Nikolaos Arkadopoulos

Vascular control during hepatectomy : Review of methods and results

The various techniques of hepatic vascular control are presented, focusing on the indications and drawbacks of each. Retrospective and prospective clinical studies highlight aspects of the pathophysiology, indications, and morbidity of the various techniques of hepatic vascular control. Newer perspectives on the field emerge from the introduction of ischemic preconditioning and laparoscopic hepatectomy. A literature review based on computer searches in Index Medicus and PubMed focuses mainly on prospective studies comparing techniques and large retrospective ones. All methods of hepatic vascular control can be applied with minimal mortality by experienced surgeons and are effective for controlling bleeding. The Pringle maneuver is the oldest and simplest of these methods and is still favored by many surgeons. Intermittent application of the Pringle maneuver and hemihepatic occlusion or inflow occlusion with extraparenchymal control of major hepatic veins is particularly indicated for patients with abnormal parenchyma. Total hepatic vascular exclusion is associated with considerable morbidity and hemodynamic intolerance in 10% to 20% of patients. It is absolutely indicated only when extensive reconstruction of the inferior vena cava (IVC) is warranted. Major hepatic veins/ and limited IVC reconstruction has been also achieved under inflow occlusion with extraparenchymal control of major hepatic veins or even using the intermittent Pringle maneuver. Ischemic preconditioning is strongly recommended for patients younger than 60 years and those with steatotic livers. Each hepatic vascular control technique has its place in liver surgery, depending on tumor location, underlying liver disease, patient cardiovascular status, and, most important, the experience of the surgical and anesthesia team.

Anesthetic and perioperative management of adult transplant recipients in nontransplant surgery.

E ach year, .16,000 patients receive whole organ transplants in the United States alone, and this number is expected to increase yearly (1). Because the 1-yr survival rate for most transplant recipients is approaching 80%–90% and continues to improve annually, an increasing number of patients who received a transplant present for either elective or emergency nontransplant surgery (2–4). Therefore, anesthesiologists and surgeons are often required to manage transplant recipients in hospitals that are not otherwise involved in transplantation procedures. The general considerations related to any transplant recipient are the physiological and pharmacological problems of allograft denervation, the side effects of immunosuppression, the risk of infection, and the potential for rejection.

Global Consequences of Liver Ischemia/Reperfusion Injury

Liver ischemia/reperfusion injury has been extensively studied during the last decades and has been implicated in the pathophysiology of many clinical entities following hepatic surgery and transplantation. Apart from its pivotal role in the pathogenesis of the organs post reperfusion injury, it has also been proposed as an underlying mechanism responsible for the dysfunction and injury of other organs as well. It seems that liver ischemia and reperfusion represent an event with “global” consequences that influence the function of many remote organs including the lung, kidney, intestine, pancreas, adrenals, and myocardium among others. The molecular and clinical manifestation of these remote organs injury may lead to the multiple organ dysfunction syndrome, frequently encountered in these patients. Remote organ injury seems to be in part the result of the oxidative burst and the inflammatory response following reperfusion. The present paper aims to review the existing literature regarding the proposed mechanisms of remote organ injury after liver ischemia and reperfusion.

Long chain versus medium chain lipids in patients with ARDS : effects on pulmonary haemodynamics and gas exchange

