Pharmacokinetics of the antimicrobial drug Sulfanilamide is altered in a preclinical model of vascular calcification.

In vascular smooth muscle, calcium overload is linked to advancing age. The pharmacokinetics of Sulfanilamide (SA), a compound with antibacterial properties, was evaluated in a preclinical model of vascular calcification. SA was used since it is useful to study possible modifications in the renal and hepatic management of drugs. Vascular calcification was induced by administration of a single high dose of vitamin D3 to rats (treated group) 10 days before the experiments. A parallel control group was processed. The decrease of renal blood flow due to calcification of the renal arteries explains, at least in part, the decrease in the renal clearance of SA observed in treated rats. The liver metabolic function increased in treated rats as demonstrated by increases in plasma appearance rate of acetylated-Sulfanilamide (ASA), hepatic ASA content and hepatic N-acetyltransferase activity. The decrease in renal excretion of SA was not completely compensated by the hepatic metabolism increase, since the elimination rate of SA from the central compartment (K1-0 ) decreased in the treated group. In summary, in this experimental model with sustained arterial calcinosis induced by a single high dose of vitamin D3 10 days before the experiments, the pharmacokinetics of an aminobenzenesulfonamide is modified, at least in part, by the increase in the activity of hepatic N-acetyltransferase and the decrease in renal blood flow. This study emphasizes the importance of considering the presence of vascular calcification when a drug dose scheme is performed, in order to optimize pharmacotherapeutic results.

Preclinical Assessment of the Efficacy of Anti-Angiogenic Therapies in Hepatocellular Carcinoma.

Diffuse hepatocellular carcinoma (HCC) is a complex affliction in which comorbidities can bias global outcome of cancer therapy. Better methods are thus warranted to directly assess effects of therapy on tumor angiogenesis and growth. As tumor angiogenesis is invariably associated with changes in local blood flow, we assessed the utility of ultrasound imaging in evaluation of the efficacy of anti-angiogenic therapy in a spontaneous transgenic mouse model of HCC. Blood flow velocities were measured monthly in the celiac trunk before and after administration of sorafenib or bevacizumab at doses corresponding to those currently used in clinical practice. Concordant with clinical experience, sorafenib, but not bevacizumab, reduced microvascular density and suppressed tumor growth relative to controls. Evolution of blood flow velocities correlated with microvascular density and with the evolution of tumor size. Ultrasound imaging thus provides a useful non-invasive tool for preclinical evaluation of new anti-angiogenic therapies for HCC.

Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation

This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation.

This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

Protective Effect of Nitric Oxide on Liver Circulation from Ischemia Reperfusion Injury.

INTRODUCTION: The reduction of endogenous nitric oxide (NO) production during hepatic ischemia-reperfusion injury, generally via a reduction in endothelial NO synthase activity, leads to liver injury. We hypothesized that administration of an exogenous NO donor into the portal vein may ameliorate hepatic blood flow reduction after a period of ischemia. MATERIAL AND METHODS: A total of 90 min of ischemia (portal vein and hepatic artery) was applied in 15 anesthetized pigs, using the Pringle method under sevoflurane anesthesia. All animals were administered either saline (control group, n = 8) or sodium nitroprusside (SNP, n = 7) as exogenous NO donor drugs into the portal vein, 30 min before and after ischemia. The portal venous blood flow and hepatic artery blood flow were measured continuously using transonic flow probes attached to each vessel. Endogenous NO (NOx = NO2- + NO3-) production was measured every 10 min using a microdialysis probe placed in the left lobe of the liver. RESULTS: In the SNP group, portal venous flow remained unchanged and hepatic artery flow significantly increased compared to baseline. Although the production of liver tissue NOx transiently decreased to 60% after ischemia, its level in the SNP group remained higher than the control saline group. CONCLUSION: Regional administration of SNP into the portal vein increases hepatic arterial flow during ischemia reperfusion periods without altering mean systemic arterial pressure. We speculate that administration of an exogenous NO donor may be effective in preventing liver injury via preservation of total hepatic blood flow.

Cilostazol improves hepatic blood perfusion, microcirculation, and liver regeneration after major hepatectomy in rats.

