Chemoembolization Agents Research Articles

Cirrhotic hepatocellular carcinoma-based decellularized liver cancer model for local chemoembolization evaluation

Transarterial chemoembolization (TACE) is a common treatment for unresectable intermediate stage hepatocellular carcinoma (HCC) and involves the combination of chemotherapy agents and embolic materials to target and block the blood supply to the tumor, leading to localized treatment. However, the selection of clinical chemoembolization agents remains limited, and the effectiveness of various agents is still under investigation. Meanwhile, replicating the complex vasculature and extracellular matrix (ECM) circumstances of HCC in in vitro models for evaluating embolic agents proves to be challenging. Herein, we developed a decellularized cancerous liver model with translucent appearance, a complicated hepatic vascular system and tissue-specific ECM for the evaluation of embolic agents. Inkpad oil and microparticles were used to illustrate different systems of vascular structures between healthy and HCC rats’ livers. Quantitative analysis with AngioTool revealed significant differences in vessel density and lacunarity between the two groups. Proteomics showed higher secretion of collagens in the HCC rat liver models than in healthy livers. Utilizing this in vitro model, we investigated the impact of tumor-specific vascular structure and ECM composition on chemoembolization performance, the two key factors inaccessible by currently available drug release testing platforms. Our findings revealed that the presence of an aberrant vascular system and the distorted ECM within the model led to drug retention. This preclinical model holds great promise as a valuable tool for evaluating embolic agents and studying their performance in the tumor microenvironment. Statement of significanceTransarterial chemoembolization (TACE), which employs drug-eluting embolic agents to obstruct the tumor-feeding vessels while locally releasing chemotherapeutic drugs into the tumor, has become the first-line treatment of unresectable liver cancer over past two decades. Nevertheless, the advancement of effective drug-eluting embolic agents has been retarded due to the lack of appropriate in vitro models for assessing the local embolization and chemotherapy performances in TACE. Here we developed a cirrhotic hepatocellular carcinoma-based decellularized liver cancer model, which preserves the aberrant vasculatures and tumor-specific extracellular matrix of liver cancer, for TACE evaluation. This model incorporates a blood flow simulation component to assess the dynamics of drug release behaviors of chemoembolic agents within tumor-mimicking conditions, more accurately replicating the in vivo environment for the locoregional assessments as compared to conventional in vitro models.

Quantification and 3D Localization of Magnetically Navigated Superparamagnetic Particles Using MRI in Phantom and Swine Chemoembolization Models.

Superparamagnetic nanoparticles (SPIONs) can be combined with tumor chemoembolization agents to form magnetic drug-eluting beads (MDEBs), which are navigated magnetically in the MRI scanner through the vascular system. We aim to develop a method to accurately quantify and localize these particles and to validate the method in phantoms and swine models. MDEBs were made of Fe3O4 SPIONs. After injected known numbers of MDEBs, susceptibility artifacts in three-dimensional (3D) volumetric interpolated breath-hold examination (VIBE) sequences were acquired in glass and Polyvinyl alcohol (PVA) phantoms, and two living swine. Image processing of VIBE images provided the volume relationship between MDEBs and their artifact at different VIBE acquisitions and post-processing parameters. Simulated hepatic-artery embolization was performed in vivo with an MRI-conditional magnetic-injection system, using the volume relationship to locate and quantify MDEB distribution. Individual MDEBs were spatially identified, and their artifacts quantified, showing no correlation with magnetic-field orientation or sequence bandwidth, but exhibiting a relationship with echo time and providing a linear volume relationship. Two MDEB aggregates were magnetically steered into desired liver regions while the other 19 had no steering, and 25 aggregates were injected into another swine without steering. The MDEBs were spatially identified and the volume relationship showed accuracy in assessing the number of the MDEBs, with small errors (≤ 8.8%). MDEBs were able to be steered into desired body regions and then localized using 3D VIBE sequences. The resulting volume relationship was linear, robust, and allowed for quantitative analysis of the MDEB distribution.

Imaging response predictors following drug eluting beads chemoembolization in the neoadjuvant liver transplant treatment of hepatocellular carcinoma.

