A 68-year-old male with chronic hepatitis B and C was admitted during April 2009 with hepatocellular carcinoma (HCC). We performed ultrasonography (US)-guided radiofrequency ablation (RFA) using a 2-cm cool-tip electrode (Radionics, Burlington, MA) to treat a 1.5-cm HCC nodule adjacent to the diaphragm in segment VIII (Fig. 1A, arrow). One year later, a 1.0-cm localized tumor progression (Fig. 1B, arrow) identified in the same lesion was again treated using US-guided RFA with a 2-cm cool-tip electrode followed by transcatheter arterial chemoembolization. The patient was hospitalized during December 2010 for right hepatic hydrothorax and ascites, and he was put on a sodium-restricted diet (<85 mEq/day) and treated with spironolactone (50 mg/day) and furosemide (40 mg/day). He was readmitted to the hospital 3 months later with recurrent hepatic hydrothorax. Laboratory findings were: platelets, 63,000/mm3; prothrombin time, 71%; albumin, 2.4 g/dL; bilirubin, 1.9 mg/dL; α-fetoprotein, 9.7 ng/mL; des-γ-carboxy prothrombin, 20 mAU/mL, and a Child-Pugh score of 9. Right hydrothorax and ascites were diagnosed by computed tomography (Fig. 1C). The US contrast agent, perflubutane (Sonazoid; Daiichi-Sankyo, Tokyo, Japan) (0.5 mL) was injected through a 21-gauge needle inserted into the echo-free space of the peritoneal cavity. Perflubutane enhancement was not evident in the pleural cavity immediately after injection (Fig. 1D), but a postural change 15 minutes later elicited jet-like flow from the ascites to a pleural effusion (Fig. 1E and F, jet-like flow: arrow). No adverse events developed during and after the examination. Diaphragmatic damage (Fig. 1G, arrow) that was evident under thoracoscopy was sutured (Fig. 1H). The hepatic hydrothorax did not recur during the 1 year of follow up despite the persistence of ascites.
Hepatic hydrothorax is defined as significant pleural effusion in the absence of primary pulmonary or cardiac disease and in the presence of cirrhosis. The following have been proposed as mechanisms of hepatic hydrothorax: hypoalbuminemia and subsequently decreased colloid osmotic pressure, as well as increased venous pressure in azygos veins leading to plasma leakage into the pleural cavity. Transdiaphragmatic migration of fluid via lymphatic channels and direct ascites leakage develop via diaphragmatic defects1 such as congenital or acquired disorders that are indicated for surgical repair.2
Others have reported that direct leakage can be confirmed using radiolabeled colloids injected intra-abdominally and/or by imaging using radioactive isotopes. Tamano et al. diagnosed direct leakage using an intraperitoneal injection of a US contrast agent.3 Perflubutane is a second-generation imaging agent comprising microbubbles with a median diameter of 2 to 3 μm. It is safely eliminated from the lung soon after injection into a vein or the intraperitoneal cavity. Contrast-enhanced US (CEUS) is less time-consuming and more economical than scintigraphy. The hepatic hydrothorax in the present patient might have resulted from diaphragmatic damage after RFA,4 and CEUS uncovered leakage from ascites into a pleural effusion.
The intraperitoneal injection of perflubutane enables a less-invasive diagnosis of a diaphragmatic defect than either laparoscopy or thoracoscopy, and it can help to localize the site and extent of the diaphragmatic defect to facilitate surgery.