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To develop a precisely calibrated, perfectly spherical, stainable, soft, and implantable but nonresorbable particulate embolization material.
Calibrated particles with a trisacryl gelatin polymer core and hydrophilic surface characteristics were obtained by reversed emulsion synthesis followed by application of a wet-sieving technique. Particles we...
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... standard deviation of particle sizes cor- related with the mesh size of the corresponding sieves (Table 1). A comparison of the average mesh size of two adjacent sieves (mesh size of sieve n plus mesh size of sieve n 1 divided by 2) and the average diameter of the collected excluded subgroup of microspheres showed a difference that progressively decreased from 150 m for the large diameters to 20 m for the small diameters. ...
Citations
... Liquid adhesives and glue have also been used for distal and proximal embolization with good efficacy [14,30], however, there are risks for polymerization [32] and reflux in non-target areas [14,30], which can cause complications, such as biloma [14]. Calibrated microspheres are more precise and suitable than glue because of their ease of delivery from the inserted microcatheter and the low levels of associated inflammation compared to other liquid embolic agents [33,34]. ...
We investigated the long-term safety and efficacy of hepatic transarterial embolization (TAE) in patients with symptomatic polycystic liver disease (PLD). Materials and Methods: A total of 26 patients were included, mean age of 52.3 years (range: 33–78 years), undergoing 32 TAE procedures between January 2012 and December 2019 were included in this retrospective study. Distal embolization of the segmental hepatic artery was performed with 300–500 µm embolic microspheres associated with proximal embolization using microcoils. The primary endpoint was clinical efficacy, defined by an improvement in health-related quality of life using a modified Short Form-36 Health Survey and improvement in symptoms (digestive or respiratory symptoms and chronic abdominal pain), without invasive therapy during the follow-up period. Secondary endpoints were a decrease in total liver volume and treated liver volume and complications. Results: Hepatic embolization was performed successfully in 30 of 32 procedures with no major adverse events. Clinical efficacy was 73% (19/26). The mean reduction in hepatic volume was –12.6% at 3 months and –27.8% at the last follow-up 51 ± 15.2 months after TAE (range: 30–81 months; both ps < 0.01). The mean visual analog scale pain score was 5.4 ± 2.8 before TAE and decreased to 2.7 ± 1.9 after treatment. Three patients had minor adverse events, and one patient had an adverse event of moderate severity. Conclusion: Hepatic embolization using microspheres and microcoils is a safe and effective treatment for PLD that improves symptoms and reduces the volume of hepatic cysts.
... Commercially, these microspheres are available in different size ranges, i.e., 40-120, 100-300, 300-500, 500-700, 700-900, and 900-1200 μm. In the early 1990s, this microsphere was developed and clinically used to treat head and neck tumors and AVMs [83]. Since FDA approval in 2000, TGMS or Embosphere has been the most popular microsphere for hypervascular tumors, AVMs, and uterine fibroid embolization. ...
... Commercially, these microspheres are available in different size ranges, i.e., 40-120, 100-300, 300-500, 500-700, 700-900, and 900-1200 µm. In the early 1990s, this microsphere was developed and clinically used to treat head and neck tumors and AVMs [83]. Since FDA approval in 2000, TGMS or Embosphere has been the most popular microsphere for hypervascular tumors, AVMs, and uterine fibroid embolization. ...
Minimally invasive endovascular embolization is a widely used clinical technique used for the occlusion of blood vessels to treat various diseases. Different occlusive agents ranging from gelatin foam to synthetic polymers such as poly(vinyl alcohol) (PVA) have been commercially used for embolization. However, these agents have some drawbacks, such as undesired toxicity and unintended and uncontrolled occlusion. To overcome these issues, several polymer-based embolic systems are under investigation including biocompatible and biodegradable microspheres, gelling liquid embolic with controlled occlusive features, and trackable microspheres with enhanced safety profiles. This review aims to summarize recent advances in current and emerging polymeric materials as embolization agents with varying material architectures. Furthermore, this review also explores the potential of combining injectable embolic agents and cell therapy to achieve more effective embolization with the promise of outstanding results in treating various devastating diseases. Finally, limitations and challenges in developing next-generation multifunctional embolic agents are discussed to promote advancement in this emerging field.
... Many authors have performed PAE with trisacryl gelatin spherical particles (1,2,5,6,8,9). Their decreased size variability and aggregation have reportedly led to more predictable target occlusion (11)(12)(13). The 100-300-μm version of these particles could potentially penetrate prostate tissue better and cause superior infarction than larger particles. ...
