Brain artery diameters and risk of dementia and stroke.

INTRODUCTION: We tested the association of brain artery diameters with dementia and stroke risk in three distinct population-based studies using conventional T2-weighted brain magnetic resonance imaging (MRI) images. METHODS: We included 8420 adults > 40 years old from three longitudinal population-based studies with brain MRI scans. We estimated and meta-analyzed the hazard ratios (HRs) of the brain and carotids and basilar diameters associated with dementia and stroke. RESULT: Overall and carotid artery diameters > 95th percentile increased the risk for dementia by 1.74 (95% confidence interval [CI], 1.13-2.68) and 1.48 (95% CI, 1.12-1.96) fold, respectively. For stroke, meta-analyses yielded HRs of 1.59 (95% CI, 1.04-2.42) for overall arteries and 2.11 (95% CI, 1.45-3.08) for basilar artery diameters > 95th percentile. DISCUSSION: Individuals with dilated brain arteries are at higher risk for dementia and stroke, across distinct populations. Our findings underline the potential value of T2-weighted brain MRI-based brain diameter assessment in estimating the risk of dementia and stroke.

Novel characterization of the relationship between verbal list-learning outcomes and hippocampal subfields in healthy adults.

The relationship between hippocampal subfield volumetry and verbal list-learning test outcomes have mostly been studied in clinical and elderly populations, and remain controversial. For the first time, we characterized a relationship between verbal list-learning test outcomes and hippocampal subfield volumetry on two large separate datasets of 447 and 1,442 healthy young and middle-aged adults, and explored the processes that could explain this relationship. We observed a replicable positive linear correlation between verbal list-learning test free recall scores and CA1 volume, specific to verbal list learning as demonstrated by the hippocampal subfield volumetry independence from verbal intelligence. Learning meaningless items was also positively correlated with CA1 volume, pointing to the role of the test design rather than word meaning. Accordingly, we found that association-based mnemonics mediated the relationship between verbal list-learning test outcomes and CA1 volume. This mediation suggests that integrating items into associative representations during verbal list-learning tests explains CA1 volume variations: this new explanation is consistent with the associative functions of the human CA1.

The Perception of Plastic Surgery by Community-Based, Private Practice Nurses: A French National Descriptive Study.

Plastic surgery is a dynamic field but remains poorly understood by general practitioners, medical students, health professionals, and the public. The main health care professionals in the community who are involved in the follow-up of plastic surgery patients are nurses; they help to facilitate wound healing and rehabilitation in the postoperative period. In this study, the authors assessed the medical knowledge and perceptions of plastic surgery by nurses working in the community setting and explored their understanding of classical scenarios commonly encountered in reconstructive surgery. An online survey was designed to assess the demographics of nurses working in the community in France and their knowledge of plastic surgery. This was disseminated to all practicing nurses working outside of hospitals by means of an online social network from the period of April 2019 to June 2019. The survey was completed by 318 nurses. Specific training in plastic surgical nursing will be required to optimize the management of these patients following discharge from hospital. This gap in knowledge may affect patient recovery negatively.

Midterm Recanalization after Arterial Embolization Using Hydrogel-Coated Coils versus Fibered Coils in an Animal Model.

PURPOSE: To compare angiographic and pathologic effects (ie, occlusion, recanalization) after embolization with Hydrogel-coated coils (HydroCoils) and fibered coils in the renal and internal iliac arteries after 7 days and 1 and 4 months in an animal model. MATERIALS AND METHODS: Twelve sheep had 1 internal iliac and 1 renal artery randomly embolized with HydroCoils or fibered coils. Renal and internal iliac arteries were embolized with detachable 0.018-inch coils and pushable 0.035-inch coils, respectively. All animals had control angiography performed at 7 days, and 1 and 4 months to assess recanalization before euthanasia. Recanalization and inflammation were evaluated via pathologic examination. RESULTS: At 1 month, 100% of arteries embolized with HydroCoils were occluded vs 50% of those embolized with fibered coils (P = .004). At 4 months, 80% of arteries embolized with HydroCoils were occluded vs 25% of those embolized with fibered coils (P = .01). Surface of vessel occlusion was significantly greater for iliac arteries (96.7% ± 8.9) than for renal arteries (94.2% ± 5.3; P = .0076). Surface of occlusion of the renal arteries (92.2% ± 5.1) was lower for fibered coils than for HydroCoils (96.8% ± 4.7; P = .0287). Surface percentage of thrombus was significantly lower for HydroCoils than for fibered coils (P < .0001). Surface percentage of thrombus was correlated with surface percentage of recanalization (P = .0181). CONCLUSIONS: After 4 months, 75% of arteries embolized with fibered coils were recanalized vs 20% of those embolized with HydroCoils (P = .01). Reduced amount of thrombus after embolization with HydroCoils accounted for a reduced rate of arterial recanalization.

