Hepatocellular carcinoma (HCC) represents one of the most common neoplasms worldwide. Surgical resection and local ablative therapies represent the most frequent first lines therapies adopted when liver transplantatio...Hepatocellular carcinoma (HCC) represents one of the most common neoplasms worldwide. Surgical resection and local ablative therapies represent the most frequent first lines therapies adopted when liver transplantation can not be offered or is not immediately accessible. Hepatic resection (HR) is currently considered the most curative strategy, but in the last decade local ablative therapies have started to obtain satisfactory results in term of efficacy and, of them, radiofrequency ablation (RFA) is considered the reference standard. An extensive literature review, from the year 2000, was performed, focusing on results coming from studies that directly compared HR and RFA. Qualities of the studies, characteristics of patients included, and patient survival and recurrence rates were analyzed. Except for three randomized controlled trials (RCT), most studies are affected by uncertain methodological approaches since surgical and ablated patients represent different populations as regards clinical and tumor features that are known to affect prognosis. Unfortunately, even the available RCTs report conflicting results. Until further evidences become available, it seems reasonable to offer RFA to very small HCC (< 2 cm) with no technical contraindications, since in this instance complete necrosis is most likely to be achieved. In larger nodules, namely > 2 cm and especially if > 3 cm, and/or in tumor locations in which ablation is not expected to be effective or safe, surgical removal is to be preferred.展开更多
Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of sever...Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.展开更多
Hepatocellular carcinoma(HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with liver cirrhosis.Liver resection is considered the most potentially curative therapy for HCC patient...Hepatocellular carcinoma(HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with liver cirrhosis.Liver resection is considered the most potentially curative therapy for HCC patients when liver transplantation is not an option or is not immediately accessible.This review is aimed at investigating the current concepts that drive the surgical choice in the treatment of HCC in cirrhotic patients;Eastern and Western perspectives are highlighted.An extensive literature review of the last two decades was performed,on topics covering various aspects of hepatic resection.Early post-operative and long-term outcome measures adopted were firstly analyzed in an attempt to define an optimal standardization useful for research comparison.The need to avoid the development of post-hepatectomy liver failure represents the "conditio sine qua non" of surgical choice and the role of the current tools available for the assessment of liver function reserve were investigated.Results of hepatic resection in relationship with tumor burden were compared with those of available competing strategies,namely,radiofrequency ablation for early stages,and trans-arterial chemoembolization for intermediate and advanced stages.Finally,the choice for anatomical versus non-anatomical,as well as the role of laparoscopic approach,was overviewed.The literature review suggests that partial hepatectomy for HCC should be considered in the context of multi-disciplinary evaluation of cirrhotic patients.Scientific research on HCC has moved,in recent years,from surgical therapy toward non-surgical approaches and most of the literature regarding topics debated in the present review is represented by observational studies,whereas very few well-designed randomized controlled trials are currently available;thus,no robust recommendations can be derived.展开更多
Hepatic encephalopathy(HE)is a neuropsychiatric complex syndrome,ranging from subtle behavioral abnormalities to deep coma and death.Hepatic encephalopathy emerges as the major complication of acute or chronic liver f...Hepatic encephalopathy(HE)is a neuropsychiatric complex syndrome,ranging from subtle behavioral abnormalities to deep coma and death.Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure.Multiplicity of factors are involved in its pathophysiology,such as central and neuromuscular neurotransmission disorder,alterations in sleep patterns and cognition,changes in energy metabolism leading to cell injury,an oxidative/nitrosative state and a neuroinflammatory condition.Moreover,in acute HE,a condition of imminent threat of death is present due to a deleterious astrocyte swelling.In chronic HE,changes in calcium signaling,mitochondrial membrane potential and long term potential expression,N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations,and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed.The main molecule indicated as responsible for all these changes in HE is ammonia.There is no doubt that ammonia,a neurotoxic molecule,triggers or at least facilitates most of these changes.Ammonia plasma levels are increased two-to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite,glutamine(GLN),lead to hyperammonemic conditions.Removal of hepatic ammonia is a differentiated work that includes the hepatocyte,through the urea cycle,converting ammonia into GLN via glutamine synthetase.Under pathological conditions,such as liver damage or liver blood bypass,the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered.This editorial will focus on issues where, to the best of our knowledge,more research is needed in order to clarify,at least partially,controversial topics.展开更多