Objective: To compare pulmonary haemodynamic and gas exchange alterations in septic patients with ARDS receiving long-chain triglycerides (LCT) versus medium-chain triglycerides (MCT). Design: Prospective, randomised, clinical study. Setting: Surgical ICU patients in a University Hospital. Patients: Twenty-one septic patients with ARDS were randomly assigned to receive 50 % of their non-protein caloric requirements as either 20 % LCT (group 1, n = 10) or 20 % 1 : 1 mixture of LCT/MCT (group 2, n = 11). Intervention: Intravenous infusion of LCT and LCT/MCT combinations at a rate of 12 g · h− 1. Measurements and results: The LCT infusion was associated with an increase of pulmonary venous admixture (Qva/Qt) from 24 % ± 5 % to 37 % ± 6 %, an increase of mean pulmonary artery pressure (MPAP) from 25 ± 5 to 33 ± 4 mmHg and decrease of PaO2/FIO2 from 240 ± 30 to 180 ± 35. LCT/MCT administration was only associated with an elevation of oxygen consumption (VO2) from 329 ± 14 to 396 ± 12 ml/min. During lipid infusion group 1 patients presented higher Qva/Qt (37 % ± 6 % vs 25 % ± 4 %), MPAP (33 ± 4 vs 27 ± 3 mmHg) and VO2 (359 ± 11 vs 396 ± 12 ml/min) and lower PaO2/FIO2 (180 ± 35 vs 235 ± 30) values compared to group 2. Conclusion: In conclusion, we have shown that, in septic patients with respiratory failure, LCT administration was associated with more significant changes of Qva/Qt, MPAP and PaO2/FIO2 compared to infusion of an LCT/MCT 1 : 1 emulsion. Clinically, these transient alterations might cause serious problems in patients with marginal arterial oxygenation and cardio-respiratory impairment.

Pathways and targets in hepatocellular carcinoma

The incidence of hepatocellular carcinoma (HCC) has been rising in several western low-incidence areas over the past decade. The purpose of this review was to summarize the current knowledge on the ‘state of the art’ management of HCC focusing on targeted systemic therapies. The information for this review was compiled by searching the PubMed and MEDLINE databases for articles published until 1 June 2012. Cytotoxic chemotherapy has failed to affect outcome of HCC. Treatment with sorafenib is associated with survival gain in HCC but the responses are not durable. In addition, sorafenib is associated with substantial dermatologic and gastrointestinal toxicity. In this review, the authors summarize molecular targets and signal transduction pathways in HCC and provide an update of published and ongoing studies. Many targeted agents against angiogenesis, Ras/Raf/MAPK, EGF receptor, PI3K/AKT/mTOR, HGF/Met and IGF/IGF receptor are being tested in clinical trials.

Ischemia/reperfusion injury in liver resection: a review of preconditioning methods.

Ischemic preconditioning is one of the therapeutic interventions aiming at preventing ischemia/reperfusionrelated injury. Numerous experimental studies and a few clinical series have shown that during liver resections, ischemic preconditioning is a promising strategy for optimizing the postoperative outcome. Moreover, various types of pharmacological intervention as well as different types of preconditioning, such as remote preconditioning, the use of heat shock, and hyperbaric oxygen, have been developed to attenuate the functional impairment accompanying ischemia/reperfusion injury. This review summarizes the various forms of preconditioning, thus suggesting that close cooperation between surgeons and anesthesiologists paves the way to apply novel strategies to improve the outcome of liver resection.

Pancreatic leakage after pancreaticoduodenectomy: the impact of the isolated jejunal loop length and anastomotic technique of the pancreatic stump.

Objectives To evaluate the impact of the length of the isolated jejunal loop and the type of pancreaticojejunostomy on pancreatic leakage after pancreaticoduodenectomy. Methods One hundred thirty-two consecutive patients who underwent a pancreaticoduodenectomy were studied according to the length of the isolated jejunal loop (short loop, 20-25 cm vs long loop, 40-50 cm) and the type of pancreaticojejunostomy (invagination vs duct to mucosa). Results The use of the long isolated jejunal loop was associated with a significantly lower pancreatic leakage rate compared with the use of a short isolated jejunal loop (4.34% vs 14.2%, P < 0.05). In addition, the use of duct-to-mucosa technique was associated with significantly lower incidence of postoperative pancreatic fistula compared with the invagination technique (4.2% vs 14.5%, P < 0.05). Finally, patients with a short isolated jejunal loop compared with patients with a long loop had increased morbidity (50.7% vs 27.5%, P < 0.05) and prolonged hospital stay (16.3 ± 1.9 days vs 10.2 ± 2.3 days, P < 0.05). Overall mortality rate was 1.5%. Conclusions The use of a long isolated jejunal loop and a duct-to-mucosa pancreaticojejunostomy is associated with decreased pancreatic leakage rate after pancreaticoduodenectomy.