Major hepatectomy or small-for-size liver transplantation may result in postoperative liver failure. So far, no treatment is available to improve liver regeneration. Herein, we studied whether cilostazol, a selective phosphodiesterase III inhibitor, is capable of improving liver regeneration after major hepatectomy. Sprague-Dawley rats (n = 74) were treated with cilostazol (5 mg/kg daily) or a glucose solution and underwent either 70% liver resection or a sham operation. Before and after surgery, hepatic arterial and portal venous blood flow and hepatic microvascular perfusion were analyzed. Liver morphology, function, and regeneration were studied with histology, immunohistochemistry, western blotting, and bile excretion analysis. Cilostazol significantly increased hepatic blood flow and microcirculation before and after hepatectomy in comparison with sham-operated controls. This was associated with an elevation of hepatic vascular endothelial growth factor expression, an increase of hepatocellular proliferation, and an acceleration of liver regeneration. Furthermore, cilostazol protected the tissue of the remnant liver as indicated by an attenuation of hepatocellular disintegration. In conclusion, cilostazol increases hepatic blood perfusion, microcirculation, and liver regeneration after a major hepatectomy. Thus, cilostazol may represent a novel strategy to reduce the rate of liver failure after both extended hepatectomy and small-for-size liver transplantation.

Decreased blood flow after sorafenib administration is an imaging biomarker to predict overall survival in patients with advanced hepatocellular carcinoma.

BACKGROUND: Sorafenib is a multikinase inhibitor targeting Raf and protein tyrosine kinases, which are involved in cell growth and tumor angiogenesis. Sorafenib administration induces temporary inhibition of tumor growth and a decrease in arterial blood flow in a considerable number of hepatocellular carcinoma (HCC) patients. We retrospectively evaluated the association between decreased blood flow and the overall survival (OS) of HCC patients after the initiation of sorafenib therapy. PATIENTS AND METHODS: Therapeutic responses of 158 advanced HCC patients with hypervascular tumors who had received sorafenib for more than 1 month were analyzed. To assess their therapeutic response, patients underwent radiological evaluation before and every 4-6 weeks after the initiation of sorafenib treatment. After the classification of patients into three groups based on the change in arterial enhancement during treatment (no change, decrease and disappearance), the OS of each group was compared using the Kaplan-Meier method. RESULTS: Statistically significant differences in OS were observed among the three groups (p < 0.001). A decrease or disappearance of arterial enhancement was significantly associated with improved OS compared to patients with no change in arterial enhancement; the median OS was 19.9 months (95% confidence interval, CI, 16.4-24.5 months) and 6.0 months (95% CI, 4.0-8.8 months), respectively (p < 0.001). However, there was no difference in OS between the decrease and disappearance groups (p = 0.88). CONCLUSION: We conclude that decreased arterial enhancement during sorafenib treatment was associated with the longest OS and could therefore reflect an effective response.

Is it tea time for portal hypertension?

Portal hypertension is the main complication of cirrhosis and represents a leading cause of death in patients with chronic liver disease. Therapeutic agents to improve portal hypertension should ameliorate the underlying mechanisms of portal hypertension: the elevated hepatic resistance and the hyperdynamic circulation. In the present issue of Clinical Science, Hsu and co-workers show the beneficial effects of GTPs (green tea polyphenols) in improving portal hypertension. Long-term administration of GTPs inhibited the development of cirrhosis and portal hypertension by decreasing both hepatic resistance and splanchnic hyperdynamic circulation. The main underlying mechanism of the benefits of GTPs appears related to the down-regulation of splanchnic angiogenesis. The present study adds further evidence supporting the potential of natural compounds for an effective nutriceutical approach to the treatment of patients with cirrhosis of the liver.

Green tea polyphenol decreases the severity of portosystemic collaterals and mesenteric angiogenesis in rats with liver cirrhosis.

Abnormal angiogenesis in liver cirrhosis often leads to severe complications such as variceal haemorrhage and encephalopathy. Furthermore, splanchnic angiogenesis elevates portal pressure, in which angiogenic factors play pivotal roles. GTP (green tea polyphenol) extracted from Camellia sinensis has anti-angiogenic properties, but the effects on the parameters described above in cirrhosis have not been investigated. The aim of the present study was to determine the effects of GTP in cirrhosis and to investigate the underlying mechanism. Liver cirrhosis was induced in Spraque-Dawley rats by common BDL (bile duct ligation). They randomly received GTP or DW (distilled water, vehicle) for 28 days, then haemodynamic parameters, portosystemic shunting, mesenteric window vascular density, intrahepatic angiogenesis, liver fibrosis, plasma VEGF (vascular endothelial growth factor) concentration, mesenteric angiogenic factor and receptor protein expression, and serum and mesenteric oxidative stress parameters were assessed. Compared with the DW group, GTP significantly decreased portosystemic shunting, liver fibrosis, intrahepatic angiogenesis, mesenteric window vascular density, VEGF concentration and down-regulated the mesenteric HIF (hypoxia-inducible factor)-1α, VEGF and phospho-Akt expression. In conclusion, GTP ameliorates the severity of portosystemic shunting and mesenteric angiogenesis via the suppression of HIF-1α, Akt activation and VEGF. GTP appears to be an appropriate agent in controlling portal hypertension-related complications via anti-angiogenesis.