Lymphatic Transport and Lymph Node Location of Microspheres Subcutaneously Injected in the Vicinity of Tumors in a Rabbit Model of Breast Cancer.

PURPOSE: To assess the lymphatic transport of microparticles of 100 nm, 1 µm and 10 µm subcutaneously injected into the breast area of healthy and tumor-bearing rabbits, and to analyze their location in lymph node (LN) in relation to malignant cells. METHODS: Female rabbits (n = 9) bearing a VX2 tumor in one thoracic mammary gland were subcutaneously injected at D15 with polystyrene fluorescent particles around the nipple, on the tumor and on the healthy sides. The tumor and the LN measured by ultrasound at D9, D15 and D20 were explanted at D20. The LN metastases were evaluated by cytokeratin staining. LN uptake of the particles was measured by quantifying the green fluorescence surface in hot spot regions of healthy and pathologic LN. RESULTS: All animals developed mammary tumors. Metastases were found in 39% of LN from the tumor side. LN invasion was significantly lower for the 10 µm group versus the 100 nm group (p < 0.0348). The fully invaded area of metastatic LN contained significantly less 100 nm and 1 µm particles compared to the low and non-invaded regions and to the healthy LN. In the invaded LN, the 1 µm MS occupied more surface than the 100 nm particles. CONCLUSIONS: 1 µm MS arrived numerously into the areas low-invaded and non-invaded by the tumoral cells of the pathologic LN, but they were very rare in the fully invaded regions. Compared to the 100 nm nanospheres, the 1 µm were better retained (20 times) into the sentinel LN, showing the advantage of micrometric particles for lymph-targeted chemotherapy when injected before complete invasion by metastases.

Predicting hemispheric dominance for language production in healthy individuals using support vector machine.

We used a Support Vector Machine (SVM) classifier to assess hemispheric pattern of language dominance of 47 individuals categorized as non-typical for language from their hemispheric functional laterality index (HFLI) measured on a sentence minus word-list production fMRI-BOLD contrast map. The SVM classifier was trained at discriminating between Dominant and Non-Dominant hemispheric language production activation pattern on a group of 250 participants previously identified as Typicals (HFLI strongly leftward). Then, SVM was applied to each hemispheric language activation pattern of 47 non-typical individuals. The results showed that at least one hemisphere (left or right) was found to be Dominant in every, except 3 individuals, indicating that the "dominant" type of functional organization is the most frequent in non-typicals. Specifically, left hemisphere dominance was predicted in all non-typical right-handers (RH) and in 57.4% of non-typical left-handers (LH). When both hemisphere classifications were jointly considered, four types of brain patterns were observed. The most often predicted pattern (51%) was left-dominant (Dominant left-hemisphere and Non-Dominant right-hemisphere), followed by right-dominant (23%, Dominant right-hemisphere and Non-Dominant left-hemisphere) and co-dominant (19%, 2 Dominant hemispheres) patterns. Co-non-dominant was rare (6%, 2 Non-Dominant hemispheres), but was normal variants of hemispheric specialization. In RH, only left-dominant (72%) and co-dominant patterns were detected, while for LH, all types were found, although with different occurrences. Among the 10 LH with a strong rightward HFLI, 8 had a right-dominant brain pattern. Whole-brain analysis of the right-dominant pattern group confirmed that it exhibited a functional organization strictly mirroring that of left-dominant pattern group. Hum Brain Mapp 38:5871-5889, 2017. © 2017 Wiley Periodicals, Inc.

