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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Each vascular occlusion technique has a place in major and minor hepatic resectional surgery, based on the tumor location, presence of associated underlying liver disease, patient cardiovascular status, and experience of the operating surgeon. Understanding of the potential application of different techniques, anticipation of the expected and potential hemodynamic responses, and knowledge of the limitations of each technique are fundamental to appropriate surgical planning adapted to each patient. Experience with the various clamping methods enables an aggressive but safe approach to surgical treatment of hepatobiliary diseases, with acceptable blood loss and transfusion requirements. In all cases, surgical strategy should be defined with the anesthesiologist, particularly in regard to hemodynamic monitoring, in order to optimize perioperative patient management and to minimize the risk for complications such as bleeding and air embolism. Importantly, randomized study has shown that the added dissection, operative, and postoperative risks associated with HVE are not balanced by decreased blood loss compared with hepatic pedicle clamping, except in exceptional cases when tumors involve the major hepatic veins or vena cava. In addition, dissection in preparation for clamping may be used as safe approach techniques to tumors in difficult locations, even when eventual clamping is not performed. Similarly, the liver-hanging maneuver enables resection without mobilization, compression, and manipulation of large tumors. In the future, renewed interest in the impact of hepatic ischemia and reperfusion may reveal that some clamping methods, in particular inflow occlusion, act as a means of preconditioning before a period of prolonged hepatic ischemia, for complex hepatic resection or for graft harvest from a living donor. Finally, the addition of infrahepatic caval clamping may add a new, simple, effective technique to the armamentarium of the liver surgeon, particularly as more routine hepatic surgery moves from the specialized center to the community.
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PMID:Hepatic vascular occlusion: which technique? 1506 62

With the increasing success of liver transplantation (OLT), more patients above 70 years of age are being considered for OLT. There is not enough data about the predictors for survival in this patient population. We retrospectively analyzed the medical records of 33 patients at least 70 years of age who received 34 OLT from July 1995 to July 2002. There were 16 women and 17 men of mean age 73.7 years. Etiologies of end-stage liver disease (ESLD) were: HCV (17/33, 52%), cryptogenic cirrhosis (8/33, 24%), PBC (3/33, 9%), Laennec's cirrhosis (2/33, 6%), and others (3/33, 9%). According to the UNOS classification, 15/34 (44%) were status 3, 16/34 (47%) status 2, and 3/34 (9%) status 1. Among 13/33 patients who died (39%), 1-year and 3-year survival rates were 78.79% and 71.43%, respectively. Based on UNOS criteria, 4/15 (26%) were status 3; 6/16 (37%), status 2; and 3/3 (100%), status 1 (P value = .04 for status 1 patients). There was no statistical differences between the scores using the Model for End-Stage Liver Disease (MELD) among those who died (MELD (19) versus MELD (17.35) respectively (P = .50). There was a statistically significant difference in cold ischemia time (CIT) and warm ischemia time (WIT) between those who died (P = .024 and.010, respectively). These results suggest that in this group of patients UNOS status classification, CIT and WIT correlate with survival. The sample size was too small to derive a conclusion about the association with the MELD score.
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PMID:Liver transplant for the septuagenarians: importance of patient selection. 1525 55