Purpose:
To report medium-term outcomes of prostatic artery embolization (PAE) using 100-300-μm trisacryl gelatin microspheres to treat lower urinary tract symptoms (LUTS) from benign prostatic hyperplasia (BPH) and to evaluate how cone-beam computed tomography-measured prostate gland volume (PGV), median lobe enlargement (MLE), age, and Charlson Comorbidity Index (CCI) affect these results.
Materials and methods:
Seventy-four consecutive patients who underwent PAE from April 2014 through August 2018 were retrospectively reviewed. Patients had International Prostate Symptom Score (IPSS) >12, Quality of Life (QoL) score >2, prostate gland volume (PGV) >40 mL, age older than 45 years, and medical therapy failure. Twelve patients were excluded for bladder pathology or prostate cancer. Patients (n = 62, age = 71.8 ± 9.3 years, CCI = 3.5 ± 1.7, PGV = 174 ± 110 mL) had pre-procedure IPSS = 22.4 ± 5.6, QoL score = 4.4 ± 0.9, and post-void residual (PVR) = 172 ± 144 mL. Post-procedure values were compared to baseline at 1, 3, 6, 12, and 24 months. Associations between outcomes and PGV, MLE, age, and CCI were evaluated. Adverse event recording used Clavien-Dindo classification.
Results:
One month after PAE (n = 37), IPSS improved to 7.6 ± 5.2 (P < .0001) and QoL score improved to 1.7 ± 1.4 (P < .0001). At 3 months (n = 32), improvements continued, with IPSS = 6.4 ± 5.1 (P < .0001), QoL score = 1.2 ± 1.2 (P < .0001), PVR = 53 ± 41 mL (P < .001), and PGV = 73 ± 38 mL (P < .0001). Results were sustained at 6 months (n = 35): IPSS = 6.4 ± 4.1 (P < .0001), QoL score = 1.2 ± 1.2 (P < .0001), PVR = 68 ± 80 mL (P < .0001), PGV = 60 ± 19 mL (P < .001). At 12 months, patients (n = 26) had IPSS = 7.3 ± 5.5 (P < .0001), QoL score = 1.2 ± 0.8 (P <.0001), PVR = 89 ± 117 mL (P < .0001), PGV = 60 ± 48 mL (P < .01). At 24 months, patients (n = 8) had IPSS = 8.0 ± 5.4 (P < .0001), QoL score = 0.7 ± 0.5 (P < .0001), PVR = 91 ± 99mL (P = 0.17), and PGV = 30 ± 5mL (P = .11). Improvements were independent of PGV, MLE, age, and CCI. Two grade II urinary infections occurred.
Conclusions:
PAE with 100-300-μm microspheres produced sustained substantial improvements in LUTS, PGV, and PVR, which were independent of baseline PGV, MLE, age, or CCI.
... TG-ms consist of a trisacryl matrix with embedded gelatin. [159] Trisacryl polymer has long been used as base material in chromatography-column manufacture for protein filtration due to its low porosity and biocompatibility. [159,160] The impregnated gelatin allows cell growth and spreading. ...
... [159] Trisacryl polymer has long been used as base material in chromatography-column manufacture for protein filtration due to its low porosity and biocompatibility. [159,160] The impregnated gelatin allows cell growth and spreading. [159] TG-ms can be synthesized from a reversed emulsion process, followed by wet sieving for size selection. ...
... [159,160] The impregnated gelatin allows cell growth and spreading. [159] TG-ms can be synthesized from a reversed emulsion process, followed by wet sieving for size selection. [159,160b] TG-ms obtained from this methodology appear spherical, exhibit smooth contours, and are homogenously distributed. ...
Minimally invasive transcatheter embolization is a common nonsurgical procedure in interventional radiology used for the deliberate occlusion of blood vessels for the treatment of diseased or injured vasculature. A wide variety of embolic agents including metallic coils, calibrated microspheres, and liquids are available for clinical practice. Additionally, advances in biomaterials, such as shape‐memory foams, biodegradable polymers, and in situ gelling solutions have led to the development of novel preclinical embolic agents. The aim here is to provide a comprehensive overview of current and emerging technologies in endovascular embolization with respect to devices, materials, mechanisms, and design guidelines. Limitations and challenges in embolic materials are also discussed to promote advancement in the field. Advances in biotechnology and material science have facilitated the development of embolic agents for vascular embolization. Both clinical and preclinical embolic agents, including mechanical occlusion devices, particulates, and liquids, are reviewed. The challenges and future insights in this field are also highlighted. An integrated and multidisciplinary approach may offer opportunities to revolutionize the next generation of embolic agents.