BACKGROUNDDrug-eluting bead transarterial chemoembolization (DEB-TACE) is an endovascular treatment to release chemotherapeutic agents within a target lesion, minimizing systemic exposure and adverse effects to chemotherapeutics. Therefore, identifying which patient characteristics may predict imaging response to DEB-TACE can improve treatment results while selecting the best candidates. Predictors of the response after DEB-TACE still have not been fully elucidated. This is the first prospective study performed with standardized DEB-TACE technique that aim to identify predictors of radiological response, assessing patients clinical and laboratory characteristics, diagnostic imaging and intraprocedure data of the hepatocellular carcinoma treated in the neoadjuvant context for liver transplantation.AIMTo identify pre- and intraoperative clinical and imaging predictors of the radiological response of drug-eluting bead transarterial chemoembolization (DEB-TACE) for the neoadjuvant treatment of hepatocellular carcinoma (HCC).METHODSThis is prospective, cohort study, performed in a single transplant center, from 2011 to 2014. Consecutive patients with HCC considered for liver transplant who underwent DEB-TACE in the first session for downstaging or bridging purposes were recruited. Pre and post-chemoembolization imaging studies were performed by computed tomography or magnetic resonance. The radiological response of each individual HCC was evaluated by objective response using mRECIST and the percentage of necrosis.RESULTSTwo hundred patients with 380 HCCs were examined. Analysis of the objective response (nodule-based analysis) demonstrated that HCC with pseudocapsules had a 2.01 times greater chance of being responders than those without pseudocapsules (P = 0.01), and the addition of every 1mg of chemoembolic agent increased the chance of therapeutic response in 4% (P < 0.001). Analysis of the percentage of necrosis through multiple linear regression revealed that the addition of each 1mg of the chemoembolic agent caused an average increase of 0.65% (P < 0.001) in necrosis in the treated lesion, whereas the hepatocellular carcinoma with pseudocapsules presented 18.27% (P < 0.001) increased necrosis compared to those without pseudocapsules.CONCLUSIONThe presence of a pseudocapsule and the addition of the amount of chemoembolic agent increases the chance of an objective response in hepatocellular carcinoma and increases the percentage of tumor necrosis following drug-eluting bead chemoembolization in the neoadjuvant treatment, prior to liver transplantation.

Design of Nanocomposite Injectable Hydrogels for Minimally Invasive Surgery.

Biocompatible hydrogels are materials that hold great promise in medicine and biology since the porous structure, the ability to entrap a large amount of water, and the tunability of their mechanical and tissue adhesive properties make them suitable for several applications, including wound healing, drug and cell delivery, cancer treatment, bioelectronics, and tissue regeneration. Among the possible developed systems, injectable hydrogels, owing to their properties, are optimal candidates for in vivo minimally invasive procedures. To be injectable, a hydrogel must be liquid before and during the injection, but it must quickly jellify after injection to form a soft, self-standing, solid material. The possibility to work with a liquid precursor encoding the functions that will be available after gelation allows the development of biocompatible materials that can be employed in surgery and, in particular, in noninvasive procedures. The underlying idea is to reach the target tissue by using just a needle, or by exploiting the natural body orifices, reducing surgery procedure time, induced pain, and risk of infections. Hydrogels with different properties can be obtained by changing the type of cross-linking, the cross-linking density or the molecular weight of the polymer, or by introducing pending functional groups. The introduction of a nanofiller in the hydrogel network allows for expanding the suite of the structural and functional properties and for better mimicking native tissues. In this Account, we discuss how to provide a hydrogel network with designed properties by playing with both the polymeric chains and the fillers. We present selected examples from the literature that show how to introduce stiffness, stretchability, adhesiveness, self-healing, anisotropy, antimicrobial activity, biodegradability, and conductivity in injectable hydrogels. We further describe how the chemical composition, the mechanical properties, and the microarchitecture of the hydrogel influence cell adhesion, proliferation, and differentiation. Examples of injectable hydrogels for innovative minimally invasive procedures are then discussed in detail; in particular, we showcase the use of hydrogels for tumor resection and as vascular chemoembolization agents. We further discuss how one can improve the rheological properties of injectable hydrogels to exploit them in osteochondral tissue engineering. The effect of the introduction of a conductive filler is then presented in relation to the development of electroactive scaffolds for cardiac-tissue engineering and neural and nerve repair. We believe that the rational design of biocompatible, injectable hybrid hydrogels with tunable properties will likely play a crucial role in reducing the invasiveness and improving the outcome of several clinical and surgical setups.