基金Supported by A speaker fee from Siemens, research contracts with Esaote and advisory board and speaker fee from Bayer to Fabio Piscaglia
文摘Hepatocellular carcinoma (HCC) represents one of the most common neoplasms worldwide. Surgical resection and local ablative therapies represent the most frequent first lines therapies adopted when liver transplantation can not be offered or is not immediately accessible. Hepatic resection (HR) is currently considered the most curative strategy, but in the last decade local ablative therapies have started to obtain satisfactory results in term of efficacy and, of them, radiofrequency ablation (RFA) is considered the reference standard. An extensive literature review, from the year 2000, was performed, focusing on results coming from studies that directly compared HR and RFA. Qualities of the studies, characteristics of patients included, and patient survival and recurrence rates were analyzed. Except for three randomized controlled trials (RCT), most studies are affected by uncertain methodological approaches since surgical and ablated patients represent different populations as regards clinical and tumor features that are known to affect prognosis. Unfortunately, even the available RCTs report conflicting results. Until further evidences become available, it seems reasonable to offer RFA to very small HCC (< 2 cm) with no technical contraindications, since in this instance complete necrosis is most likely to be achieved. In larger nodules, namely > 2 cm and especially if > 3 cm, and/or in tumor locations in which ablation is not expected to be effective or safe, surgical removal is to be preferred.
基金Supported by Fondo de Investigación Sanitaria,Spain (Grant PI070788)CIBERehd is funded by Instituto de la Salud Carlos Ⅲ,Spain
文摘Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.
文摘Hepatocellular carcinoma(HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with liver cirrhosis.Liver resection is considered the most potentially curative therapy for HCC patients when liver transplantation is not an option or is not immediately accessible.This review is aimed at investigating the current concepts that drive the surgical choice in the treatment of HCC in cirrhotic patients;Eastern and Western perspectives are highlighted.An extensive literature review of the last two decades was performed,on topics covering various aspects of hepatic resection.Early post-operative and long-term outcome measures adopted were firstly analyzed in an attempt to define an optimal standardization useful for research comparison.The need to avoid the development of post-hepatectomy liver failure represents the "conditio sine qua non" of surgical choice and the role of the current tools available for the assessment of liver function reserve were investigated.Results of hepatic resection in relationship with tumor burden were compared with those of available competing strategies,namely,radiofrequency ablation for early stages,and trans-arterial chemoembolization for intermediate and advanced stages.Finally,the choice for anatomical versus non-anatomical,as well as the role of laparoscopic approach,was overviewed.The literature review suggests that partial hepatectomy for HCC should be considered in the context of multi-disciplinary evaluation of cirrhotic patients.Scientific research on HCC has moved,in recent years,from surgical therapy toward non-surgical approaches and most of the literature regarding topics debated in the present review is represented by observational studies,whereas very few well-designed randomized controlled trials are currently available;thus,no robust recommendations can be derived.
文摘Hepatic encephalopathy(HE)is a neuropsychiatric complex syndrome,ranging from subtle behavioral abnormalities to deep coma and death.Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure.Multiplicity of factors are involved in its pathophysiology,such as central and neuromuscular neurotransmission disorder,alterations in sleep patterns and cognition,changes in energy metabolism leading to cell injury,an oxidative/nitrosative state and a neuroinflammatory condition.Moreover,in acute HE,a condition of imminent threat of death is present due to a deleterious astrocyte swelling.In chronic HE,changes in calcium signaling,mitochondrial membrane potential and long term potential expression,N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations,and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed.The main molecule indicated as responsible for all these changes in HE is ammonia.There is no doubt that ammonia,a neurotoxic molecule,triggers or at least facilitates most of these changes.Ammonia plasma levels are increased two-to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite,glutamine(GLN),lead to hyperammonemic conditions.Removal of hepatic ammonia is a differentiated work that includes the hepatocyte,through the urea cycle,converting ammonia into GLN via glutamine synthetase.Under pathological conditions,such as liver damage or liver blood bypass,the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered.This editorial will focus on issues where, to the best of our knowledge,more research is needed in order to clarify,at least partially,controversial topics.