... 19 However, this has mostly been replaced by nonbiodegradable TG microspheres which can occlude very distal tumorsupplying blood vessels. 20 While no consensus exists about the number of cTACE procedures that are needed to achieve satisfactory treatment, at least two sessions should be performed before treatment is abandoned or alternative therapies are considered. 21 Multiple TACE procedures can be administered either at regular intervals (on schedule) or when there is poor tumor response or disease progression (on demand). ...
Hepatocellular carcinoma is the second most common cause of cancer-related deaths worldwide. Along with viral and alcoholic hepatitis, obesity is the leading cause for increasing incidence in the western world, specifically in the United States. As most patients initially present with intermediate to advanced stage disease, curative therapies such as ablation, surgical resection, or liver transplantation cannot usually be applied. Thus, intra-arterial therapies (IATs), such as transarterial chemoembolization (TACE), have become a mainstay of treatment. Several variations of transarterial embolotherapy, such as bland transarterial embolization or drug-eluting bead TACE, are currently available and used in clinical practice. However, no clear guidelines or evidence exist that would favor one of these options over the other, leaving the decision-making process open to influence by local expertise and experience. In addition, combining TACE with systemic antiangiogenic agents, such as the multityrosine kinase inhibitor sorafenib, has been investigated in several prospective clinical trials without clearly demonstrating substantial survival benefits of the combination over TACE alone. This review will summarize and discuss the available clinical evidence and indications for each treatment modality with the goal of facilitating clinical decision-making processes, and provide an overview of the ongoing efforts to compare different IAT modalities.
... As previously reported, the injection of our system was easy and there was no obstruction by its passage through the narrow catheter used in the ex vivo model. One of the most important limits of TAE is related to clogging of the catheter due to the tendency of microparticulate material to aggregate [45]. In the case of the present systems, the obstruction of the catheter was avoided because a liquid emulsion formulation was injected and hardening of microglobules takes place only after they come into contact with body fluids. ...
Background: In situ forming biodegradable poly(ε-caprolactone) (PCL) microspheres (PCL-ISM) system was developed as a novel embolic agent for transarterial embolization (TAE) therapy of hepatocellular carcinoma (HCC). Ibuprofen sodium (Ibu-Na) was loaded on this platform to evaluate its potential for the treatment of post embolization syndrome.
Methods: The influence of formulation parameters on the size/shape, encapsulation efficiency and drug release was investigated using mixture experimental design. Regression models were derived and used to optimize the formulation for particle size, encapsulation efficiency and drug release profile for TAE therapy. An ex vivo model using isolated rat livers was established to assess the in situ formation of microspheres.
Results: All PCL-ISM components affected the studied properties and fitting indices of the regression models were high (Radj² =0.810 for size, 0.964 encapsulation efficiency, and 0.993 or 0.971 for drug release at 30min or 48h). The optimized composition was: PCL=4%, NMP=43.1%, oil=48.9%, surfactant=2% and drug=2%. Ex vivo studies revealed that PCL-ISM was able to form microspheres in the hepatic arterial bed.
Conclusions: PCL-ISM system provides a novel tool for the treatment of HCC and post-embolization syndrome. It is capable of forming microspheres with desirable size and Ibu-Na release profile after injection into blood vessels.
... 22 They are commercially available in a pre-mixed form offering several ranges of well calibrated particle size. 23 At the time of their commercial introduction, the provided sizes were chosen theoretically to match the size ranges of arterioles detectable by angiography and accessible to selective catheterization. Three commonly used US Food and Drug Administration approved brands -Embosphere, Bead Block and Embozene ( Figure 2)share the following properties: a compressible microsphere made of an acrylic core (trisacryl, acrylamido-PVA and polymethylmethacrylate, respectively) and a hydrophilic coating (a water-insoluble polymer connected in a three-dimensional framework, or hydrogel). ...
... Three commonly used US Food and Drug Administration approved brands -Embosphere, Bead Block and Embozene ( Figure 2)share the following properties: a compressible microsphere made of an acrylic core (trisacryl, acrylamido-PVA and polymethylmethacrylate, respectively) and a hydrophilic coating (a water-insoluble polymer connected in a three-dimensional framework, or hydrogel). [23][24][25][26][27] The safety of microspheres in head applications was reported in a prospective case series of 55 patients compared with a historical control, in which large size 400 mm calibrated Embozene microspheres were associated with no intracranial hemorrhage following meningioma embolization, conferring to them a safety profile unlike any previously published safety data. 28 Although fragmentation was not observed following suspension and manipulation of microsphere particles, they were shown to be easily deformed by a needle or indented by other particles. ...
