Transarterial Delivery Research Articles

Bioengineered Ionic Liquid for Catheter-Directed Tissue Ablation, Drug Delivery, and Embolization.

Delivery of therapeutics to solid tumors with high bioavailability remains a challenge and is likely the main contributor to the ineffectiveness of immunotherapy and chemotherapy. Here, a catheter-directed ionic liquid embolic (ILE) is bioengineered to achieve durable vascular embolization, uniform tissue ablation, and drug delivery in non-survival and survival porcine models of embolization, outperforming the clinically used embolic agents. To simulate the clinical scenario, rabbit VX2 orthotopic liver tumors are treated showing successful trans-arterial delivery of Nivolumab and effective tumor ablation. Furthermore, similar results are also observed in human ex vivo tumor tissue as well as significant susceptibility of highly resistant patient-derived bacteria is seen to ILE, suggesting that ILE can prevent abscess formation in embolized tissue. ILE represents a new class of liquid embolic agents that can treat tumors, improve the delivery of therapeutics, prevent infectious complications, and potentially increase chemo- and immunotherapy response in solid tumors.

Trans-Arterial Stem Cell Injection (TASI): The Role of Interventional Radiology in Regenerative Medicine

Regenerative medicine is taking a step forward in treating multiple diseases. The possibility of renewing damaged tissues with stem cells has become a topic of interest in recent decades. Still a relatively new research topic, many issues in this discipline are being addressed, from cell culturing to the study of different graft materials, and, moreover, cell delivery. For instance, direct intravenous injection has a big downfall regarding its lack of precision and poorly targeted treatment. Trans-arterial and direct percutaneous infusion to the aimed tissue/organ are both considered ideal for reaching the desired region but require image guidance to be performed safely and precisely. In this context, interventional radiology becomes pivotal for providing different cell delivery possibilities in every case. In this review, we analyze different basic stem cell therapy concepts and the current and future role of interventional radiology with a focus on trans-arterial delivery.

Drug-Eluting Porous Embolic Microspheres for Trans-Arterial Delivery of Dual Synergistic Anticancer Therapy for the Treatment of Liver Cancer.

Blockage of blood supply while administering chemotherapy to tumors, using trans-arterial chemoembolization (TACE), is the most common treatment for intermediate and advanced-stage unresectable Hepatocellular carcinoma (HCC). However, HCC is characterized by a poor prognosis and high recurrence rates (≈30%), partly due to a hypoxic pro-angiogenic and pro-cancerous microenvironment. This study investigates how modifying tissue stress while improving drug exposure in target organs may maximize the therapeutic outcomes. Porous degradable polymeric microspheres (MS) are designed to obtain a gradual occlusion of the hepatic artery that nourishes the liver, while enabling efficient drug perfusion to the tumor site. The fabricated porous MS are introduced intrahepatically and designed to release a combination therapy of Doxorubicin (DOX) and Tirapazamine (TPZ), which is a hypoxia-activated prodrug. Liver cancer cell lines that are treated with the combination therapy under hypoxia reveal a synergic anti-proliferation effect. An orthotopic liver cancer model, based on N1-S1 hepatoma in rats, is used for the efficacy, biodistribution, and safety studies. Porous DOX-TPZ MS are very effective in suppressing tumor growth in rats, and induction tissue necrosis is associated with high intratumor drug concentrations. Porous particles without drugs show some advantages over nonporous particles, suggesting that morphology may affect the treatment outcomes.

Recent Advances in Interventional Fluorescence Imaging: Toward the Precise Visualization of Transarterial Mini-Invasive Delivery Systems