Laparoscopic subperitoneal injection of chemo-loaded particles lowers tumor growth on a rabbit model of peritoneal carcinomatosis.

The purpose of our study was to assess the effect of controlled-release chemotherapy on the growth and viability of peritoneal carcinomatosis treated by subperitoneal injection in a rabbit VX2 model. A model of peritoneal carcinomatosis was created by laparoscopic injection of VX2 tumor in the left and right broad ligaments of 12 White New Zealand rabbits. At day 12, each tumor was randomly treated with a peritumoral injection of 0.5 mL microspheres loaded with doxorubicin (DEM-DOX) or unloaded (DEM-BLAND). Seven days after treatment, tumor volume, tumor viability in histology, local tumor necrosis in contact with DEM, and doxorubicin concentration profile around the drug eluting microspheres (DEM) were measured. Tumor volume was significantly lower in the DEM-DOX group (3.6 ± 3.2 cm3) compared with the DEM-BLAND group (8.9 ± 5.4 cm3) (p = 0.0425). The percentage of viable tumor tissue was significantly lower in the DEM-DOX group (38% ± 17%) compared with the DEM-BLAND group (56% ± 20%) (p = 0.0202). Tissue necrosis was observed around all DEM-DOX up to a distance of 1.094 ± 0.852 mm and never observed around DEM-BLAND. Drug concentration was above the therapeutic level of 1.0 µM up to a distance of 1.4 mm from the DEM to the tumor. Laparoscopic subperitoneal injection of chemo-loaded particles is feasible and lowers tumor growth and viability in a rabbit model of peritoneal carcinomatosis after 1 week.

Automated Quantification of Tumor Viability in a Rabbit Liver Tumor Model after Chemoembolization Using Infrared Imaging.

The rabbit VX2 tumor is a fast-growing carcinoma model commonly used to study new therapeutic devices, such as catheter-based therapies for patients with inoperable hepatocellular carcinoma. The evaluation of tumor viability after such locoregional therapies is essential to directing hepatocellular carcinoma management. We used infrared microspectroscopy for the automatic characterization and quantification of the VX2 liver tumor viability after drug-eluting beads transarterial chemoembolization (DEB-TACE). The protocol consisted of K-means clustering followed by principal component analysis (PCA) and linear discriminant analysis (LDA). The K-means clustering was used to classify the spectra from the infrared images of control or treated tumors and to build a database of many tissue spectra. On the basis of this reference library, the PCA-LDA analysis was used to build a predictive model to identify and quantify automatically tumor viability on unknown tissue sections. For the DEB group, the LDA model determined that the surface of tumor necrosis represented 91.6% ± 8.9% (control group: 33.1% ± 19.6%; Mann-Whitney P = 0.0004) and the viable tumor 2.6% ± 4% (control group: 62.2% ± 15.2%; Mann-Whitney P = 0.0004). Tissue quantification measurements correlated well with tumor necrosis (r = 0.827, P < 0.0001) and viable tumor (r = 0.840, P < 0.0001). Infrared imaging and PCA-LDA analysis could be helpful for easily assessing tumor viability.

Safety and efficacy compared between irinotecan-loaded microspheres HepaSphere and DC bead in a model of VX2 liver metastases in the rabbit.

