Nonresectable Hepatocellular Carcinoma: Long-term Toxicity in Patients Treated with Transarterial Chemoembolization - Single-Center Experience

Purpose: To determine the toxicity profile of transarterial chemoembolization (TACE) at 6 months and 1 year after treatment in patients with hepatocellular carcinoma (HCC) in a standardized oncology protocol so that TACE could be compared with systemic chemotherapeutic regimens for liver cancer. Materials and Methods: The study was authorized by the institutional review board. Between January 2002 and January 2007, 190 patients (155 men, 35 women; median age, 65 years; age range, 18 – 84 years) with HCC who underwent TACE treatment were identified from a prospectively collected database. Clinical records of complete blood cell counts and chemical profiles at baseline and at 6 and 12 months after treatment were studied retrospectively. Toxicity was graded according to the common terminology criteria for adverse events (CTCAE). A transition (survival) analysis perspective was used to estimate the distribution of toxicity grades. Patient survival from the first TACE session was calculated with Kaplan-Meier analysis. Results: Grade 3 or 4 toxicity 6 and 12 months, respectively, after treatment included leukocytopenia (7% and 19%); anemia (9% and 19%); thromobocytopenia (13% and 23%); prolonged activated partial thromboplastin time (8% and 18%); elevated aspartate aminotransferase (15% and 18%), alanine aminotransferase (10% and 18%), and alkaline phosphatase (8% and 18%) levels; hypoalbuminemia (10% and 19%); hyperbilirubinemia (10% and 22%); and alopecia (18%). The cumulative survival rate was 58% at 1 year, 39% at 2 years, and 29% at 3 years. These toxicity rates were considerably lower than those reported after treatment with currently used systemic chemotherapeutic agents. Conclusion: Study results show that TACE has a favorable long-term toxicity profile in patients with HCC. Data clearly support the role of TACE in the treatment of patients with nonresectable HHC

Celiac Artery Stenting to Facilitate Hepatic Yttrium-90 Radioembolization Therapy

Radioembolization offers a novel way to treat the nonresectable, liver predominant hepatic malignancies with better tumor response and overall progression-free survival rates. Transarterial catheter-based radioembolization procedure involves the hepatic arterial administration of glass- or resin-based beta emitting Yttirum-90 microspheres. Safe delivery of the tumoricidal radiation dose requires careful angiogram planning and coil embolization to quantify lung shunting and prevent systemic toxicity, respectively. Diagnostic pretreatment angiogram also serves to identify the hepatic arterial variant anatomy and other coexisting pathologies that might require a different or alternative approach. We describe a complex case of celiac artery stenosis with tortuous pancreaticoduodenal arterial arcade precluding access to the right hepatic artery for performing radioembolization. Celiac artery stenting of the stenosis was performed to facilitate subsequent safe and successful Yttrium-90 microsphere radioembolization

Human Adipose-Derived Stromal Cells Delivered on Decellularized Muscle Improve Muscle Regeneration and Regulate RAGE and P38 MAPK

Volumetric muscle loss (VML) is the acute loss of muscle mass due to trauma. Such injuries occur primarily in the extremities and are debilitating, as there is no clinical treatment to restore muscle function. Pro-inflammatory advanced glycation end-products (AGEs) and the soluble receptor for advanced glycation end-products (RAGE) are known to increase in acute trauma patient’s serum and are correlated with increased injury severity. However, it is unclear whether AGEs and RAGE increase in muscle post-trauma. To test this, we used decellularized muscle matrix (DMM), a pro-myogenic, non-immunogenic extracellular matrix biomaterial derived from skeletal muscle. We delivered adipose-derived stromal cells (ASCs) and primary myoblasts to support myogenesis and immunomodulation (N = 8 rats/group). DMM non-seeded and seeded grafts were compared to empty defect and sham controls. Then, 56 days after surgery muscle force was assessed, histology characterized, and protein levels for AGEs, RAGE, p38 MAPK, and myosin heavy chains were measured. Overall, our data showed improved muscle regeneration in ASC-treated injury sites and a regulation of RAGE and p38 MAPK signaling, while myoblast-treated injuries resulted in minor improvements. Taken together, these results suggested that ASCs combined with DMM provides a pro-myogenic microenvironment with immunomodulatory capabilities and indicates further exploration of RAGE signaling in VML