Bacterial translocation, infection and coagulation in cirrhosis and portal hypertension

non disponibileIn cirrhotic patients there is an increased susceptibility to bacterial infection, related to the degree of liver dysfunction leading to several abnormalities of defense mechanisms, all of which increase the susceptibility to infection, including deficiency of bactericidal and opsonic activities, impaired monocyte function, depressed phagocytic activity of the reticuloendothelial system (RES), defective chemotaxis, and low levels of complement in serum. A particularly important role is played by the reduced RES activity, which is due to the presence of extrahepatic shunts and intrahepatic shunts through sinusoids without Kupffer cells, a reduced number of Kupffer cells, and impaired Kupffer cell function. Thus cirrhotics with impaired RES phagocytic activity (as assessed by the elimination of 99m technetium-sulfur colloid) develop acute bacterial infections more frequently than cirrhotics with normal RES phagocytic activity. Both community and hospital acquired bacterial infections are frequently diagnosed in cirrhotics, the most frequent being spontaneous bacterial peritonitis (SBP), urinary tract infections, pneumonia and skin infections, their incidence increasing with the severity of liver dysfunction. Importantly, half of these episodes may be asymptomatic. Recently bacterial infections and/or endotoxaemia have been associated with failure to control variceal bleeding, more early variceal rebleeding, abnormalities in coagulation, vasodilatation of the systemic vasculature and worsening of liver function. There is an increased recognition that bacterial infections are involved in several pathophysiological abnormalities in cirrhosis, so that in this introduction we aim to evaluate the potential mechanisms and the clinical evidence illustrating the pivotal role of bacterial infection. This could lead to new treatment strategies

In vivo imaging of pancreatic tumours and liver metastases using 7 Tesla MRI in a murine orthotopic pancreatic cancer model and a liver metastases model

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 Tesla MRI and evaluate its clinical relevance and applicability.</p> <p>Methods</p> <p>6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA.</p> <p>Results</p> <p>MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p < 0.01) when comparing calliper measurments (n = 5, mean 1065 mm³+/-243 mm³) with MRI (mean 918 mm³+/-193 mm³) with MRI being more precise. Histology (n = 5) confirmed MRI tumour measurements (mean size MRI 38.5 mm²+/-22.8 mm²versus 32.6 mm²+/-22.6 mm²(histology), p < 0,0004) with differences due to fixation and processing of specimens. After splenic injection all mice developed liver metastases with a mean of 8 metastases and a mean volume of 173.8 mm³+/-56.7 mm³after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p < 0.05) higher than gadolinium-DTPA. All imaging experiments could be done repeatedly to comply with the 3R-principle thus reducing the number of experimental animals.</p> <p>Conclusions</p> <p>This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.</p

An apology for beta blockers

This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text

Beta-blockers in liver cirrhosis

Since the original description of the effectiveness of beta-blockers in lowering the portal pressure and therefore the risk of variceal bleeding, more than 500 articles in the English literature on the use of non selective beta-blockers (NSBB) in cirrhosis have been published. The use of NSBB in pre-primary prophylaxis of variceal bleeding is currently not indicated. In primary prophylaxis, patients with high risk small varices or large/medium varices should receive primary prophylaxis either with NSBB or with endoscopic band ligation if there are contraindications to NSBB. For secondary prophylaxis the current recommendation is to receive a combination of NSBB and endoscopic variceal ligation. In addition to lowering portal pressure, NSBB can also reduce bacterial translocation, potentially exerting multiple beneficial effects which go beyond the reduction of bleeding risk. Carvedilol is a NSBB with intrinsic anti-alpha(1)-adrenergic activity, possibly more effective than propranolol in lowering portal hypertension. A potential harmful effect of propranolol in patients with cirrhosis with refractory ascites deserves further confirmation. NSBB remain the cornerstone of therapy in cirrhotic patients with portal hypertension.This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text