ConspectusInterventional fluorescence imaging has gradually developed into a promising imaging strategy for the diagnosis of diseases in clinic. This strategy could benefit interventional targeted treatment because of the clear display of microstructures at the margins and boundaries. There are some stranded crucial issues in clinical application: (i) fast clearance of fluorescence probes; (ii) light instability and photobleaching; and (iii) residual and microsatellite lesions. The development of superstable homogeneous intermixed formulation technology (SHIFT) can solve the aforementioned clinical problems for precision hepatectomy. Interventional fluorescence imaging based on SHIFT-prepared product has some advantages such as (i) strong stability, (ii) greatly extending imageable time window, and (iii) precisely visualizing microsatellite lesions. In this Account, we overview our current progress in interventional fluorescence imaging based on SHIFT method for surgical resection following long-lasting embolization conversion. To greatly realize interventional fluorescence imaging, we summarize clinical and preclinical application of interventional fluorescence imaging in a transarterial delivery system. Indeed, compared with conventional fluorescence imaging, interventional fluorescence imaging possesses non-negligible strengths on improved intensity in target location and step-down systemic toxicity. Unfortunately, a challenging issue is that immobile fluorescence performance is difficult to maintain after long-time embolization, resulting in a failed hepatectomy. On this basis, associated with our previous research, SHIFT was proposed and developed. Thus, we detailedly introduce and account the development and preponderance of SHIFT on interventional fluorescence imaging. Predictably, after lengthy embolization, its lightful fluorescence was still observable in tumor targets of a clinical trial. To regulate the fluorescence rendering of microsatellite lesion, SHIFT combining with pure nanoprobes (nanoICG) occurs, namely SHIFT nanoICG, and we dwell on its performance in transarterial invasive surgical navigation and its clinical application under interventional fluorescence imaging compared with conventional indocyanine green (ICG) formulations. Amazingly, the SHIFT nanoICG brings us an extraordinary imaging consequence for deep-seated tumor tissues and imperceptible microsatellite lesions. Finally, we offer perspectives on the future tendency of interventional imaging-guided SHIFT products in clinical translation such as chemoembolization, radioembolization, and immunotherapy. Actually, these directions have been underway for some time, and even relative products are already applied for clinical trials, exhibiting effective therapeutic outcomes. Our green high-performance SHIFT products are concentrated on meeting clinical needs and solving clinical problems, breaking through the cure limitations of patients with advanced diseases. Thus, the discovery offers insight into the development and superiority of SHIFT products under interventional fluorescence imaging and simultaneously provides a new view on the development of clinically pragmatic products.

Precise control of embolic stroke with magnetized red blood cells in mice

Precise embolism control in immature brains can facilitate mechanistic studies of brain damage and repair after perinatal arterial ischemic stroke (PAIS), but it remains a technical challenge. Microhemorrhagic transformation is observed in one-third of infant patients who have suffered PAIS, but the underlying mechanism remains elusive. Building on an established approach that uses magnetic nanoparticles to induce PAIS, we develop a more advanced approach that utilizes magnetized erythrocytes to precisely manipulate de novo and in situ embolus formation and reperfusion in perinatal rodent brains. This approach grants spatiotemporal control of embolic stroke without any transarterial delivery of pre-formed emboli. Transmission electron microscopy revealed that erythrocytes rather than nanoparticles are the main material obstructing the vessels. Both approaches can induce microbleeds as an age-dependent complication; this complication can be prevented by microglia and macrophage depletion. Thus, this study provides an animal model mimicking perinatal embolic stroke and implies a potential therapeutic strategy for the treatment of perinatal stroke.

V04-10 PURELY OFF-CLAMP ROBOT-ASSISTED PARTIAL NEPHRECTOMY FOR TOTALLY ENDOPHYTIC RENAL TUMORS: SURGICAL TECHNIQUE AND MID-TERM OUTCOMES OF A SINGLE CENTER SERIES