Effect of mesocaval shunt on survival of small-for-size liver grafts: Experimental study in pigs

Segmental liver grafts with a calculated ideal liver weight (CILW) less than 40% may be associated with portal flow-related injuries and primary dysfunction. This study evaluated the effect of mesocaval shunts on the survival of grafts with a CILW less than 20%. Sixteen pigs underwent orthotopic transplantation of segmental liver grafts with a CILW less than 20%. In eight animals (study group), transplantation was combined with a mesocaval shunt, and eight animals served as controls without a mesocaval shunt. Liver function, systemic hemodynamics, portal vein pressure, intracranial pressure, and cerebral perfusion pressure were assessed postoperatively. The controls showed a rapid impairment of liver function reflected by a significant elevation in aspartate aminotransferase, international normalized ratio, bilirubin, and intracranial pressure and a decrease in cerebral perfusion pressure compared with the study group (P <0.05). Mesocaval shunts showed protective effects on grafts with CILW less than 20% and may have a clinical role in the salvage of small-for-size liver grafts.

Development of a Porcine Model of Post-Hepatectomy Liver Failure

BACKGROUND The aim of this study was to develop a porcine model of post-operative liver failure (POLF) that could accurately reproduce all the neurological and metabolic parameters of the corresponding clinical syndrome that may develop after extensive liver resections. METHODS In our model, we induced POLF by combining extended left hepatectomy and ischemia of the small liver remnant of 150 min duration. Subsequently, the remnant liver parenchyma was reperfused and the animals were closely monitored for 24 h. MATERIALS Twelve Landrace pigs (weight 25-30 kg) were randomly assigned in two groups; eight of them constituted the experimental group, in which POLF was induced (POLF group, n = 8), whereas the rest of them (n = 4) were included in the control group (sham laparotomy without establishment of POLF). RESULTS (MEANS ± SD): All POLF animals gradually developed neurological and biochemical signs of liver failure including, among many other parameters, elevated intracranial pressure (24.00 ± 4.69 versus 10.17 ± 0.75, P = 0.004) and ammonia levels (633.00 ± 252.21 versus 51.50 ± 9.49, P = 0.004) compared with controls. Histopathologic evaluation of the liver at the end of the experiment demonstrated diffuse coagulative necrosis and severe architectural distortion of the hepatic parenchyma in all POLF animals. CONCLUSION Our surgical technique creates a reproducible porcine model of POLF which can be used to study the pathophysiology and possible therapeutic interventions in this serious complication of extensive hepatectomies.

IRON CHELATION FOR AMELIORATION OF LIVER ISCHEMIA-REPERFUSION INJURY

Liver resections are frequently associated with significant ischemia-reperfusion (I-R) injury of the liver remnant. The aim of this study was to investigate whether deferoxamine (DFO) can ameliorate I-R injury during major hepatectomies performed under vascular exclusion of the liver in a porcine model. Twelve female domestic pigs were divided into control (n = 6) and DFO treatment (n = 6) groups and subjected to 150 min. liver ischemia followed by 70% hepatectomy and 24 hours reperfusion. Pigs in the DFO group received a continuous intravenous infusion of 100 mg/kg DFO. Liver remnant injury was evaluated by liver function tests, hepatic histology as well as serum and liver tissue malondialdehyde (MDA) concentrations. Deferoxamine-treated animals had reduced total bilirubin, γ-glutamyl transferase and ammonia levels as well as hepatocyte necrosis and oxidative injury. In a subsequent randomized clinical trial using DFO for I-R protection during major liver surgery, preliminary results revealed amelioration of hepatocellular damage, oxidative and inflammatory serum markers and apoptotic response in liver remnant biopsies.