PURPOSE: To compare irinotecan-eluting HepaSphere (BioSphere Medical, Roissy-en-France, France) and DC Bead (Biocompatibles UK Ltd, London, United Kingdom) embolization microspheres for distribution in tumors, release properties, tolerance, and antitumor effects in a model of liver metastases in the rabbit. MATERIALS AND METHODS: Multiple liver tumors were created by injection of a VX2 cell suspension in the portal vein of rabbits. After 2 weeks, embolization of the proper hepatic artery was performed with a fixed volume of bland HepaSphere (n = 5), irinotecan-loaded HepaSphere (n = 6), or irinotecan-loaded DC Bead (n = 5) microspheres. Untreated animals injected with VX2 cells served as control animals (n = 5). Plasma pharmacokinetics of irinotecan and its metabolite SN38 were assessed. Histopathology and gene expression analysis were performed 3 days after treatment. RESULTS: Among all treated groups, there was no significant difference in liver enzymes or liver damage on histology. Irinotecan-loaded HepaSphere microspheres showed a faster release of drug than DC Bead microspheres leading to a twofold higher concentration of drug in plasma for HepaSphere microspheres. HepaSphere microspheres were less frequently found inside tumor nodules on histology than DC Bead microspheres (11% vs 48%, P < .001) because of their larger size. Tumor necrosis was significantly greater for rabbits given irinotecan-loaded HepaSphere microspheres (69% of total tumor surface) and rabbits given DC Bead microspheres (50% of total tumor surface) compared with control animals (24% of total tumor surface, P = .006 and P = .047). CONCLUSIONS: HepaSphere and DC Bead microspheres loaded with irinotecan caused significant necrosis of tumor nodules in a model of VX2 liver metastases. This outcome was mostly due to irinotecan delivery rather than vascular occlusion by the microspheres and was greater for HepaSphere microspheres compared with DC Bead microspheres.

Validation of death prediction after breast cancer relapses using joint models.

BACKGROUND: Cancer relapses may be useful to predict the risk of death. To take into account relapse information, the Landmark approach is popular. As an alternative, we propose the joint frailty model for a recurrent event and a terminal event to derive dynamic predictions of the risk of death. METHODS: The proposed prediction settings can account for relapse history or not. In this work, predictions developed on a French hospital series of patients with breast cancer are externally validated on UK and Netherlands registry data. The performances in terms of prediction error and calibration are compared to those from a Landmark Cox model. RESULTS: The error of prediction was reduced when relapse information was taken into account. The prediction was well-calibrated, although it was developed and validated on very different populations. Joint modelling and Landmark approaches had similar performances. CONCLUSIONS: When predicting the risk of death, accounting for relapses led to better prediction performance. Joint modelling appeared to be suitable for such prediction. Performance was similar to the landmark Cox model, while directly quantifying the correlation between relapses and death.

In vitro evaluation of S-(+)-ibuprofen as drug candidate for intra-articular drug delivery system.

Intra-articular drug delivery systems (DDSs) are envisaged as interesting alternative to locally release non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen to reduce pain in patients with osteoarthritis. The present study examines the efficacy of S-(+)-ibuprofen on cartilage degradation as drug candidate for DDS loading. Humeral cartilage and joint capsule explants were collected from healthy sheep shoulder joints and they were cultured in mono- or in co-culture for 13 days with LPS in combination with S-(+)-ibuprofen at 50 µM and 1 mM. S-(+)-ibuprofen (50 µM) blocked prostaglandins production in LPS-activated explants but did not reduce cartilage degradation. By contrast, 1 mM S-(+)-ibuprofen treatment of cartilage explants reduced nitric oxide synthesis by 51% (p = 0.0072), proteoglycans degradation by 35% (p = 0.0114) and expression of serum amyloid protein - the main protein induced upon LPS challenge - by 44% (p < 0.0001). On contrary, in presence of synovial membrane, the protective effects of S-(+)-ibuprofen on cartilage damages were significantly diminished. At 1mM, S-(+)-ibuprofen reduced the cell lysis during culture of cartilage and joint capsule either in mono- or in co-culture. This study performed on sheep explants shows that 1 mM S-(+)-ibuprofen inhibited cartilage degradation via a mechanism independent of cyclooxygenase inhibition. Reduction of prostaglandins synthesis at 50 µM in all treatment groups and reduction of cartilage degradation observed at 1 mM suggest that S-(+)-ibuprofen could be considered as a promising drug candidate for the loading of intra-articular DDS.

A novel resorbable embolization microsphere for transient uterine artery occlusion: a comparative study with trisacryl-gelatin microspheres in the sheep model.