You have accessJournal of UrologyAdrenal & Renal Oncology I (Nephron Sparing Surgery) (V04)1 Sep 2021V04-10 PURELY OFF-CLAMP ROBOT-ASSISTED PARTIAL NEPHRECTOMY FOR TOTALLY ENDOPHYTIC RENAL TUMORS: SURGICAL TECHNIQUE AND MID-TERM OUTCOMES OF A SINGLE CENTER SERIES Gabriele Tuderti, Aldo Brassetti, Umberto Anceschi, Alfredo Maria Bove, Mariaconsiglia Ferriero, Leonardo Misuraca, Salvatore Guaglianone, Riccardo Mastroianni, Manuela Costantini, and Giuseppe Simone Gabriele TudertiGabriele Tuderti More articles by this author , Aldo BrassettiAldo Brassetti More articles by this author , Umberto AnceschiUmberto Anceschi More articles by this author , Alfredo Maria BoveAlfredo Maria Bove More articles by this author , Mariaconsiglia FerrieroMariaconsiglia Ferriero More articles by this author , Leonardo MisuracaLeonardo Misuraca More articles by this author , Salvatore GuaglianoneSalvatore Guaglianone More articles by this author , Riccardo MastroianniRiccardo Mastroianni More articles by this author , Manuela CostantiniManuela Costantini More articles by this author , and Giuseppe SimoneGiuseppe Simone More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002000.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Totally endophytic tumors represent a challenging scenario. In this context, feasibility of Off-Clamp PN is controversial. We report surgical technique, perioperative, oncologic, and mid-term functional outcomes of a single center purely off-clamp robotic PN series for totally endophytic masses. METHODS: The case of a 73-yr old male with a 3.3 cm endophytic left renal tumor was reported. Surgical steps were highlighted, focusing on ICG guide to identify the mass and margins scoring, simultaneous use of two suction devices combining irrigation and suction to maintain a bloodless and clear operative field, enucleative strategy and finally a selective renorraphy to avoid any unintentional injury to hilar branches of main vessels. Potential use of near infrared fluorescence was showed, including intravenous injection to ensure maximal preservation of healthy and functioning renal parenchyma and preoperative transarterial delivery to optimize tumor identification and resection strategy. Baseline, perioperative, oncologic and functional data were reported. RESULTS: Between January 2013 and December 2020, 56 consecutive patients with totally endophytic renal masses were treated. Median tumor diameter was 3 cm, both median PADUA and RENAL scores were 10. Median baseline eGFR was 86.4 ml/min. Median operative time was 82 minutes, and no conversion to On-clamp procedure or Radical nephrectomy was necessary in any case. Median hospital stay was 3 days. Low grade Clavien complications occurred in two patients (3.6%), high grade Clavien complication were observed in four patients (7.1%), of which one patient underwent selective arterial embolization, for post-operative bleeding, in first post-operative day; two patients underwent ureteral stent placement for urinary fistula, resolved at one-month evaluation. At thirty-day evaluation, we reported one death for acute myocardial infarction. One third of cases (32.2%) displayed a benign histotype at the final pathology.Positive surgical margins were detected in one case; 2-yr recurrence-free, cancer specific and overall survival rates were 100, 100 and 98.2 %, respectively. At a median follow-up of 24 months, newly onset of CKD stage 3b occurred in 1 single case. Median eGFR at discharge was 75 ml/min, with a median eGFR percent decrease of 10.9 %. At last follow-up median eGFR was 77 ml/min, with a median eGFR percent decrease of 5.5%. Trifecta, defined as combination of negative surgical margins, no perioperative ³3 Clavien complications and absence of significant eGFR decline (>30%), was achieved in 91% of patients. CONCLUSIONS: Purely off-clamp Robotic PN proved to be a feasible and safe surgical approach, even in totally endophytic renal tumors, providing favorable perioperative complications rate, excellent oncological outcomes, and negligible impact on renal function at mid-term follow-up. According to recent Literature, these complex cases should be considered for selective referral to high volume centers. Source of Funding: none © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e294-e294 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gabriele Tuderti More articles by this author Aldo Brassetti More articles by this author Umberto Anceschi More articles by this author Alfredo Maria Bove More articles by this author Mariaconsiglia Ferriero More articles by this author Leonardo Misuraca More articles by this author Salvatore Guaglianone More articles by this author Riccardo Mastroianni More articles by this author Manuela Costantini More articles by this author Giuseppe Simone More articles by this author Expand All Advertisement Loading ...

Transarterial Delivery of a Biodegradable Single-Agent Theranostic Nanoprobe for Liver Tumor Imaging and Combinatorial Phototherapy.