Living donor liver transplantation has increasingly become an alternative to cadaveric donor liver transplants for select adult patients. Because these cases can be performed electively, living donor recipients may have better compensated liver disease at the time of surgery than cadaver donor recipients. However, it is unknown if this difference would have a significant effect on their intraoperative course. Therefore, we compared the intraoperative fluid management of patients receiving liver grafts from either living or cadaveric donors (n = 25, each group). Patient groups did not differ in demographics or baseline laboratory values. The duration of anesthesia and anhepatic phases were significantly longer in living donor cases (651 +/- 80 minutes vs 409 +/- 20 and 55 +/- 14 vs 45 +/- 6, P < .05). Adjusted for anesthesia time and patient weight, fluid administration (crystalloid and albumin) was not different between the two groups. Intraoperative transfusion requirements were also not significantly different in recipients from living donors versus cadaveric donors with regard to red blood cells, fresh frozen plasma, platelets, and cryoprecipitate. However, arterial oxygenation was better preserved in recipients from living donors. The PaO2/FiO2 (P/F) ratio at the end of the procedure was significantly better in patients receiving livers from living rather than from cadaveric donors (P/F ratio 335 +/- 114 mm Hg vs 271 +/- 174, P < .05). Our results indicate that while intraoperative fluid and transfusion requirements are similar, the impact of transplantation on pulmonary gas exchange is more pronounced in patients receiving organs from cadaveric donors. This difference may arise from longer cold ischemia times present in the cadaveric donor group.
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PMID:Intraoperative fluid management of living donor versus cadaveric liver transplant recipients. 1525 59

Live donor liver transplantation (LDLT) has become increasingly common in the United States and around the world. In this study, we compared the outcome of 764 patients who received LDLT in the United States and compared the results with a matched population that received deceased donor transplantation (DDLT) using the United Network for Organ Sharing (UNOS) database. For each LDLT recipient (n = 764), two DDLT recipients (n = 1,470), matched for age, gender, race, diagnosis, and year of transplantation, were selected from the UNOS data after excluding multiple organ transplantation or retransplantation, children, and those with incomplete data. Despite our matching, recipients of LDLT had more stable liver disease, as shown by fewer patients with UNOS status 1 or 2A, in an intensive care unit, or on life support. Creatinine and cold ischemia time were also lower in the LDLT group. Primary graft nonfunction, hyperacute rejection rates, and patient survival by Kaplan-Meier analysis were similar in both groups (2-year survival was 79.0% in LDLT vs. 80.7% in case-controls; P = .5), but graft survival was significantly lower in LDLT (2-year graft survival was 64.4% vs. 73.3%; P < .001). Cox regression (after adjusting for confounding variables) analysis showed that LDLT recipients were 60% more likely to lose their graft compared to DDLT recipients (hazard ratio [HR] 1.6; confidence interval 1.1-2.5). Among hepatitis C virus (HCV) patients, LDLT recipients showed lower graft survival when compared to those who received DDLT. In conclusion, short-term patient survival in LDLT is similar to that in the DDLT group, but graft survival is significantly lower in LDLT recipients. LDLT is a reasonable option for patients who are unlikely to receive DDLT in a timely fashion.
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PMID:Graft and patient survival after adult live donor liver transplantation compared to a matched cohort who received a deceased donor transplantation. 1566 72

Oxidative stress is a major pathogenetic event occurring in several liver disorders ranging from metabolic to proliferative ones, and is a major cause of liver damage due to Ischemia/Reperfusion (I/R) during liver transplantation. The main sources of ROS are represented by mitochondria and cytocrome P450 enzymes in the hepatocyte, by Kupffer cells and by neutrophils. Cells are provided with efficient molecular strategies to strictly control the intracellular ROS level and to maintain the balance between oxidant and antioxidant molecules. A cellular oxidative stress condition is determined by an imbalance between the generation of ROS and the antioxidant defense capacity of the cell and can affect major cellular components including lipids, proteins and DNA. Proteins are very important signposts of cellular redox status and through their structure/function modulation, ROS can also influence gene expression profile by affecting intracellular signal transduction pathways. While several enzymatic (such as superoxide dismutase, catalase, glutathione peroxidase) and non enzymatic (such as 4-hydroxynonenal, decrease of glutathione, vitamin E, vitamin C, malondialdehyde) markers of chronic oxidative stress in liver are well known, early protein targets of oxidative injury are yet not well defined. Identification of these markers will enable early detection of liver diseases and will allow monitoring the degree of liver damage, the response to pharmacological therapies and the development of new therapeutic approaches. In the new era of molecular medicine, new proteomics methodologies promise to establish a relationship between pathological hallmarks of disease and protein structural and functional abnormalities in liver disease, thus allowing a better understanding and a more rational therapy on these disorders.
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PMID:The importance of redox state in liver damage. 1550 92