Improved liquid phase separation processes for generating biodegradable microspheres loaded with high concentrations of drugs for tumor embolization

ABSTRACTDrug-eluting microspheres are the most commonly used particulate embolic agents for transarterial chemoembolization of liver tumors. However, drug loading of degradable embolic particles is often insufficient. In the current study, microspheres prepared from poly(D,L-lactic-co-glycolic acid) were investigated as a biodegradable embolic agent for arterial embolization applications. Through modified solvent evaporation and liquid-induced phase separation, high drug loading (as high as 32%) and low solvent residue (as low as 0.03%) was achieved. Degradation performance, 1H NMR, and the nonsolvent’s influence on solvent residue content were assessed. These drug-loading microspheres with biodegradability hold promise for embolization therapies.

Transarterial Chemoembolization (TACE) Using Mitomycin with or without Irinotecan for Hepatocellular Carcinoma in European Patients

Background: We evaluated survival data and local tumor control in 2 groups of patients with hepatocellular carcinoma (HCC) treated with different chemotherapeutic agents for transarterial chemoembolization (TACE). Methods: 28 patients (median age 63 years) with HCC were repeatedly treated with chemoembolization at 4-week intervals. 20 patients had Barcelona Clinic Liver Cancer (BCLC) stage B, while 8 patients obtained chemoembolization for bridging purposes (BCLC stage A). In total, 98 chemoembolizations were performed (median 3.0 treatments/patient). The administered chemotherapeutic agent comprised either mitomycin only (n = 14; 50%) or mitomycin in combination with irinotecan (n = 14; 50%). Lipiodol plus degradable starch microspheres was used for all embolizations. Local tumor response was assessed by magnetic resonance imaging using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Progression-free survival (PFS) was evaluated. Results: In the mitomycin-irinotecan group, complete response (CR) was observed in 21.4%, partial response (PR) in 42.9%, stable disease (SD) in 28.6%, and progressive disease (PD) in 7.1%. In the mitomycin group, PR was observed in 57.2% of patients, SD in 21.4%, and PD in 21.4% (p = 0.043). The PFS of patients after chemoembolization with mitomycin was 4 months compared to the significantly longer PFS of 12 months in the mitomycin-irinotecan group (p = 0.003). Conclusion: Chemoembolization of HCC with mitomycin and irinotecan is the preferred treatment option for achieving local control and better PFS.

Abstract No. 514 Injectable thermo-sensitive hydrogels as chemoembolic drug delivery agents for interventional applications

Controversy exist when discussing disease control of hepatocellular carcinoma in regards to bland embolization verses drug loaded microspheres. While the reasons for the absence of convincing data supporting the use of embolic microspheres in combination with chemotherapy are multiple, the importance of achieving complete vascular occlusion and sustained drug release are clear. Therefore, the development of biodegradable injectable drug loaded materials that can “cast” the tumor capillary bed would be advantageous. Chitosan is an FDA approved biocompatible and biodegradable polysaccharide derived from the crustacean exoskeleton. It can be used as a delivery vehicle for small molecules. Chitosan was dissolved in 0.25% acetic acid solution (1.44%w/v) under magnetic stirring for approximately 12 hours at room temperature. The solution was sterilized by autoclaving at 121ºC for 30 min. Chitosan (5 mL) was mixed with 200μL of ammonium hydrogen phosphate (AHP) solution (60% aqueous solution) via two syringe vigorous mixing method. The pH of the mixture was in the range of 7-7.2. Doxorubicin (5 mg/ml) was loaded into chitosan solution during magnetic stirring for release studies. The drug released from the hydrogel was determined by measuring the concentrations of the doxorubicin after set time points with a UV-vis spectrophotometer at 483 nm with a standard curve constructed with known concentrations of doxorubicin. The resulting solution can be injected through a microcatheter with gelation times range from 1-3 minutes at 37 degrees. In vitro degradation and release studies were performed with doxorubin from the hydrogel. It was determined that the hydrogels are stable in an aqueous environment for up to 90 days. Additionally, when loaded with 5 mg/ml doxorubicin, drug release profiles demonstrated up to 70% delivery of the drug at 28 days. We hypothesized that the development of a chitosan hydrogel to enable casting and drug release can be used as an intravascular chemoembolic agent. These gels demonstrate controlled, sustained release of doxorubicin and can be injected through a microcatheter in preparation for in-vivo trials.