PURPOSE: To evaluate angiographic recanalization, inflammatory reaction, and uterine damage after sheep uterine artery embolization (UAE) with a novel calibrated resorbable embolization microsphere (REM) and compare the results with control nonresorbable microspheres. MATERIALS AND METHODS: Six hormonally artificially cycled sheep underwent bilateral UAE until stasis with either REM or trisacryl-gelatin microspheres (TGMS). At 7 days, control angiograms were obtained to assess the residual vascularization at arterial and parenchymal phases. The animals were then sacrificed for analysis of the presence of microspheres, inflammatory foreign body reaction, and surface areas of uterine damage. RESULTS: Mean volume of microspheres injected per uterine artery (UA) or per animal did not differ between groups. At day 7, the flow was normal for six of six UAs that received embolization with REM versus only three of six UAs with TGMS (P = .0455, χ(2) test). Uterine parenchymography showed no defects in six UAs in the REM group versus five defects in six UAs in the TGMS group (P = .0060, χ(2) test). No REM or residual fragments of microspheres were observed on histologic analysis. TGMS were observed in tissues and accompanied by a mild inflammatory response. Necrosis rates were not significantly different between the two products, either in endometrium (REM 23.5% ± 28.8% [median 8.1%] vs TGMS 21.8% ± 23.7% [median 14.6%]) or in myometrium (REM 8.2% ± 22.7% [median 0.0%] vs TGMS 8.8% ± 20.8% [median 0.9%]). Endometrium alteration rate was lower with REM than with TGMS (39.7% ± 25.7% [median 34%] vs 60.6% ± 27.1% [median 71%]; P = .0060, Mann-Whitney test). Myometrium alteration rates were not significantly different between REM (45.7% ± 37.1% [median 63.0%]) and TGMS (37.8% ± 34.0% [median 19.1%]). CONCLUSIONS: At 1 week after sheep UAE with REM, the recanalization was complete, the microspheres were completely degraded, and there was no remnant inflammatory response.

Dynamic prediction of risk of death using history of cancer recurrences in joint frailty models.

Evaluating the prognosis of patients according to their demographic, biological, or disease characteristics is a major issue, as it may be used for guiding treatment decisions. In cancer studies, typically, more than one endpoint can be observed before death. Patients may undergo several types of events, such as local recurrences and distant metastases, with death as the terminal event. Accuracy of clinical decisions may be improved when the history of these different events is considered. Thus, it may be useful to dynamically predict patients' risk of death using recurrence history. As previously applied within the framework of joint models for longitudinal and time to event data, we propose a dynamic prediction tool based on joint frailty models. Joint modeling accounts for the dependence between recurrent events and death, by the introduction of a random effect shared by the two processes. We estimate the probability of death between the prediction time t and a horizon t + w, conditional on information available at time t. Prediction can be updated with the occurrence of a new event. We proposed and compared three prediction settings, taking into account three different information levels. The proposed tools are applied to patients diagnosed with a primary invasive breast cancer and treated with breast-conserving surgery, followed for more than 10 years in a French comprehensive cancer center.

Targeting and recanalization after embolization with calibrated resorbable microspheres versus hand-cut gelatin sponge particles in a porcine kidney model.

PURPOSE: To report on polyethylene glycol hydrogel-based resorbable embolization microspheres (REM) that were synthesized to resorb in < 24 hours, before inflammation and vascular remodeling, to achieve a complete arterial recanalization and to compare targeting and recanalization of REM of 300-500 µm, 500-700 µm, and 700-900 µm with hand-cut gelatin sponge particles (GSP). MATERIALS AND METHODS: Eight pigs underwent polar renal artery embolization with REM or GSP. Angiograms were obtained before embolization and 10 minutes and 7 days after embolization before pigs were sacrificed to determine the occlusion level, the percentage of occlusion, and the recanalization rate for each product. The distribution of embolic material was assessed in pathology, and infarction rate of the kidneys was measured. RESULTS: REM of 300-500 µm occluded more distal vessels than REM of 500-700 µm and 700-900 µm. At day 7, the recanalization rate was complete for the larger REM, whereas it was about 60% for the two smaller sizes. REM were completely degraded, with no residual material or inflammation. GSP occluded more proximal arteries than REM of 700-900 µm, were partly degraded at day 7, and were accompanied by a foreign body reaction in proximal and distal arteries. GSP recanalized at 79%. The infarction rate was higher with the two smaller sizes of REM and with GSP than with the largest REM. CONCLUSIONS: REM of different sizes targeted different occlusion levels in kidney arteries. GSP provided an extended occlusion level without actual targeting. Regardless of embolic material used, angiographic recanalization of renal arteries depended on the extent of necrosis. REM of 700-900 µm demonstrated the lowest infarction rate and the best recanalization rate.