No long-term (>3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) has been reported. This is a prospective, IRB approved, 6-year comparison of A2ALLTx to ADDLTx. Data include: age, gender, ethnicity, primary liver disease, waiting time, pretransplant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications. In 6 years, 202 ADDLTx (74.5%) and 69 A2ALLTx (25.5%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (48.1% vs. 42%). Data regarding overall patient and graft survival, monetary charges and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (11.5% vs. 23.9%) and more biliary complications (26.1% vs. 11.4%). Overall, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.
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PMID:Adult living donor versus deceased donor liver transplantation: a 6-year single center experience. 1563 24

Nonalcoholic fatty liver disease (NAFLD) is consistently associated with features of the metabolic syndrome, a condition carrying a high risk of cardiovascular events. We measured the vasodilatory response of the brachial artery in response to ischemia (a test of endothelial function) (FMV) as well as cardiovascular risk profile in 52 NAFLD cases and 28 age- and sex-matched controls. The 10-year risk of coronary events was calculated according to the Framingham equation and the scores derived from the PROCAM study and NCEP-ATPIII proposals. FMV was 6.33% +/- 5.93% in NAFLD versus 12.22% +/- 5.05% in controls (P < .0001), and higher in pure fatty liver (9.93%) compared with nonalcoholic steatohepatitis (4.94%) (P = .010). No differences were observed in flow-independent vasodilation (response to sublingual nitroglycerin). Percent FMV was negatively associated with insulin resistance (homeostasis model assessment) in the whole population (r = -0.243; P = .030). In logistic regression analysis, NAFLD was associated with a percent FMV in the lower tertile (OR, 6.7; 95% CI, 1.26-36.1), after adjustment for age, sex, body mass index, and insulin resistance. Among NAFLD patients, low FMV was associated with nonalcoholic steatohepatitis (adjusted OR, 6.8; 95% CI, 1.2-40.2). The 10-year probability of cardiovascular events was moderately increased in NAFLD, and particularly in nonalcoholic steatohepatitis. In conclusion, our study provides evidence of endothelial dysfunction and increased risk of cardiovascular events in NAFLD. The risk of advanced liver disease is well recognized in NAFLD patients, but the large majority of cases might experience cardiovascular disease in the long term, indirectly limiting the burden of liver failure.
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PMID:Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. 1617 89

The liver is continuously exposed to a large antigenic load that includes pathogens, toxins, tumor cells and dietary antigens. Amongst the hepatitis viruses, only hepatitis B virus (HBV) and hepatitis C virus (HCV) cause chronic hepatitis, which can progress to cirrhosis and hepatocellular carcinoma. Of the different antiviral defense systems employed by the tissue, apoptosis significantly contributes to the prevention of viral replication, dissemination, and persistence. Loss of tolerance to the liver autoantigens may result in autoimmune hepatitis (AIH). This review outlines the recent findings that highlight the role and mechanisms of apoptotic processes in the course of liver diseases. Among factors that contribute to liver pathology, we discuss the role of tumor necrosis factor (TNF)-alpha, HBx, ds-PKR, TRAIL, FasL, and IL-1alpha. Since TNF and FasL-induced hepatocyte apoptosis is implicated in a wide range of liver diseases, including viral hepatitis, alcoholic hepatitis, ischemia/reperfusion liver injury, and fulminant hepatic failure, these items will be discussed in greater detail in this review. We also highlight some recent discoveries that pave the way for the development of new therapeutic strategies by protecting hepatocytes (for example by employing Bcl-2, Bcl-XL or A1/Bfl-1, IAPs, or synthetic caspase inhibitors), or by the induction of apoptosis in stellate cells. The assessment of the severity of liver disease, as well as monitoring of patients with chronic liver disease, remains a major challenge in clinical hepatology practice. Therefore, a separate chapter is devoted to a novel cytochrome c-based method useful for the diagnosis and monitoring of fulminant hepatitis.
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PMID:Apoptosis in liver diseases--detection and therapeutic applications. 1625 9