Transarterial Chemoembolization with Small Drug-Eluting Beads in Patients with Hepatocellular Carcinoma: Experience from a Cohort of 421 Patients at an Italian Center

PurposeTo assess the safety, tolerability, and efficacy of small drug-eluting embolic (DEE) agents (70–150 μm) for chemoembolization of hepatocellular carcinoma (HCC). Materials and MethodsThis single-center, single-arm, retrospective study involved 421 patients (mean age, 66.1 y ± 9.8 [standard deviation]) with Barcelona Clinic Liver Cancer (BCLC) stage A (n = 88), B (n = 140), or C (n = 193) HCC and Child–Pugh class A (n = 233) or B (n = 188) cirrhosis. Patients had a mean of 7.2 lesions ± 4.8 (range, 1–21; mean diameter of target lesion, 21.4 cm ± 8.1; unilobar, n = 132; bilobar, n = 289; portal vein involvement, n = 193). One (n = 320) or 2 (n = 101) vials of small DEEs loaded with doxorubicin 50 mg per vial were delivered selectively (ie, segmentally) or superselectively (ie, directly into the tumor-feeding vessel) until complete delivery or stasis/near-stasis. Treatment was repeated in patients with partial response or stable disease at 1- or 3-month follow-up (mean, 2.0 cycles ± 0.9). Adverse events within 30 days of chemoembolization, response per modified Response Evaluation Criteria In Solid Tumors (mRECIST), and survival were assessed. ResultsWithin 30 days after treatment, no deaths or bleeding events occurred, but all patients had at least 1 episode of postembolization syndrome (pain, fever, and/or nausea/vomiting; 27.1% grade 3/4 per National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0) and increased bilirubin and liver aminotransferase levels (0.2% and 5.9% grade 3/4, respectively). Overall response rates were 94.5% at 3 months and 99.5% at 6 months. Median overall survival was 42.0 months (95% confidence interval, 38.0–43.0 mo). ConclusionsChemoembolization with small DEE agents is well tolerated and an effective treatment for a broad range of patients with liver-confined HCC.

Management of neuroendocrine tumors.

Current strategies for managing neuroendocrine tumors (NETs) in adult patients are reviewed, with a focus on medication safety concerns. NETs usually originate in the gastrointestinal or bronchopulmonary tract. Symptoms due to hormonal hypersecretion often occur in patients with foregut or midgut NETs or liver metastases. Surgical resection is recommended for most localized NETs, while systemic cytotoxic chemotherapy is typically used for high-grade and pancreatic tumors. The standard of care for metastatic NETs is somatostatin analog therapy with octreotide (available in both short- and long-acting formulations) or a depot formulation of lanreotide. Everolimus and sunitinib are targeted therapies with approved indications for use in treating advanced pancreatic NETs. Some patients with liver-predominant disease or liver metastases may undergo regional chemoembolization procedures. Pharmacists should be cognizant of differences between newer and older chemoembolization agents and procedures, as well as differences between somatostatin analog products used as medications and the radiolabelled forms used in diagnostic scintigraphy. Other medication safety issues in NET management arise during perioperative supportive care, patient education, compliance counseling, and management of adverse effects of targeted therapies and chemotherapy, including stomatitis, hyperthyroidism, and hand-foot skin reaction. Somatostatin analog therapy is the mainstay for management of locally advanced or metastatic NETs. Liver-directed therapy is an option for localized unresectable disease; platinum-based chemotherapy is the first-line treatment for poorly differentiated tumors. Optimal sequencing of these treatments and targeted therapies such as everolimus and tyrosine kinase inhibitors remains to be elucidated.