Modified model of VX2 tumor overexpressing vascular endothelial growth factor.

PURPOSE: To determine whether upregulated expression of vascular endothelial growth factor (VEGF) in VX2 cells can increase vessel density (VD) and reduce tumor necrosis. MATERIALS AND METHODS: The VX2 cell line was transfected with expression vectors containing cDNA for rabbit VEGF. Stable clones producing rabbit VEGF (VEGF-VX2) were selected. VEGF-VX2 cells (n = 5 rabbits) or nontransfected VX2 cells (controls; n = 5 rabbits) were implanted into leg muscle of 10 rabbits. The animals were sacrificed at day 21. Tumor volume, percentage of necrosis, VD, and VEGF concentration in tumor protein extract were quantified. RESULTS: Overexpression of VEGF by VX2 cells augmented tumor implantation efficiency 100% and favored cyst formation. The tumor volume was significantly larger for VEGF-VX2 transfected tumors versus controls (P = .0143). Overexpression of VEGF in VX2 cells significantly increased the VD of the tumors (P = .0138). The percentage of necrosis was reduced in VEGF-VX2 tumors versus controls (19.5% vs 38.5 %; P = .002). VEGF concentration in VEGF-VX2 tumors was significantly higher than in control tumors (P = .041) and was correlated with tumor volume (ρ = .883, P = .012). CONCLUSIONS: The overexpression of VEGF increased tumor growth and vascularization, favored cyst formation, and reduced tumor necrosis. This new phenotype of the VX2 tumor may offer some advantages over classic models of VX2 tumor for evaluating anticancer therapies.

Rabbit VX2 Liver Tumor Model: A Review of Clinical, Biology, Histology, and Tumor Microenvironment Characteristics.

The rabbit VX2 is a large animal model of cancer used for decades by interventional radiologists to demonstrate the efficacy of various locoregional treatments against liver tumors. What do we know about this tumor in the new era of targeted therapy and immune-oncology? The present paper describes the current knowledge on the clinics, biology, histopathology, and tumor microenvironment of VX2 based on a literature review of 741 publications in the liver and in other organs. It reveals the resemblance with human cancer (anatomy, vascularity, angiogenic profile, drug sensitivity, immune microenvironment), the differences (etiology, growth rate, histology), and the questions still poorly explored (serum and tissue biomarkers, genomic alterations, immune checkpoint inhibitors efficacy).

Genomic Studies Across the Lifespan Point to Early Mechanisms Determining Subcortical Volumes.

BACKGROUND: Subcortical brain structures play a key role in pathological processes of age-related neurodegenerative disorders. Mounting evidence also suggests that early-life factors may have an impact on the development of common late-life neurological diseases, including genetic factors that can influence both brain maturation and neurodegeneration. METHODS: Using large population-based brain imaging datasets across the lifespan (N ≤ 40,628), we aimed to 1) estimate the heritability of subcortical volumes in young (18-35 years), middle (35-65 years), and older (65+ years) age, and their genetic correlation across age groups; 2) identify whether genetic loci associated with subcortical volumes in older persons also show associations in early adulthood, and explore underlying genes using transcriptome-wide association studies; and 3) explore their association with neurological phenotypes. RESULTS: Heritability of subcortical volumes consistently decreased with increasing age. Genetic risk scores for smaller caudate nucleus, putamen, and hippocampus volume in older adults were associated with smaller volumes in young adults. Individually, 10 loci associated with subcortical volumes in older adults also showed associations in young adults. Within these loci, transcriptome-wide association studies showed that expression of several genes in brain tissues (especially MYLK2 and TUFM) was associated with subcortical volumes in both age groups. One risk variant for smaller caudate nucleus volume (TUFM locus) was associated with lower cognitive performance. Genetically predicted Alzheimer's disease was associated with smaller subcortical volumes in middle and older age. CONCLUSIONS: Our findings provide novel insights into the genetic determinants of subcortical volumes across the lifespan. More studies are needed to decipher the underlying biology and clinical impact.

