Development, growth, propagation, and angiographic utilization of the rabbit VX2 model of liver cancer: a pictorial primer and “how to” guide

The VX2 tumor is a leporine anaplastic squamous cell carcinoma characterized by rapid growth, hypervascularity, and facile propagation in the skeletal muscle. Since its introduction over 70 years ago, it has been used to model a variety of malignancies, and is commonly employed by interventional radiologists in preclinical investigations of hepatocellular carcinoma. However, despite the widespread and lasting popularity of the model, there are few technical resources detailing its use. Herein, we present a comprehensive pictorial outline of the technical methodology for development, growth, propagation, and angiographic utilization of the rabbit VX2 liver tumor model

Transjugular intrahepatic portosystemic shunt for the treatment of medically refractory ascites

PURPOSEThis study was performed to assess the safety, efficacy, and clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) creation for treatment of medically refractory ascites and to identify prognostic factors for clinical response, morbidity, and mortality. MATERIALS AND METHODSIn this retrospective study, 80 patients (male:female, 52:28; mean age, 56 years; mean Model for End-Stage Liver Disease [MELD] score, 15.1) who underwent elective TIPS creation for refractory ascites between 1999–2012 were studied. A medical record review was performed to identify data on demographics, liver disease, procedures, and outcome. The influence of these parameters on 30-day, 90-day, and one-year mortality was assessed using binary logistic regression. Overall survival was analyzed with Kaplan-Meier statistics. RESULTSTIPS was successfully created using covered (n=70) or bare metal (n=10) stents. Hemodynamic success was achieved in all cases. The mean final portosystemic pressure gradient (PSG) was 6.8 mmHg. Thirty-day complications included mild encephalopathy in 35% of patients. Clinical improvement in ascites occurred in 78% of patients, with complete resolution or a ≥50% decrease in 66% of patients. No predictors of response or optimal PSG threshold were identified. The 30-day, 90-day, and one-year mortality rates were 14%, 23%, and 33%, respectively. Patient age (P = 0.026) was associated with 30-day mortality, while final PSG was associated with 90-day (P = 0.020) and one year (P = 0.032) mortality. No predictors of overall survival were identified. CONCLUSIONTIPS creation effectively treats medically refractory ascites with nearly 80% efficacy. The incidence of mild encephalopathy is nontrivial. Older age and final PSG are associated with mortality, and these factors should be considered in patient selection and procedure performance

Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model

PURPOSEUse of oral sorafenib, an antiangiogenic chemotherapeutic agent for hepatocellular carcinoma (HCC), is limited by an unfavorable side effect profile. Transarterial chemoembolization (TACE) employs targeted intravascular drug administration, and has potential as a novel sorafenib delivery method to increase tumoral concentrations and reduce systemic levels. This study aimed to discern the pharmacokinetics of sorafenib TACE in a rabbit VX2 liver tumor model.METHODSA 3 mg/kg dose of sorafenib ethiodized oil emulsion was delivered via an arterial catheter to VX2 liver tumors in seven New Zealand white rabbits. Following TACE, serum sorafenib levels were measured at days 0, 1, 2, 3, 7, 10, and 14 until the time of sacrifice, after which rabbit livers were harvested for analysis of sorafenib concentrations within treated tumors and normal liver. Liquid chromatography tandem mass spectrometry was used for drug quantification.RESULTSSorafenib uptake within liver tumor and nontumorous liver tissue peaked at mean 3.53 and 0.75 μg/mL, respectively, immediately post-procedure (5:1 tumor to normal tissue drug uptake ratio), before decreasing with a 10–18 hour half-life. Serum sorafenib levels peaked immediately after TACE at a mean value of 58.58 μg/mL before normalizing with a 5.2-hour half-life, suggesting early drug washout from liver into the systemic circulation. Hepatic lab parameters showed transient increase 24 hours post-TACE with subsequent resolution.CONCLUSIONWhile targeted transarterial delivery of sorafenib ethiodized oil emulsion shows preferential tumor uptake compared to normal liver, systemic washout occurs with a short half-life, resulting in high circulating drug levels

Right atrial pressure may impact early survival of patients undergoing transjugular intrahepatic portosystemic shunt creation

Purpose. To elucidate the impact of right atrial (RA) pressure on early mortality after transjugular intrahepatic portosystemic shunt (TIPS).Material and methods. In this single institution retrospective study, 125 patients (M:F = 75:50, mean age 55 years) who underwent TIPS with recorded intra-procedural RA pressures between 1999-2012 were studied. Demographic (age, gender), liver disease (Child-Pugh, Model for End Stage Liver Disease or MELD score), and procedure (indication, urgency, Stent type, portosystemic gradient or PSG reduction, baseline and post-TIPS RA pressure) data were identified, and the influence of these parameters on 30- and 90-day mortality was assessed using binary logistic regression.Results. TIPS were created for variceal hemorrhage (n = 55) and ascites (n = 70). Hemodynamic success rate was 99% (124/125) and mean PSG reduction was 13 mmHg. 30- and 90-day mortality rates were 18% (19/106) and 28% (29/106). Baseline and final RA pressure were significantly associated with 30- (12 vs. 15 mmHg, P = 0.021; 18 vs. 21 mmHg, P = 0.035) and 90-day (12 vs. 14 mmHg, P = 0.022; 18 vs. 20 mmHg, P = 0.024) survival on univariate analysis. Predictive usefulness of RA pressure was not confirmed in multivariate analyses. Area under receiver operator characteristic (AUROC) curve analysis revealed good pre- and post-TIPS RA pressure predictive capacity for 30- (0.779, 0.810) and 90-day (0.813, 0.788) mortality among variceal hemorrhage patients at 14.5 and 21.5 mm Hg thresholds.Conclusion. Intra-procedural RA pressure may have predictive value for early post-TIPS mortality. Pre-procedure consideration and optimization of patient cardiac status may enhance candidate selection, risk stratification, and clinical outcomes, particularly in variceal hemorrhage patients