Synthesis and characterisation of cationic quaternary ammonium-modified polyvinyl alcohol hydrogel beads as a drug delivery embolisation system.

To extend the platform of clinically utilised chemoembolic agents based on ion-exchange systems to support the delivery of anionic drugs, a series of PVA-based beads was produced with different levels of (3-acrylamidopropyl)trimethylammonium chloride (APTA) in their formulation. The beads were characterised to confirm composition and the effect of formulation variation on physical properties was assessed. Suspension polymerisation was shown to successfully produce uniformly spherical copolymer beads with APTA content up to 60 wt%. Equilibrium water content and resistance to compression both increased with increasing APTA content in the formulation. Confocal laser scanning microscopy was used with model drugs to demonstrate that by increasing APTA content, compounds between the molecular weight range 70–250 kDa could permeate the microsphere structures. Interaction with anionic drugs was modelled using multivalent dyes. Dyes with multi-binding sites had increased interaction with the polymer, slowing the release and also demonstrating a reduced rate of elution from beads with higher charge density. The model drug release studies demonstrate that these systems can be engineered for different potential anionic drugs for local therapeutic delivery in the clinic.

Investigation of acetylated chitosan microspheres as potential chemoembolic agents

The aim was to investigate the potential of chitosan microspheres (CMs) with different acetylation using as a chemoembolic agent. Chitosan microspheres (CMs) were prepared via water-in-oil (W/O) emulsification cross-linking method, and acetylated chitosan microspheres (ACMs) were obtained by acetylation of CMs. Next, we characterized the morphology, size, composition and degrees of deacetylation using scanning electron microscopy (TEM), dynamic laser light scattering (DLS), and Fourier transform infrared spectrometer (FTIR). All microspheres had smooth surfaces and good mechanical flexibility, and all could pass through a 5F catheter. The swelling rate (SR) of CMs decreased significantly with the increase of pH (4.0–10.0) but ACMs did not change under the same conditions. Protein absorption assays suggested that albumin was more greatly adsorbed on CMs than on ACMs. Furthermore, CMs caused more blood clots than ACMs. ACMs caused hemolysis less than CMs (<5% of the time). Data indicated that ACMs had more hemocompatibility. Cytotoxicity tests indicated that ACMs initially had less cell attached proliferation but increased with incubation. In contrast, the relative growth rate of mouse embryo fibroblasts (MEFs) on CMs decreased gradually. The results suggested that ACMs could stimulate the growth of MEFs, and CMs were not cytotoxic to MEFs. Thus, ACMs were more biocompatible with greater potential to be used as chemoembolic material.

In vitro and in vivo evaluation of chitosan microspheres with different deacetylation degree as potential embolic agent

To evaluate the potential of N-acetylated chitosan microspheres used as a chemoembolic agent in vivo and in vitro. Calibrated spherical chitosan microspheres (CMs) were prepared via Water-in-Oil emulsification method and CMs were acetylated (ACMs). The swelling rate of CMs was greatly affected by pH than that of ACMs and both of them affected by temperature. Microspheres with excellent thermal stability demonstrated controllable degradation in lysozyme solution. Doxorubicin was released from microspheres in vitro and exhibited excellent control release profile. ACMs caused hemolysis less than CMs (<5% of the time). Co-culture with mouse embryo fibroblasts revealed that microspheres have non-cytotoxic nature. Microspheres planted in a rat gluteal muscle demonstrated that it were biodegradable and biocompatible. ACMs were performed in rabbit ear embolization model and ischemic necrosis on ear was visible due to the vascular occlusion after 15 days. Acetylated chitosan microspheres could be used as potential biocompatible and biodegradable embolic agents.