To assess selective accumulation of biodegradable nanoparticles within hepatic tumors after transarterial delivery for invivo localization and combinatorial phototherapy. A VX2 hepatic tumor model was used in New Zealand white rabbits. Transarterial delivery of silicon naphthalocyanine biodegradable nanoparticles was performed using a microcatheter via the proper hepatic artery. Tumors were exposed via laparotomy, and nanoparticles were observed by near-infrared (NIR) fluorescence imaging. For phototherapy, a handheld NIR laser (785 nm) at 0.6 W/cm2 was used to expose tumor or background liver, and tissue temperatures were assessed with a fiberoptic temperature probe. Intratumoral reactive oxygen species formation was assessed using a fluorophore (2',7'-dichlorodihydrofluorescein diacetate). Nanoparticles selectively accumulated within viable tumor by NIR fluorescence. Necrotic portions of tumor did not accumulate nanoparticles, consistent with a vascular distribution. NIR-dependent heat generation was observed with nanoparticle-containing tumors, but not in background liver. No heat was generated in the absence of NIR laser light. Reactive oxygen species were formed in nanoparticle-containing tumors exposed to NIR laser light, but not in background liver treated with NIR laser or in tumors in the absence of NIR light. Biodegradable nanoparticle delivery to liver tumors from a transarterial approach enabled selective invivo tumor imaging and combinatorial phototherapy.

“Ride the Green Light”: Indocyanine Green–marked Off-clamp Robotic Partial Nephrectomy for Totally Endophytic Renal Masses

BackgroundComplexity of robot-assisted partial nephrectomy (RAPN) mostly depends on tumor size and location. Totally endophytic renal masses represent a surgical challenge in terms of both intraoperative identification and anatomical dissection. ObjectiveTo detail a novel technique for marking preoperatively endophytic renal tumors with transarterial superselective intrarenal mass delivery of indocyanine green (ICG)-lipiodol mixture, in order to enhance surgical margins control during purely off-clamp (OC) RAPN with the use of near-infrared fluorescence imaging. Design, setting, and participantsBetween June and July 2017, 10 consecutive patients with totally endophytic renal masses underwent preoperative ICG tumor marking immediately followed by RAPN. Surgical procedurePreoperative superselective transarterial delivery of a lipiodol-ICG mixture (1:2 volume ratio) into tertiary-order arterial branches feeding the renal mass prior to transperitoneal OC-RAPN. MeasurementsClinical data were prospectively collected in our institutional RAPN dataset. Perioperative, pathological, and functional outcomes of RAPN were assessed. Results and limitationsMedian tumor size was 3cm (interquartile range 2.3–3.8). The median PADUA score was 10 (9–11). Angiographic procedure was successful in all patients. Median operative time was 75min (65–85); median estimated blood loss was 250ml (200–350). No conversion to on-clamp PN or radical nephrectomy was needed. All patients had uneventful perioperative course; median hospital stay was 3 d (2–3). At discharge, median hemoglobin (Hgb) and percent estimated glomerular filtration rate (eGFR) drop were 3.3g/dl (2.1–3.3) and 11% (10–20%), respectively. Surgical margins were negative in all cases. One-year median ipsilateral renal volume and 1-yr eGFR percent decreases were 11.7% (6–20.9%) and 12.2% (5.3–13.7%), respectively. ConclusionsWe described a novel technique to simplify challenging RAPN based on ICG superselective transarterial tumor marking. Key benefits include quick intraoperative identification of the mass with improved visualization and real-time control of resection margins. Patient summaryRobot-assisted partial nephrectomy (RAPN) for totally endophytic renal masses is a technically demanding surgical procedure, sometimes requiring radical nephrectomy. This novel technique significantly simplified surgical complexity in our Institution. Further studies with larger cohorts are warranted to confirm whether this technique provides relevant intraoperative and functional advantages.

3:00 PM Abstract No. 312 Feasibility of transarterial delivery of biodegradable nanoparticles for in vivo imaging and combinatorial phototherapy of solid organ tumors

3:00 PM Abstract No. 312 Feasibility of transarterial delivery of biodegradable nanoparticles for in vivo imaging and combinatorial phototherapy of solid organ tumors

MO-A-BRD-00: Current Trends in Y90-Microsphere Therapy: Delivery and Dosimetry

Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imaging of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: 1. To present the imaging requirements for Y90 microsphere therapy planning 2. To explain the standard dosimetry models used in Y90 microsphere therapy planning 3. To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response

MO-A-BRD-01: Clinical Perspective

Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imaging of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: 1. To present the imaging requirements for Y90 microsphere therapy planning 2. To explain the standard dosimetry models used in Y90 microsphere therapy planning 3. To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response

MO-A-BRD-02: Physics Perspective

Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imaging of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: 1. To present the imaging requirements for Y90 microsphere therapy planning 2. To explain the standard dosimetry models used in Y90 microsphere therapy planning 3. To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response

Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model.

