Transarterial RAdioembolization versus ChemoEmbolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Hepatocellular carcinoma is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10 to 15% of hepatocellular carcinoma patients are suitable candidates for treatment with curative intent, such as hepatic resection and liver transplantation. A majority of patients have locally advanced, liver restricted disease (Barcelona Clinic Liver Cancer (BCLC) staging system intermediate stage). Transarterial loco regional treatment modalities offer palliative treatment options for these patients; transarterial chemoembolization (TACE) is the current standard treatment. During TACE, a catheter is advanced into the branches of the hepatic artery supplying the tumor, and a combination of embolic material and chemotherapeutics is delivered through the catheter directly into the tumor. Yttrium-90 radioembolization (90Y-RE) involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a beta-emitting isotope, delivering selective internal radiation to the tumor. 90Y-RE is increasingly used in clinical practice for treatment of intermediate stage hepatocellular carcinoma, but its efficacy has never been prospectively compared to that of the standard treatment (TACE). In this study, we describe the protocol of a multicenter randomized controlled trial aimed at comparing the effectiveness of TACE and 90Y-RE for treatment of patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma.Methods/designIn this pragmatic randomized controlled trial, 140 patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma, with Eastern Cooperative Oncology Group performance status 0 to 1 and Child-Pugh A to B will be randomly assigned to either 90Y-RE or TACE with drug eluting beads. Patients assigned to 90Y-RE will first receive a diagnostic angiography, followed by the actual transarterial treatment, which can be divided into two sessions in case of bilobar disease. Patients assigned to TACE will receive a maximum of three consecutive transarterial treatment sessions. Patients will undergo structural follow-up for a timeframe of two years post treatment. Post procedural magnetic resonance imaging (MRI) will be performed at one and three months post trial entry and at three-monthly intervals thereafter for two years to assess tumor response. Primary outcome will be time to progression. Secondary outcomes will be overall survival, tumor response according to the modified RECIST criteria, toxicities/adverse events, treatment related effect on total liver function, quality of life, treatment-related costs and cost-effectiveness.Trial registrationNCT01381211.     

High levels of linkage disequilibrium and associations with forage quality at a Phenylalanine Ammonia-Lyase locus in European maize (Zea mays L.) inbreds

Forage quality of maize is influenced by both the content and structure of lignin in the cell wall. Phenylalanine Ammonia-Lyase (PAL) catalyzes the first step in lignin biosynthesis in plants; the deamination of L-phenylalanine to cinnamic acid. Successive enzymatic steps lead to the formation of three monolignols, constituting the complex structure of lignin. We have cloned and sequenced a PAL genomic sequence from 32 maize inbred lines currently employed in forage maize breeding programs in Europe. Low nucleotide diversity and excessive linkage disequilibrium (LD) was identified at this PAL locus, possibly reflecting selective constrains resulting from PAL being the first enzyme in the monolignol, and other, pathways. While the association analysis was affected by extended LD and population structure, several individual polymorphisms were associated with neutral detergent fiber (not considering population structure) and a single polymorphism was associated with in vitro digestibility of organic matter (considering population structure).     

Oxygen and carbon dioxide fluctuations in burrows of subterranean blind mole rats indicate tolerance to hypoxic-hypercapnic stresses

The composition of oxygen (O2), carbon dioxide (CO2), and soil humidity in the underground burrows from three species of the Israeli subterranean mole rat Spalax ehrenbergi superspecies were studied in their natural habitat. Two geographically close populations of each species from contrasting soil types were probed. Maximal CO2 levels (6.1%) and minimal O2 levels (7.2%) were recorded in northern Israel in the breeding mounds of S. carmeli in a flooded, poor drained field of heavy clay soil with very high volumetric water content. The patterns of gas fluctuations during the measurement period among the different Spalax species studied were similar. The more significant differentiation in gas levels was not among species, but between neighboring populations inhabiting heavy soils or light soils: O2 was lower and CO2 was higher in the heavy soils (clay and basaltic) compared to the relatively light soils (terra rossa and rendzina). The extreme values of gas concentration, which occurred during the rainy season, seemed to fluctuate with partial flooding of the tunnels, animal digging activity, and over-crowded breeding mounds inhabited by a nursing female and her offspring. The gas composition and soil water content in neighboring sites with different soil types indicated large differences in the levels of hypoxic-hypercapnic stress in different populations of the same species. A growing number of genes associated with hypoxic stress have been shown to exhibit structural and functional differences between the subterranean Spalax and the above-ground rat (Rattus norvegicus), probably reflecting the molecular adaptations that Spalax went through during 40 million years of evolution to survive efficiently in the severe fluctuations in gas composition in the underground habitat.     

Polymorphisms in monolignol biosynthetic genes are associated with biomass yield and agronomic traits in European maize (<Emphasis Type="Italic">Zea mays</Emphasis> L.)

Background  

Reduced lignin content leads to higher cell wall digestibility and, therefore, better forage quality and increased conversion of lignocellulosic biomass into ethanol. However, reduced lignin content might lead to weaker stalks, lodging, and reduced biomass yield. Genes encoding enzymes involved in cell wall lignification have been shown to influence both cell wall digestibility and yield traits.