PPARγ ligand attenuates portal inflammation in the MRL-lpr mouse: a new strategy to restrain cholangiopathy in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is characterized by chronic destructive cholangitis, which is associated with the reduced expression of an anti-inflammatory molecule, peroxisome proliferator-activated receptor-γ (PPARγ), in intrahepatic bile ducts. We previously demonstrated the anti-inflammatory effects of PPARγ ligands using cultured human biliary epithelial cells. In this study, we evaluated the effectiveness of PPARγ ligand against peribiliary inflammation in vivo. As an animal model of PBC, we used MRL/lpr mice in which a PBC-like cholangitis occurs naturally. Anti-inflammatory effects of the intraperitoneal administration of a PPARγ ligand, the prostaglandin D metabolite 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2), were evaluated. In untreated mice, portal inflammation including cholangitis was found to some degree in the majority of portal tracts. In mice given a high-dose group, the degree of portal inflammation was significantly reduced and mice mostly lacking portal inflammation and cholangitis were also found. T cell numbers in portal tracts were markedly decreased in the high-dose group, compared with controls, whereas there was no significant difference in terms of B cells and macrophages. This study is the first to assess the therapeutic potential of a PPARγ ligand against portal inflammation including cholangitis. Anti-inflammatory effects of PPARγ ligands may prevent the progression of cholangiopathy in PBC patients.

Changes in hepatic blood flow during transcatheter arterial infusion with heated saline in hepatic VX2 tumor.

PURPOSE: This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. METHODS: All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 °C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 °C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. RESULTS: After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. CONCLUSIONS: The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

Methane biogenesis during sodium azide-induced chemical hypoxia in rats.

Previous studies demonstrated methane generation in aerobic cells. Our aims were to investigate the methanogenic features of sodium azide (NaN(3))-induced chemical hypoxia in the whole animal and to study the effects of l-α-glycerylphosphorylcholine (GPC) on endogenous methane production and inflammatory events as indicators of a NaN(3)-elicited mitochondrial dysfunction. Group 1 of Sprague-Dawley rats served as the sham-operated control; in group 2, the animals were treated with NaN(3) (14 mg·kg(-1)·day(-1) sc) for 8 days. In group 3, the chronic NaN(3) administration was supplemented with daily oral GPC treatment. Group 4 served as an oral antibiotic-treated control (rifaximin, 10 mg·kg(-1)·day(-1)) targeting the intestinal bacterial flora, while group 5 received this antibiotic in parallel with NaN(3) treatment. The whole body methane production of the rats was measured by means of a newly developed method based on photoacoustic spectroscopy, the microcirculation of the liver was observed by intravital videomicroscopy, and structural changes were assessed via in vivo fluorescent confocal laser-scanning microscopy. NaN(3) administration induced a significant inflammatory reaction and methane generation independently of the methanogenic flora. After 8 days, the hepatic microcirculation was disturbed and the ATP content was decreased, without major structural damage. Methane generation, the hepatic microcirculatory changes, and the increased tissue myeloperoxidase and xanthine oxidoreductase activities were reduced by GPC treatment. In conclusion, the results suggest that methane production in mammals is connected with hypoxic events associated with a mitochondrial dysfunction. GPC is protective against the inflammatory consequences of a hypoxic reaction that might involve cellular or mitochondrial methane generation.

Live cell-imaging perfusion culture system of liver sinusoidal endothelial cells to mimic stem cell engraftment in liver.

Hepatocyte and various hepatic stem cell transplantations have been studied as alternative therapies to orthotopic liver transplantation for liver injury. The engraftment of transplanted cells into the parenchyma requires transmigration through sinusoidal endothelial cells (SECs), the only cellular barrier. In this study, we constructed a SEC-imaging perfusion culture system that mimics sinusoids with respect to hemorheologic properties. SECs were successfully maintained for 24 hours. Human liver stem cells (HLSCs) were used as a model of transplanted cells for in vitro engraftment to SECs under perfusion culture conditions. Conditions of high shear stress perfusion with 0.34 dyne/cm(2) significantly reduced cell adhesion in contrast to lower shear stress conditions of 0.1 and 0.03 dyne/cm(2). Among the biologic perfusion fluids, namely, fetal bovine serum (FBS), pig plasma, and 5% human albumin solution, HLSCs showed significantly greater attachment to SECs when perfused with FBS, which is well known to contain abundant amounts of adhesion molecules. This biomimetic SEC perfusion culture system may provide a useful tool to study engraftment mechanisms and to evaluate the effects of various enhancers as an alternative to animal models.