Use of oral sorafenib, an antiangiogenic chemotherapeutic agent for hepatocellular carcinoma (HCC), is limited by an unfavorable side effect profile. Transarterial chemoembolization (TACE) employs targeted intravascular drug administration, and has potential as a novel sorafenib delivery method to increase tumoral concentrations and reduce systemic levels. This study aimed to discern the pharmacokinetics of sorafenib TACE in a rabbit VX2 liver tumor model. A 3 mg/kg dose of sorafenib ethiodized oil emulsion was delivered via an arterial catheter to VX2 liver tumors in seven New Zealand white rabbits. Following TACE, serum sorafenib levels were measured at days 0, 1, 2, 3, 7, 10, and 14 until the time of sacrifice, after which rabbit livers were harvested for analysis of sorafenib concentrations within treated tumors and normal liver. Liquid chromatography tandem mass spectrometry was used for drug quantification. Sorafenib uptake within liver tumor and nontumorous liver tissue peaked at mean 3.53 and 0.75 μg/mL, respectively, immediately post-procedure (5:1 tumor to normal tissue drug uptake ratio), before decreasing with a 10-18 hour half-life. Serum sorafenib levels peaked immediately after TACE at a mean value of 58.58 μg/mL before normalizing with a 5.2-hour half-life, suggesting early drug washout from liver into the systemic circulation. Hepatic lab parameters showed transient increase 24 hours post-TACE with subsequent resolution. While targeted transarterial delivery of sorafenib ethiodized oil emulsion shows preferential tumor uptake compared to normal liver, systemic washout occurs with a short half-life, resulting in high circulating drug levels.

Silencing of p53 RNA through transarterial delivery ameliorates renal tubular injury and downregulates GSK-3β expression after ischemia-reperfusion injury

p53, a pivotal protein in the apoptotic pathway, has been identified as a mediator of transcriptional responses to ischemia-reperfusion (IR) injury. The characteristics and functional significance of the p53 response in vivo are largely unknown in IR-induced kidney injury. Therapeutic opportunities of delivering small interfering RNA (siRNA) via venous injection have gained recognition; however, systemic adverse effects of siRNA therapy should be considered. To prevent IR-induced kidney injury, we tested the efficacy of transarterial administration of siRNA targeting p53 (p53 siRNA). Female C57BL/6 mice underwent unilateral renal artery ischemia for 30 min, followed by reperfusion. siRNA experiments utilized short hairpin (sh) RNA plasmid-based approaches. Transfection of shRNA was performed using cationic polymer transfection reagent. Injection of synthetic p53 shRNA into the left renal artery just after ischemia improved tubular injury, apoptosis, and the swelling of mitochondria in cells of the thick ascending limb of Henle (mTALH) at the outer medullary regions. Staining of upregulated p53 was colocalized with the inducible expression of glycogen synthase kinase-3β (GSK-3β) at mTALH after IR injury. p53 shRNA inhibited GSK-3β expression and restored β-catenin expression at mTALH. For IR-induced kidney injury, transarterial delivery of p53 siRNA is an effective pharmacological intervention. Targeting siRNA to p53 leads to an attenuation of apoptosis and mitochondrial damage through the downregulation of GSK-3β expression and upregulation of β-catenin. Local delivery of vectors such as p53 siRNA through a transaortic catheter is clinically useful in reducing the adverse effect of siRNA-related therapy.

First in-human intraoperative imaging of HCC using the fluorescence goggle system and transarterial delivery of near-infrared fluorescent imaging agent: a pilot study

