Prophylactic Embolization of the Cystic Artery Before Radioembolization: Feasibility, Safety, and Outcomes

PurposeTo evaluate the safety and efficacy of two different methods of proximal cystic artery embolization in patients undergoing yttrium-90 radioembolization.Materials and methodsForty-six patients had cystic artery embolization performed immediately before yttrium-90 radioembolization, either by using Gelfoam pledgets (n = 35) or coils (n = 11). Clinical symptomatology during the admission and angiographic findings at 1-month follow-up were retrospectively reviewed. Rates of collateralization or recanalization of the cystic artery were compared, as well as the frequency of postprocedural abdominal pain and need for cholecystectomy.ResultsTechnical success was achieved in all patients, and there were no procedural complications related to cystic artery embolization. Of the 11 coil-embolized patients, 5 (45%) demonstrated collateralization of the cystic artery at 1 month, and 1 (9%) demonstrated recanalization of the cystic artery. Of the 35 Gelfoam-embolized cases, 2 (6%) had collateralized at 1 month, and 14 (40%) had recanalized. Two patients (one from each group) had self-limited right upper quadrant pain after the procedure, and one patient in the coil embolization group required cholecystectomy.ConclusionProximal cystic artery embolization is safe and feasible and may be performed during liver-directed embolotherapy to minimize the exposure of the gallbladder to particulate, chemoembolic, or radioembolic agents

3D ToF-SIMS imaging of polymer multilayer films using argon cluster sputter depth profiling

ToF-SIMS imaging with argon cluster sputter depth profiling has provided detailed insight into the three-dimensional (3D) chemical composition of a series of polymer multilayer structures. Depths of more than 15 μm were profiled in these samples while maintaining uniform sputter rates. The 3D chemical images provide information regarding the structure of the multilayer systems that could be used to inform future systems manufacturing and development. This also includes measuring the layer homogeneity, thickness, and interface widths. The systems analyzed were spin-cast multilayers comprising alternating polystyrene (PS) and polyvinylpyrrolidone (PVP) layers. These included samples where the PVP and PS layer thickness values were kept constant throughout and samples where the layer thickness was varied as a function of depth in the multilayer. The depth profile data obtained was observed to be superior to that obtained for the same materials using alternative ion sources such as C60 n+. The data closely reflected the “as manufactured” sample specification, exhibiting good agreement with ellipsometry measurements of layer thickness, while also maintaining secondary ion intensities throughout the profiling regime. The unprecedented quality of the data allowed a detailed analysis of the chemical structure of these systems, revealing some minor imperfections within the polymer layers and demonstrating the enhanced capabilities of the argon cluster depth profiling technique

Radial volumetric imaging breath-hold examination (VIBE) with k-space weighted image contrast (KWIC) for dynamic gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI of the liver: advantages over Cartesian VIBE in the arterial phase

To compare radial volumetric imaging breath-hold examination with k-space weighted image contrast reconstruction (r-VIBE-KWIC) to Cartesian VIBE (c-VIBE) in arterial phase dynamic gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (DCE-MRI) of the liver. We reviewed 53 consecutive DCE-MRI studies performed on a 3-T unit using c-VIBE and 53 consecutive cases performed using r-VIBE-KWIC with full-frame image subset (r-VIBEfull) and sub-frame image subsets (r-VIBEsub; temporal resolution, 2.5-3 s). All arterial phase images were scored by two readers on: (1) contrast-enhancement ratio (CER) in the abdominal aorta; (2) scan timing; (3) artefacts; (4) visualisation of the common, right, and left hepatic arteries. Mean abdominal aortic CERs for c-VIBE, r-VIBEfull, and r-VIBEsub were 3.2, 4.3 and 6.5, respectively. There were significant differences between each group (P < 0.0001). The mean score for c-VIBE was significantly lower than that for r-VIBEfull and r-VIBEsub in all factors except for visualisation of the common hepatic artery (P < 0.05). The mean score of all factors except for scan timing for r-VIBEsub was not significantly different from that for r-VIBEfull. Radial VIBE-KWIC provides higher image quality than c-VIBE, and r-VIBEsub features high temporal resolution without image degradation in arterial phase DCE-MRI. aEuro cent Radial VIBE-KWIC minimised artefact and produced high-quality and high-temporal-resolution images. aEuro cent Maximum abdominal aortic enhancement was observed on sub-frame images of r-VIBE-KWIC. aEuro cent Using r-VIBE-KWIC, optimal arterial phase images were obtained in over 90 %. aEuro cent Using r-VIBE-KWIC, visualisation of the hepatic arteries was improved. aEuro cent A two-reader study revealed r-VIBE-KWIC's advantages over Cartesian VIBE.ArticleEUROPEAN RADIOLOGY. 24(6):1290-1299 (2014)journal articl