Therapeutic potential of pegylated hemin for reactive oxygen species-related diseases via induction of heme oxygenase-1: results from a rat hepatic ischemia/reperfusion injury model.

Many diseases and pathological conditions, including ischemia/reperfusion (I/R) injury, are the consequence of the actions of reactive oxygen species (ROS). Controlling ROS generation or its level may thus hold promise as a standard therapeutic modality for ROS-related diseases. Here, we assessed heme oxygenase-1 (HO-1), which is a crucial antioxidative, antiapoptotic molecule against intracellular stresses, for its therapeutic potential via its inducer, hemin. To improve the solubility and in vivo pharmacokinetics of hemin for clinical applications, we developed a micellar hemin by conjugating it with poly(ethylene glycol) (PEG) (PEG-hemin). PEG-hemin showed higher solubility in water and significantly prolonged plasma half-life than free hemin, which resulted from its micellar nature with molecular mass of 126 kDa in aqueous media. In a rat I/R model, administration of PEG-hemin significantly elevated HO-1 expression and enzymatic activity. This induction of HO-1 led to significantly improved liver function, reduced apoptosis and thiobarbituric acid reactive substances of the liver, and decreased inflammatory cytokine production. PEG-hemin administration also markedly improved hepatic blood flow. These results suggest that PEG-hemin exerted a significant cytoprotective effect against I/R injury in rat liver by inducing HO-1 and thus seems to be a potential therapeutic for ROS-related diseases, including I/R injury.

Correlation between tumor perfusion and lipiodol deposition in hepatocellular carcinoma after transarterial chemoembolization.

PURPOSE: To study the correlation of tumor perfusion with lipiodol deposition in hepatocellular carcinoma (HCC) after transarterial chemoembolization with multidetector computed tomography (MDCT) perfusion imaging. MATERIALS AND METHODS: MDCT perfusion imaging was performed in 24 patients with HCC 1 to 7 days before chemoembolization. The computed tomography (CT) perfusion parameters, such as hepatic arterial perfusion (HAP), hepatic portal perfusion (HPP), total liver perfusion (TLP), and hepatic arterial perfusion index (HAPI), were calculated with the slope method. The follow-up CT scans (noncontrast) were performed 4 weeks after chemoembolization to analyze lipiodol deposition. The lipiodol deposition in the tumor was classified into three grades and compared with CT perfusion parameters before chemoembolization. RESULTS: The HAP and TLP of tumors before chemoembolization were correlated with the grades of lipiodol deposition in tumors after chemoembolization (r = 0.768, P < .0001 and r = 0.616, P = .001, respectively). However, the HPP and HAPI of the tumors were not related to the grades of iodized oil deposition (r = 0.227, P = .286 and r = 0.111, P = .607, respectively). Higher HAP was correlated with better lipiodol deposition, and lower HAP was correlated with poorer lipiodol deposition. CONCLUSIONS: MDCT perfusion imaging has the potential to help select more appropriate patients with HCC for chemoembolization.

[Effects of electroacupuncture on hepatic blood flow and lipid peroxidation in septic rats].

