 2013 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 13 December 2012
                : 09 September 2013
                Page count
                Figures: 6, Pages: 8
                Categories
                Original Paper

                Oncology & Radiotherapy,Gastroenterology & Hepatology,Surgery,Nutrition & Dietetics,Internal medicine
                Gene expression,Liver regeneration ,Vascular endothelial growth factor,Fatty liver disease,Liver resection,Erythropoietin

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