Drug-Eluting Beads Loaded with Antiangiogenic Agents for Chemoembolization: In Vitro Sunitinib Loading and Release and In Vivo Pharmacokinetics in an Animal Model

PurposeThe combination of embolic beads with a multitargeted tyrosine kinase inhibitor that inhibits tumor vessel growth is suggested as an alternative and improvement to the current standard doxorubicin-eluting beads for use in transarterial chemoembolization. This study demonstrates the in vitro loading and release kinetics of sunitinib using commercially available embolization microspheres and evaluates the in vitro biologic efficacy on cell cultures and the resulting in vivo pharmacokinetics profiles in an animal model. Materials and MethodsDC Bead microspheres, 70–150 µm and 100–300 µm (Biocompatibles Ltd., Farnham, United Kingdom), were loaded by immersion in sunitinib solution. Drug release was measured in saline in a USP-approved flow-through apparatus and quantified by spectrophotometry. Activity after release was confirmed in cell culture. For pharmacokinetics and in vivo toxicity evaluation, New Zealand white rabbits received sunitinib either by intraarterial injection of 100–300 µm sized beads or per os. Plasma and liver tissue drug concentrations were assessed by liquid chromatography–tandem mass spectroscopy. ResultsSunitinib loading on beads was close to complete and homogeneous. A total release of 80% in saline was measured, with similar fast-release profiles for both sphere sizes. After embolization, drug plasma levels remained below the therapeutic threshold (< 50 ng/mL), but high concentrations at 6 hours (14.9 µg/g) and 24 hours (3.4 µg/g) were found in the liver tissue. ConclusionsDC Bead microspheres of two sizes were efficiently loaded with sunitinib and displayed a fast and almost complete release in saline. High liver drug concentrations and low systemic levels indicated the potential of sunitinib-eluting beads for use in embolization.

Society of interventional radiology critique and commentary on the cochrane report on transarterial chemoembolization

Society of interventional radiology critique and commentary on the cochrane report on transarterial chemoembolization

Transarterielle perkutane Chemoembolisation beim Leberzellkarzinom

Hepatocellular carcinoma is one of the most common cause of cancer related death. The present review gives an overview on the loco-regional therapy performed by transarterial chemoembolization (TACE).TACE combines two different therapeutic approaches. First, application of chemotherapeutic agents into tumor's feeding vessels and second, selectively de-arterialization by different particle embolization applicated during angiography. Different chemoembolization agents and techniques are described. The methode is save and less invasive. Side effects range from the postembolization syndrom with nausea, vomiting, fever and abdominal pain up to hepatic insufficiency, which is very rare.The aim of the therapy is control clinical symptoms, prolonge progression free survival, stabilize quality of life and survival. Further indications are bridging therapy prior liver transplantation and TACE is used as a neoadjuvant therapy.Thus, TACE plays a role in the therapy of HCC and indication should be tailored to the individual patient's condition by an interdisciplinary tumor board.

Liposomal doxorubicin-loaded chitosan microspheres capable of controlling release of doxorubicin for anti-cancer chemoembolization: in vitro characteristics

The aim of this study was to develop liposomal doxorubicin-loaded chitosan microspheres (LDox-CSMS) for anti-cancer chemoembolization. LDox-CSMS and doxorubicin-loaded CSMS (Dox-CSMS) devoid of liposomal carrier were prepared with an emulsification and cross-linking method. Various stirring rates were required to obtain large fractions of CSMS in the size range of 300–500 μm. Drug loading amounts were considerably influenced by the amount of doxorubicin-loaded liposomes added. Drug release from LDox-CSMS was controlled by the drug loading amount, which was varied by the addition of liposomal doxorubicin. These results indicate that LDox-CSMS can be used as an advanced chemoembolic agent that can control drug release behaviors.

In Situ Incorporation of Doxorubicin in Copolymer Particles During Suspension Polymerization

AbstractSummary: This work reports the kinetic behavior and the molecular properties of obtained copolymers during vinyl acetate and methyl methacrylate suspension copolymerizations in presence of doxorubicin. The obtained spherical particles are intended for use as chemoembolization agents. It is shown that the presence of doxorubicin in the reaction medium promotes significant changes in the copolymerization kinetics and final molecular weight averages of the polymer product.