OBJECTIVE: To investigate the protection effects of electroacupuncture on injury of lipid peroxidation induced by liver ischemia in septic rats. METHODS: Forty-eight male SD rats were subjected to sepsis induced by cecal ligation and puncture (CLP), and were randomly divided into a Sham operation group (group A), a CLP model group (group B), a CLP model plus electroacupuncture at "Zusanli" (ST 36) group (group C), a CLP model plus electroacupuncture at the shame acupoint (group D), a vagotomy plus CLP model group (group E) and CLP model plus electroacupuncture group after vagotomy (group F), 8 rats in each group. CLP was performed in group E and group F after the abdominal vagotomy. Bilateral "Zusanli"(ST 36) points and the shame acupoint were electroacupunctured (2 mA, 2/100 Hz) for 1 hour in group C, group F and group D, respectively. The hepatic blood flow (HBF) was detected by a laser-Doppler flowmetry at 6 h after CLP. The plasma activity of alanine aminotransferase (ALT) was also determined and specimens of liver were harvested for evaluation of malondialdehyde (MDA), xanthine oxidase (XOD) and assessment of the rate of water content. RESULTS: The blood flow of the liver was (56.97 +/- 11.95) U in group C which was significantly lower than (80.12 +/- 19.57) U in group A but higher than (42.61 +/- 10.97) U in group B, (44.53 +/- 9.23) U in group D, (30.05 +/- 4.46) U in group E and (30.46 +/- 6.38) U in group F (all P < 0.05) 6 h after CLP. Meanwhile, the levels of MDA, XOD, ALT and the rates of water content in liver in group C were all significantly higher than those in group A, but lower than those in the other four groups (all P < 0.05). The levels of MDA, XOD, ALT and the rates of water content in liver in group E and group F were all significantly higher than those in group D (all P < 0.05), while the blood flow of the liver lower than that in group D (P < 0.05), and with no significant differences in all above measurements between group E and group F (all P > 0. 05). CONCLUSION: Electroacupuncture at "Zusanli" (ST 36) can promote hepatic blood flow, inhibit lipid peroxidation and alleviate hepatic edema and dysfunction in septic rats, which might be related with the completeness of cranial nerve.

Living donor liver transplantation.

PURPOSE OF REVIEW: The widening gap between the growing number of liver transplant candidates and the supply of deceased donor organs became a strong motivation for the development of living donor liver transplantation (LDLT). LDLT has gone through its developmental phase and become an established life-saving procedure. RECENT FINDINGS: Despite the challenging nature of the technique of LDLT, there have been continuous innovations. A better understanding of complex surgical anatomy and physiologic differences of partial hepatic allografts has helped to avoid graft congestion, small-for-size syndrome, or graft hypoperfusion from portal flow steal. LDLT for patients with high Model for End-Stage Liver Disease score can achieve comparable results with deceased donor liver transplantation (DDLT). Size limitation of partial grafts can be overcome with dual grafts. The extended application of LDLT for hepatocellular carcinoma beyond Milan criteria seems feasible but at the cost of slightly compromised survival. More information has become available for prospective donors about the consequences of living liver donation in terms of psychosocial impact. SUMMARY: Although LDLT is still evolving, it has become the most effective alternative to DDLT. Proven or potential benefit of LDLT include the superior quality of the allograft despite the smaller size, selection of proper timing for transplantation and a reduced waiting time, which prevents waiting list mortality.

Building the body: active learning laboratories that emphasize practical aspects of anatomy and integration with radiology.

Active learning exercises were developed to allow advanced medical students to revisit and review anatomy in a clinically meaningful context. In our curriculum, students learn anatomy two to three years before they participate in the radiology clerkship. These educational exercises are designed to review anatomy content while highlighting its relevance to the study of radiology. Laboratory exercises were developed using inexpensive materials in the form of hands-on stations designed for use by students working together in small groups. Station exercises include model building, exploring relevant radiological imaging, and practicing clinical techniques. Students are encouraged to move from abstract conceptualization of the anatomy using models to applying knowledge to living tissues by using a portable ultrasound to explore superficial anatomy on each other. Stations are designed to integrate knowledge and reemphasize concepts in different contexts, so that upon completion students have a reinforced understanding of the three-dimensional anatomy of the region in question, the appearance of the anatomy on radiological images, and an appreciation of the relevance of the anatomy to radiological procedures.

Radiofrequency ablation of liver tumors (II): clinical application and outcomes.

Radiofrequency ablation is one of the alternatives in the management of liver tumors, especially in patients who are not candidates for surgery. The aim of this article is to review applicability of radiofrequency ablation achieving complete tumor destruction, utility of imaging techniques for patients' follow-up, indications for local ablative procedures, procedure-associated morbidity and mortality, and long-term results in patients with different tumors. The success of local thermal ablation consists in creating adequate volumes of tissue destruction with adequate "clear margin," depending on improved delivery of radiofrequency energy and modulated tissue biophysiology. Different volumes of coagulation necrosis are achieved applying different types of electrodes, pulsing energy sources, utilizing sophisticated ablation schemes. Some additional methods are used to increase the overall deposition of energy through alterations in tissue electrical conductivity, to improve heat retention within the tissue, and to modulate tolerance of tumor tissue to hyperthermia. Contrast-enhanced computed tomography, magnetic resonance imaging, ultrasound or positron emission tomography are applied to control the effectiveness of radiofrequency ablation. The long-term results of radiofrequency ablation are controversial.