Chemoembolization Beyond Hepatocellular Carcinoma: What Tumors Can We Treat and When?

Liver metastases are the most common malignancy found in the liver and are 20 to 40 times more common than primary hepatic tumors, including hepatocellular carcinoma. Patients with liver metastases often present with advanced disease and are not eligible for curative-intent surgery or ablative techniques. The unique hepatic arterial blood supply of liver metastases allows interventional radiologists to target these tumors with transarterial therapies. Transarterial chemoembolization (TACE) has been studied in the treatment of liver metastases originating from a variety of primary malignancies and has demonstrated benefits in terms of hepatic progression-free survival, overall survival, and symptomatic relief, among other benefits. Depending on the primary tumor from which they originate, liver metastases may have different indications for TACE, may utilize different TACE regimens and techniques, and may result in different post-procedural outcomes. This review offers an overview of TACE techniques and specific considerations in the treatment of liver metastases, provides an in-depth review of TACE in the treatment of liver metastases originating from colorectal cancer, neuroendocrine tumor, and uveal melanoma, which represent some of the many tumors beyond hepatocellular carcinoma that can be treated by TACE, and summarizes data regarding when one should consider TACE in their treatment algorithms.

Venous Stents: Current Status and Future Directions.

Venous outflow obstruction is a dominant contributor to chronic venous disease. Treatment of venous disease has historically been limited by available vascular stent technology not specifically designed for the venous system. The ideal venous stent must provide requisite flexibility, strength, and accurate deployment for the anatomical and pathophysiological conditions of chronic venous disease. Venous stent technology is advancing with multiple dedicated venous stents currently available in Europe and with investigational device exemption studies ongoing in the United States. These technological advancements are promising for patients suffering from chronic venous disease. This article discusses the current status and future directions of venous stents.

Rapid and profound potentiation of Apo2L/TRAIL-mediated cytotoxicity and apoptosis in thoracic cancer cells by the histone deacetylase inhibitor Trichostatin A: the essential role of the mitochondria-mediated caspase activation cascade.

Apo2L/TRAIL is actively investigated as a novel targeted agent to directly induce apoptosis of susceptible cancer cells. Apo2L/TRAIL-refractory cells can be sensitized to the cytotoxic effect of this ligand by cytotoxic chemotherapeutics. The aim of this study was to evaluate the in vitro tumoricidal activity of the Apo2L/TRAIL + Trichostatin A in cultured thoracic cancer cells and to elucidate the molecular basis of the synergistic cytotoxicity of this combination. Concurrent exposure of cultured cancer cells to sublethal concentrations of Apo2L/TRAIL and Trichostatin A resulted in profound enhancement of Apo2L/TRAIL-mediated cytotoxicity in all cell lines regardless of their intrinsic susceptibility to this ligand. This combination was not toxic to primary normal cells. While Apo2L/TRAIL alone or Trichostatin A alone mediated < 20% cell death, 60 to 90% of cancer cells were apoptotic following treatment with TSA + Apo2L/TRAIL combinations. Complete translocation of Bax from the cytosol to the mitochondria compartment was mainly observed in combination-treated cells and this was correlated with robust elevation of caspase 9 proteolytic activity indicative of activation of the mitochondria apoptogenic effect. Profound TSA + Apo2L/TRAIL-mediated cytotoxicity and apoptosis were completely abrogated by either Bcl2 over-expression or by the selective caspase 9 inhibitor, highlighting the essential role of mitochondria-dependent apoptosis signaling cascade in this process. Moreover, increased caspase 8 activity observed in cells treated with the TSA + Apo2L/TRAIL combination was completely suppressed by Bcl-2 over-expression or by the selective caspase 9 inhibitor indicating that the elevated caspase 8 activity in combination-treated cells was secondary to a mitochondria-mediated amplification feedback loop of caspase activation. These finding form the basis for further development of HDAC inhibitors + Apo2L/TRAIL combination as novel targeted therapy for thoracic malignancies.