Endovascular particle embolization is a common procedure with a relatively safe profile. We report here four cases in which cranial nerves, skin and mucosal ischemic complications occurred with the use of hydrogel microspheres (250–500 µm in size). Given the compressibility and higher penetration potential of microsphere particles compared with polyvinyl alcohol particles of similar size, we suggest oversizing hydrogel microsphere particles for head and neck embolizations.
... The trisacryl gelatin MS, Embosphere® (Merit Medical Systems), was originally developed in the early 1990s and is a copolymer of a N-tris-hydroxymethyl methylacrylamide monomer, a diethylaminoethylacrylamide monomer, and a N,N-methylenebis-acrylamide monomer [94][95][96]. The polymerization is followed by a stage of reticulation with gelatin. ...
Percutaneous transcatheter embolization procedures involve the selective occlusion of blood vessels. Occlusive agents, referred to as embolics, vary in material characteristics including chemical composition, mechanical properties, and the ability to concurrently deliver drugs. Commercially available polymeric embolics range from gelatin foam to synthetic polymers such as poly(vinyl alcohol). Current systems under investigation include tunable, bioresorbable microspheres composed of chitosan or poly(ethylene glycol) derivatives, in situ gelling liquid embolics with improved safety profiles, and radiopaque embolics that are trackable in vivo. This article reviews commercially available materials used for embolization as well as polymeric materials that are under investigation.
... The inclusion and exclusion criteria used in selecting the procedures were: i) target population: premenopausal adult patients with symp- PVA through a microcatheter, and clumping of particles that makes the effective size of PVA larger than the actual size, leading to embolic occlusion that is more proximal than intended [10,[17][18][19]. Therefore, spherical PVA was developed against the tendency to clump and obstruct microcatheters. ...
This study is to compare the outcomes of tri-acryl gelatin microspheres (TAGM) and polyvinyl alcohol (PVA) in the treatment of uterine myomas with uterine artery embolization (UAE). Meta-analysis was performed by electronic literature searches from databases including Cochrane Central Register of Controlled Trials, PubMed, EMBASE and meta Register of Controlled Trials for studies published prior to December 2014. Randomized controlled trials comparing TAGM and PVA treating uterine myomas were included in the analysis. Information retrieved from each study included study design, number of participants, study settings, patient characteristics, sample size, follow-up duration and outcomes. Imaging outcomes and clinical outcomes were the main criteria for the evaluation of the included studies. Twenty-eight articles published from 1966 to December 2014 were retrieved through database searching and other sources. After initial screening and assessment, five randomized controlled trials, including 309 women with uterine myomas, met the inclusion criteria. In both imaging and clinical outcomes, TAGM group showed superior or similar effects than PVA group. The results showed more number of patients with significant tumor enhancement, greater mean change in tumor volume, greater mean changes in symptom score and QOL score in TAGM group compared with PVA group, with significant differences. TAGM and PVA groups had similar uterine volume, mean changes in bleeding score and pain score. TAGM is better than PVA as an embolic agent in the treatment of uterine myomas with UAE.
... In 1996, Laurent et al. [13] reported the development Note: Dosage (mL) is the volume of microspheres; the actual dosage is the volume of microspheres multiplied by the dilution ratio. ...
Objective:
To investigate the efficacy and safety of transarterial embolization (TAE) using embolization microspheres in the treatment of non-hypervascular malignant liver tumors.
Methods:
Patients with malignant non-hypervascular liver tumors, who were treated with TAE using embolization microspheres, were selected and analyzed retrospectively. The technical success rate, tumor response, and complications were assessed.
Results:
Six patients were included in the study: 1 patient each with hepatocellular-cholangiocarcinoma, intrahepatic cholangiocarcinoma, hepatic metastasis after resection of common bile duct carcinoma, liver metastasis from colon cancer, liver metastasis from esophageal cancer, and liver metastasis from pancreatic cancer. The technical success rate was 100%. At 1 and 3 months after TAE, tumor local reactions were seen in 6/6 and 2/6 patients, respectively, and the tumor necrosis rates were 48%-73% and 22%-68%, respectively. The main complications were those related to the embolization syndrome, including 1 case of liver abscess and 1 case of severe pain on the first day after embolization.
Conclusion:
TAE with embolization microspheres is safe and effective in non-hypervascular liver tumors. It is a feasible option for palliative therapy of these tumors.