Liver-Specific Commd1 Knockout Mice Are Susceptible to Hepatic Copper Accumulation

Canine copper toxicosis is an autosomal recessive disorder characterized by hepatic copper accumulation resulting in liver fibrosis and eventually cirrhosis. We have identified COMMD1 as the gene underlying copper toxicosis in Bedlington terriers. Although recent studies suggest that COMMD1 regulates hepatic copper export via an interaction with the Wilson disease protein ATP7B, its importance in hepatic copper homeostasis is ill-defined. In this study, we aimed to assess the effect of Commd1 deficiency on hepatic copper metabolism in mice. Liver-specific Commd1 knockout mice (Commd1Δhep) were generated and fed either a standard or a copper-enriched diet. Copper homeostasis and liver function were determined in Commd1Δhep mice by biochemical and histological analyses, and compared to wild-type littermates. Commd1Δhep mice were viable and did not develop an overt phenotype. At six weeks, the liver copper contents was increased up to a 3-fold upon Commd1 deficiency, but declined with age to concentrations similar to those seen in controls. Interestingly, Commd1Δhep mice fed a copper-enriched diet progressively accumulated copper in the liver up to a 20-fold increase compared to controls. These copper levels did not result in significant induction of the copper-responsive genes metallothionein I and II, neither was there evidence of biochemical liver injury nor overt liver pathology. The biosynthesis of ceruloplasmin was clearly augmented with age in Commd1Δhep mice. Although COMMD1 expression is associated with changes in ATP7B protein stability, no clear correlation between Atp7b levels and copper accumulation in Commd1Δhep mice could be detected. Despite the absence of hepatocellular toxicity in Commd1Δhep mice, the changes in liver copper displayed several parallels with copper toxicosis in Bedlington terriers. Thus, these results provide the first genetic evidence for COMMD1 to play an essential role in hepatic copper homeostasis and present a valuable mouse model for further understanding of the molecular mechanisms underlying hepatic copper homeostasis

COMMD1-Mediated Ubiquitination Regulates CFTR Trafficking

The CFTR (cystic fibrosis transmembrane conductance regulator) protein is a large polytopic protein whose biogenesis is inefficient. To better understand the regulation of CFTR processing and trafficking, we conducted a genetic screen that identified COMMD1 as a new CFTR partner. COMMD1 is a protein associated with multiple cellular pathways, including the regulation of hepatic copper excretion, sodium uptake through interaction with ENaC (epithelial sodium channel) and NF-kappaB signaling. In this study, we show that COMMD1 interacts with CFTR in cells expressing both proteins endogenously. This interaction promotes CFTR cell surface expression as assessed by biotinylation experiments in heterologously expressing cells through regulation of CFTR ubiquitination. In summary, our data demonstrate that CFTR is protected from ubiquitination by COMMD1, which sustains CFTR expression at the plasma membrane. Thus, increasing COMMD1 expression may provide an approach to simultaneously inhibit ENaC absorption and enhance CFTR trafficking, two major issues in cystic fibrosis

Canine models of copper toxicosis for understanding mammalian copper metabolism

Hereditary forms of copper toxicosis exist in man and dogs. In man, Wilson’s disease is the best studied disorder of copper overload, resulting from mutations in the gene coding for the copper transporter ATP7B. Forms of copper toxicosis for which no causal gene is known yet are recognized as well, often in young children. Although advances have been made in unraveling the genetic background of disorders of copper metabolism in man, many questions regarding disease mechanisms and copper homeostasis remain unanswered. Genetic studies in the Bedlington terrier, a dog breed affected with copper toxicosis, identified COMMD1, a gene that was previously unknown to be involved in copper metabolism. Besides the Bedlington terrier, a number of other dog breeds suffer from hereditary copper toxicosis and show similar phenotypes to humans with copper storage disorders. Unlike the heterogeneity of most human populations, the genetic structure within a purebred dog population is homogeneous, which is advantageous for unraveling the molecular genetics of complex diseases. This article reviews the work that has been done on the Bedlington terrier, summarizes what was learned from studies into COMMD1 function, describes hereditary copper toxicosis phenotypes in other dog breeds, and discusses the opportunities for genome-wide association studies on copper toxicosis in the dog to contribute to the understanding of mammalian copper metabolism and copper metabolism disorders in man