Embolization of hepatocellular carcinoma with drug-eluting beads: doxorubicin tissue concentration and distribution in patient liver explants.

BACKGROUND & AIMS: To follow the local tissue delivery of doxorubicin in HCC explants from patients embolized with drug-eluting beads and to compare it with histologic modifications. METHODS: Six patients with HCC underwent chemoembolization with doxorubicin-eluting beads (caliber 100-300 µm, dose 75-150 mg) followed by liver transplantation at different time points (8 h to 36 days). On sections of the explanted liver, the tissue concentration of doxorubicin was determined radially around bead-occluded vessels with microspectrofluorimetry. The intra/peritumoral location of the beads and the modifications of the surrounding tissue were determined on an adjacent hematein-eosin-saffron-stained section and compared to drug measurements. RESULTS: Doxorubicin was detected in the tissue surrounding the beads at all times of explantation. The drug impregnates an area of at least 1.2 mm in diameter around the occluded vessel. The tissue concentration of drug ranges from 5 µM at 8 h to 0.65 µM at 1 month. In patient transplanted at 8 h, no major tissue modification was observed and we found 42% of the beads occluding intratumoral vessels. Drug concentration was not different around intratumoral and peritumoral occluded vessels. After 9-14 days, necrosis was present around 37% of vessels and at 32-36 days, around 40% of vessels. Necrotic tissue was associated with a deeper penetration and a higher concentration of the drug than non necrotized areas, though statistically significant only at 32-36 days. CONCLUSIONS: Doxorubicin-eluting beads provide a sustained delivery of drug for a period of 1 month and local tissue concentrations above cytotoxic threshold in HCC-bearing livers.

The arterial distribution of Embozene and Embosphere microspheres in sheep kidney and uterus embolization models.

PURPOSE: To compare the in vivo distribution of the new embolic Embozene versus Embosphere as a control in the sheep renal and uterine vasculature. MATERIALS AND METHODS: Twelve sheep (three per group of product and size) were selectively embolized with Embozene 700 µm, Embozene 900 µm, Embosphere 500-700 µm, or Embosphere 700-900 µm, in one renal artery (0.5 mL microspheres) and in the two uterine arteries (0.25 mL each) and sacrificed 72 hours later for pathologic examination of kidney and uterus. Partition of microspheres in the vasculature was determined according to a classification of the renal and the uterine vasculatures into several zones. Vascular diameters and microsphere deformation were measured. RESULTS: Embozene 700 µm and Embozene 900 µm occluded significantly more distally than Embosphere 500-700 µm and Embosphere 700-900 µm in renal and uterine vasculature. For Embozene, the vessel diameter was not significantly different between the two sizes, for each organ, whereas it was significantly larger for Embosphere 700-900 µm than for Embosphere 500-700 µm in each organ. Embozene deformation was significantly higher than that of Embosphere in renal and uterine vasculature, increased from proximal to distal in location for both organs and correlated negatively with vessel diameter (Rho = -0.623; P < .0001). Embosphere deformation did not vary according to the zone. CONCLUSIONS: Embozene microspheres have a higher in vivo deformation, which results in a more distal occlusion within the vascular network compared with reference Embosphere microspheres. The diameter of occluded vessels varied for the tested size range for Embosphere but was independent of the tested microsphere size range used for Embozene. The deformation of Embozene appears to determine the size of the vessels occluded as opposed to the granulometric particle size, which makes level of occlusion unpredictable.