Current status of embolic agents for liver tumor embolization

Gelatin sponge and polyvinyl alcohol particles have been the most popular particulate embolic agents for transarterial chemoembolization (TACE) of liver tumors. Over the last decade, calibrated microspheres have been introduced and increasingly used in liver tumor embolization in Western countries. In addition, drug-eluting beads (DEB) have been introduced for sustained local drug release. Such long-awaited spherical embolic agents will be introduced in Japan in the near future. The advantages of these microspheres are that particles are uniform in size and shape, and easy to inject through a microcatheter. They can travel distally to vessels corresponding to the particle size; in other words, the occlusion level can be predicted according to the particle size chosen. Thus, new bland microspheres and DEB may bring a significant advancement to embolization for primary liver tumors as well as hepatic metastases from various cancers. However, at this point, the published data suggests that both conventional TACE and DEB-TACE are equally effective for treatment of unresectable hepatocellular carcinoma, when patients are carefully selected. Therefore, indication, patient selection, and embolization techniques will be essential in order to individually adapt newer embolic agents based on oncological, anatomical and technical considerations.

Transarterial Chemoembolization Using Docetaxel-Loaded Phytantriol Cubic Phase Precursor for the Treatment of Hepatocellular Carcinoma

The purpose of this study was to evaluate the transarterial chemoembolic agent based on docetaxel-loaded phytantriol cubic phase precursor (DTX PCPP) by in vitro cytotoxicity study and in vivo evaluation of antitumor efficacy as well as the histological examination. The methythiazolyl tereazolium bromide assay in Hep G2 cell line revealed that DTX PCPP generated high cytotoxicity by causing cell apoptosis and G2/M phase arrest. In vivo studies conducted in rabbits bearing VX2 tumors, which were treated with DTX PCPP, used as a transarterial chemoembolic agent, showed a significant antitumor efficacy and prominent higher DTX concentrations in tumor and liver than those in other organs. The histology presented typical necrosis in tumor that demonstrated excellent therapeutic effect. In conclusion, the DTX PCPP could achieve an excellent antitumor effect with low systemic toxicity for the treatment of hepatocellular carcinoma and therefore implied the prospect of DTX PCPP for clinical applications.

Is prophylactic embolization of the hepatic falciform artery needed before radioembolization in patients with 99mTc-MAA accumulation in the anterior abdominal wall?

While influx of chemoembolic agents into the hepatic falciform artery (HFA) from the hepatic artery can cause supraumbilical skin rash, epigastric pain and even skin necrosis, the significance of a patent HFA in patients undergoing radioembolization is not completely clear. Furthermore, the presence of tracer in the anterior abdominal wall seen in (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) images, which is generally performed prior to radioembolization, has been described as a sign of a patent HFA. The aim of this retrospective study was to evaluate the incidence and consequences of (99m)Tc-MAA accumulation in the anterior abdominal wall, indicating a patent HFA, in patients undergoing radioembolization of liver tumours. A total of 224 diagnostic hepatic angiograms combined with (99m)Tc-MAA SPECT/CT were acquired in 192 patients with different types of cancer, of whom 142 were treated with a total of 214 radioembolization procedures. All patients received a whole-body scan, and planar and SPECT/CT scans of the abdomen. Only patients with extrahepatic (99m)Tc-MAA accumulation in the anterior abdominal wall were included in this study. Posttreatment bremsstrahlung SPECT/CT and follow-up results for at least 3months served as reference standards. Tracer accumulation in the anterior abdominal wall was presentin pretreatment (99m)Tc-MAA SPECT/CT images of 18 patients (9.3%). The HFA was found and embolized by radiologistsbefore treatment inonepatient. In the remaining patientsradioembolization was performed without any modification in the treatment plan despite the previously mentioned extrahepatic accumulation. Only one patient experienced abdominal muscle pain above the navel, which started 24h after treatment and lasted for 48h without any skin changes. The remaining patients did not experience any relevant side effects during the follow-up period. Side effects after radioembolization in patients with tracer accumulation in the anterior abdominal wall on (99m)Tc-MAA scans indicating a patent HFA are neither common nor severe. Thus, there is no absolute need for prophylactic embolization of the HFA or modification of the treatment plan if the HFA is not detectable on angiography.