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

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

Physical Examination and Ultrasound Evaluation of Patients with Superficial Venous Disease

Systematic and standardized evaluation of superficial venous disease, guided by knowledge of the various clinical presentations, venous anatomy, and pathophysiology of reflux, is essential for appropriate diagnosis and optimal treatment. Duplex ultrasonography is the standard for delineating venous anatomy, detecting anatomic variants, and identifying the origin of venous insufficiency. This article reviews tools and techniques essential for physical examination and ultrasound assessment of patients with superficial venous disease

MELD score for prediction of survival after emergent TIPS for acute variceal hemorrhage: derivation and validation in a 101-patient cohort

Background and rationale for the study. The Model for End Stage Liver Disease (MELD) score has not been derived and validated for the emergent transjugular intrahepatic portosystemic shunt (TIPS) population. We sought to identify predictive factors for survival among emergent TIPS patients, and to substantiate MELD for outcomes prognostication in this population.Results. 101 patients with acute life threatening variceal hemorrhage underwent emergent TIPS (defined by failed endoscopic therapy for active bleeding, acute hemoglobin drop, ≥ 2-unit transfusion requirement, and/or vasopressor need) at between 1998-2013. Demographic, clinical, laboratory, and procedure parameters were analyzed for correlation with mortality using Cox proportional hazards regression to derive the prognostic value of MELD constituents. Area under receiver operator characteristic (AUROC) curves was used to assess the capability of MELD prediction of mortality. TIPS were created 119 ± 167 h after initial bleeding events. Hemodynamic success was achieved in 90%. Median final portosystemic pressure gradient was 8 mmHg. Variceal rebleeding incidence was 21%. The four original MELD components showed significant correlation with mortality on multivariate Cox regression: baseline bilirubin (regression coefficient 0.366), creatinine (0.621), international normalized ratio (1.111), and liver disease etiology (0.808), validating the MELD system for emergent cases. No other significant predictive parameters were identified. MELD was an excellent predictor of 90-day mortality in the emergent TIPS population (AUROC = 0.842, 95% CI 0.755-0.928).Conclusions. Based on independent derivation of prognostic constituents and confirmation of predictive accuracy, MELD is a valid and reliable metric for risk stratification and survival projection after emergent TIPS