Oxidative stress is implicated in the pathogenesis of hepatic ischemia-reperfusion injury, a major determinant of initial poor graft function (IPGF) after orthotopic liver transplantation (OLT). We prospectively investigated the association between the recipient plasma preoperative oxidative stress and the occurrence of IPGF after deceased-donor OLT and indirectly studied the source-hepatic or extra-hepatic-of systemic oxidative stress in vivo in cirrhosis. We used a recently developed specific and sensitive mass spectrometry assay to measure 7beta-hydroxycholesterol and 7-ketocholesterol (oxysterols), markers of oxidative stress, in biological matrices. At univariate analysis, preoperative recipient 7beta-hydroxycholesterol plasma concentration was significantly higher in transplants with subsequent IPGF (n = 9) compared with those with initial good graft function (IGGF; n = 23) [mean +/- SD: 30.63 +/- 26.42 and 11.57 +/- 15.76 ng/mL, respectively] (P = 0.017). In a logistic regression model, which included also the Model for End-Stage Liver Disease (MELD) score, 7beta-hydroxycholesterol plasma concentration was an independent predictor of IPGF with an odds ratio of 1.17 (95% CI, 1.02-1.33, P = 0.028). Patients with cirrhosis (n = 32) had increased oxysterol plasma levels compared with healthy controls (n = 49); livers with cirrhosis (n = 21), however, had oxysterol content comparable with normal livers obtained from organ donors (n = 19). Oxysterols persisted elevated in plasma 1 month after OLT (n = 23). In conclusion, cirrhosis presents upregulated systemic oxidative stress likely of extrahepatic source that is associated with graft failure after OLT.
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PMID:High preoperative recipient plasma 7beta-hydroxycholesterol is associated with initial poor graft function after liver transplantation. 1625 53

Despite a detailed understanding of their metabolism, mitochondria often behave anomalously. In particular, global suppression of mitochondrial metabolism and metabolite exchange occurs in apoptosis, ischemia and anoxia, cytopathic hypoxia of sepsis and multiple organ failure, alcoholic liver disease, aerobic glycolysis in cancer cells (Warburg effect) and unstimulated pancreatic beta cells. Here, we propose that closure of voltage-dependent anion channels (VDAC) in the mitochondrial outer membrane accounts for global mitochondrial suppression. In anoxia, cytopathic hypoxia and ethanol treatment, reactive oxygen and nitrogen species, cytokines, kinase cascades and increased NADH act to inhibit VDAC conductance and promote selective oxidation of membrane-permeable respiratory substrates like short chain fatty acids and acetaldehyde. In cancer cells, highly expressed hexokinase binds to and inhibits VDAC to suppress mitochondrial function while stimulating glycolysis, but an escape mechanism intervenes when glucose-6-phosphate accumulates and dissociates hexokinase from VDAC. Similarly, glucokinase binds mitochondria of insulin-secreting beta cells, possibly blocking VDAC and suppressing mitochondrial function. We propose that glucose metabolism leads to glucose-6-phosphate-dependent unbinding of glucokinase, relief of VDAC inhibition, release of ATP from mitochondria and ATP-dependent insulin release. In support of the overall proposal, ethanol treatment of isolated rat hepatocytes inhibited mitochondrial respiration and accessibility to adenylate kinase in the intermembrane space, effects that were overcome by digitonin permeabilization of the outer membrane. Overall, these considerations suggest that VDAC is a dynamic regulator, or governator, of global mitochondrial function both in health and disease.
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PMID:Voltage-dependent anion channel (VDAC) as mitochondrial governator--thinking outside the box. 1630 70


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