The reduction of portal pressure in patients with early compensated cirrhosis may be more responsive to drugs increasing intrahepatic vasodilatation than those reducing portal venous inflow. The PDE-V inhibitor sildenafil can potentially reduce portal pressure by decreasing intrahepatic resistance, but its systemic vasodilatory effects may be deleterious. Aim:Evaluate the effect of sildenafil on systemic and portal hemodynamics in an open-label pilot study. Methods:Twelve patients with compensated cirrhosis and baseline hepatic venous pressure gradient (HVPG) >5 mmHg received 25mg of oral sildenafil. Mean arterial pressure(MAP), heart rate (HR) and HVPG were repeated after 30 and 60 minutes and in 9/12 patients at 90 minutes (after an additional 25mg of sildenafil). HVPG tracings were read by 3 blinded observers.Results: All 12 patients were Child A with median MAP 92 mm Hg(84-95) and median HVPG 10.4 mmHg(6.6-13.0). While MAP decreased significantly at all time points, sildenafil had no effect on HVPG. Conclusion:As shown with other vasodilators, in compensated cirrhotic patients, sildenafil at therapeutic doses for erectile dysfunction reduces MAP without reducing portal pressure. The search should continue for specific intrahepatic vasodilators. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. KeywordsDisclosures: Dr. Garcia-Tsao is consultant for Dong Pharmaceuticals that makes udenafil (a long-acting PDE-V inhibitor) Portal hypertension is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initially due to increased intrahepatic resistance and subsequently maintained by an increase in portal blood inflow. A reduction in portal pressure results in a lower rate of complications of cirrhosis(1-3).Non-selective beta-blockers (BB) reduce portal pressure by reducing portal venous inflow. Although BB prevent variceal hemorrhage in patients with varices they do not prevent the development of varices(4), perhaps because portal hypertension in patients without varices (early disease) is more dependent on increased intrahepatic resistance than increased portal inflow. Experimental studies have demonstrated that cirrhotic rats without ascites already have impaired intrahepatic vasorelaxation(5).Since portal pressure reduction in patients with early (compensated) cirrhosis is related to a decrease in outcomes(4), pharmacological therapy should be targeted at reducing intrahepatic resistance by increasing intrahepatic nitric oxide (NO). Available vasodilators not only reduce intrahepatic resistance but also have a systemic effect t...

clinicaltrials.gov Identifier: NCT00094575.

No abstract

Malignant pleural effusions (MPEs) are commonly seen as complications of advanced malignancy, especially in lung cancer and breast cancer. The management will depend on the performance status of the patient, severity of the symptoms, and the primary tumor's response to systemic therapy. Thoracentesis is usually the first step for both diagnostic and therapeutic reasons. Chest tube placement with sclerotherapy is successful in 60 to 90% of cases, but it requires hospitalization for ~1 week. Alternatively, long-term tunneled pleural drainage catheters can be performed on an outpatient basis and are effective in controlling symptoms in 80 to 100% of patients. Additional advantages are the ability to treat trapped lung, large loculated effusions, and bilateral effusions simultaneously, as well as lower charges. Spontaneous pleurodesis can occur in up to 50% of the patients. Tunneled catheters should be considered in all patients with MPE and particularly those who have a reasonable expectancy of being outpatient.