Intraoperative Hyperglycemia during Liver Resection: Predictors and Association with the Extent of Hepatocytes Injury

<div><p>Background</p><p>Patients undergoing liver resection are at risk for intraoperative hyperglycemia and acute hyperglycemia is known to induce hepatocytes injury. Thus, we aimed to evaluate whether intraoperative hyperglycemia during liver resection is associated with the extent of hepatic injury.</p><p>Methods</p><p>This 1 year retrospective observation consecutively enrolled 85 patients undergoing liver resection for hepatocellular carcinoma. Blood glucose concentrations were measured at predetermined time points including every start/end of intermittent hepatic inflow occlusion (IHIO) <i>via</i> arterial blood analysis. Postoperative transaminase concentrations were used as surrogate parameters indicating the extent of surgery-related acute hepatocytes injury.</p><p>Results</p><p>Thirty (35.5%) patients developed hyperglycemia (blood glucose > 180 mg/dl) during surgery. Prolonged (≥ 3 rounds) IHIO (odds ratio [OR] 7.34, <i>P</i> = 0.004) was determined as a risk factors for hyperglycemia as well as cirrhosis (OR 4.07, <i>P</i> = 0.022), lower prothrombin time (OR 0.01, <i>P</i> = 0.025), and greater total cholesterol level (OR 1.04, <i>P</i> = 0.003). Hyperglycemia was independently associated with perioperative increase in transaminase concentrations (aspartate transaminase, β 105.1, standard error 41.7, <i>P</i> = 0.014; alanine transaminase, β 81.6, standard error 38.1, <i>P</i> = 0.035). Of note, blood glucose > 160 or 140 mg/dl was not associated with postoperative transaminase concentrations.</p><p>Conclusions</p><p>Hyperglycemia during liver resection might be associated with the extent of hepatocytes injury. It would be rational to maintain blood glucose concentration < 180 mg/dl throughout the surgery in consideration of parenchymal disease, coagulation status, lipid profile, and the cumulative hepatic ischemia in patients undergoing liver resection for hepatocellular carcinoma.</p></div

Significant difference in perioperative increase of AST (‘x’ mark) and ALT (‘o’ mark) according to the occurrence of intraoperative hyperglycemia (HG).

<p>Significant difference in perioperative increase of AST (‘x’ mark) and ALT (‘o’ mark) according to the occurrence of intraoperative hyperglycemia (HG).</p

Up-and-down blood glucose fluctuation in response to clamping (C) and unclamping (U) of intermittent hepatic inflow occlusion (IHIO). I, anesthetic induction.

<p>Up-and-down blood glucose fluctuation in response to clamping (C) and unclamping (U) of intermittent hepatic inflow occlusion (IHIO). I, anesthetic induction.</p

Probability of intraoperative hyperglycemia in relation to the increase in prothrombin time internationalized ratio and serum total cholesterol concentration.

<p>Probability of intraoperative hyperglycemia in relation to the increase in prothrombin time internationalized ratio and serum total cholesterol concentration.</p

Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model-1

<p><b>Copyright information:</b></p><p>Taken from "Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model"</p><p>http://www.biomedcentral.com/1471-2407/7/87</p><p>BMC Cancer 2007;7():87-87.</p><p>Published online 23 May 2007</p><p>PMCID:PMC1903361.</p><p></p>f CT26 tumor-bearing mice treated with plasmids were harvested at 7 days after plasmid injection, and cells analyzed by flow cytometry using the corresponding FITC- or PE- or PE-Cy5-labeled antibodies and isotype control

Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model-5

<p><b>Copyright information:</b></p><p>Taken from "Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model"</p><p>http://www.biomedcentral.com/1471-2407/7/87</p><p>BMC Cancer 2007;7():87-87.</p><p>Published online 23 May 2007</p><p>PMCID:PMC1903361.</p><p></p>oses of control plasmid or that expressing IL-18 until day 7 after tumor inoculation. Liver tissue was obtained on day 4 after direct injection of IL-18 plasmid DNA, and ELISA used to evaluate IL-18 protein levels. Representative data determined from two separate experiments

Multivariate analysis for intraoperative hyperglycemia during liver resection.

<p>Due to concern of multicollinearity prothrombin time and total cholesterol level were separately enrolled into the multivariate model. Odds ratio and P values of other variables were described based on the model with prothrombin time internationalized ratio (INR).</p><p>Multivariate analysis for intraoperative hyperglycemia during liver resection.</p

Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model-4

<p><b>Copyright information:</b></p><p>Taken from "Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model"</p><p>http://www.biomedcentral.com/1471-2407/7/87</p><p>BMC Cancer 2007;7():87-87.</p><p>Published online 23 May 2007</p><p>PMCID:PMC1903361.</p><p></p>, and cultured with anti-CD3 and anti-CD28 antibodies for 3 days before performing ELISA (* = 0.006)

Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model-3

<p><b>Copyright information:</b></p><p>Taken from "Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model"</p><p>http://www.biomedcentral.com/1471-2407/7/87</p><p>BMC Cancer 2007;7():87-87.</p><p>Published online 23 May 2007</p><p>PMCID:PMC1903361.</p><p></p>edium alone or that containing CT26 lysates. Numbers within the gates in the FACS plots depict the percentage of CD69IFN-γCD4cells. Data are presented from experiments that were repeated at least twice

Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model-2

<p><b>Copyright information:</b></p><p>Taken from "Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model"</p><p>http://www.biomedcentral.com/1471-2407/7/87</p><p>BMC Cancer 2007;7():87-87.</p><p>Published online 23 May 2007</p><p>PMCID:PMC1903361.</p><p></p>smid DNA was injected directly into the tumors on day 7. Tumor growth was measured on days 1, 4, 7, and 14 after plasmid implantation. Data are presented as the mean of tumor weights of 8 mice/group