Surgical resections remain the primary curative interventions for hepatocellular carcinoma (HCC). However, lack of real-time intraoperative image guidance confines surgeons to subjective visual assessment of the surgical bed, leading to poor visualization of small positive nodules and the extension of diffuse HCC. To address this problem, we developed a wearable fluorescence imaging and display system (fluorescence goggle) for intraoperative imaging of HCCs in human patients. In this pilot study, both intravenous (IV) and transarterial hepatic (TAH) delivery of indocyanine green (ICG) were explored to facilitate fluorescence goggle-mediated HCC imaging. The results show that all primary tumors in patients (n = 4) who received TAH delivery of ICG were identified successfully by the fluorescence goggle. In addition, 6 satellite tumors were also detected by the goggle, 5 of which were neither identifiable via preoperative magnetic resonance imaging (MRI) and computed tomography (CT) nor by visual inspection and palpation. In the group (n = 5) that received ICG intravenously, only 2 of 6 tumors visible by preoperative MRI or CT were identified with the fluorescence goggle, demonstrating the limitation of this delivery route for a non-tumor-selective imaging agent. Comparative analysis shows that the HCC-to-liver florescence contrast detected by the goggle was significantly greater in patients that received TAH than IV delivery of ICG (P = 0.013). This pilot study demonstrates the feasibility of using the fluorescence goggle to identify multifocal lesions and small tumor deposits using TAH ICG delivery in HCC patients.

MO-A-217BCD-02: Yttrium-90 Microsphere Therapy Planning and Dose Calculations

1. To understand the imaging sequence for Yttrium-90 microsphere therapy planning and dose calculations 2. To understand calculation of lung shunt fraction and estimation of absorbed dose for lung and liver 3. To become familiar with radiation safety and regulations surrounding Yttrium-90 microsphere therapy.

Abstract No. 378 EE: Direct Hepatic Artery Puncture for Transarterial Therapy in Liver Cancer

To describe the novel technique of direct percutaneous hepatic arterial puncture under ultrasound guidance as an alternative method to obtain intrahepatic arterial access in order to successfully perform two Yttrium-90 (Y90) radioembolization procedures and one transarterial embolization (TAE) procedure. Three patients with unresectable liver cancers who presented for transarterial therapy all demonstrated challenging vascular anatomy on pretreatment planning secondary to previous catheter-induced vessel injury and inherently complicated anatomic variations. These limitations prevented conventional transfemoral catheterization for the angiographic evaluation of the target lesion, assessment of surrounding vasculature, and ultimate delivery of the therapeutic agent. Ultrasound guidance was provided for direct percutaneous hepatic arterial puncture in order to gain alternative intrahepatic arterial access. When angiographic challenges prevent standard hepatic vascular access, the resources available to the interventional radiologist may allow for improvised delivery of various embolic particles via direct percutaneous hepatic arterial puncture under ultrasound guidance. The most technically difficult aspect of the procedure is the actual direct transhepatic puncture of the desired hepatic artery. The target vessel will be predominantly dictated by the patient's anatomy. The actual delivery of the radioembolic particles (Y90) via the direct percutaneous hepatic arterial system is identical to conventional transarterial delivery, except performed in a retrograde manner. Since the tip of the catheter is directed centrally, the microspheres are deposited proximally which allows natural flow dynamics to carry the particles distally (antegrade) to the tumor bed. Spherical (150-300 microns) particles were infused in the bland embolization case. The vascular anatomy and the location of the target lesion in the right liver lobe allowed for antegrade catheterization of the supplying hepatic arterial branch. The delivery of the particles was identical to conventional bland embolization and was performed until flow stagnation was achieved.

Enhancement of p53 gene transfer efficiency in hepatic tumor mediated by transferrin receptor through trans-arterial delivery

Transferrin-DNA complex mediated by transferrin receptor in combination with interventional trans-arterial injection into a target organ may be a duel-target-oriented delivery means to achieve an efficient gene therapy. In this study, transferrin receptor expression in normal human hepatocyte and two hepatocellular-carcinoma cells (Huh7/SK-Hep1) was determined. p53-LipofectAMINE with different amounts of transferrin was transfected into the cells and the gene transfection efficiency was evaluated. After VX2 rabbit hepatocarcinoma model was established, the transferrin-p53-LipofectAMINE complex was delivered into the hepatic artery via interventional techniques to analyze the therapeutic p53 gene transfer efficiency in vivo by Western blot, immunohistochemical/immunofluorescence staining analysis and survival time. The results were transferrin receptor expression in Huh7 and SK-Hep1 cells was higher than in normal hepatocyte. Transfection efficiency of p53 was increased in vitro in both Huh7 and SK-Hep1 cells with increasing transferrin in a dose-dependent manner. As compared to intravenous administration, interventional injection of p53-gene complex into hepatic tumor mediated by transferrin-receptor, could enhance the gene transfer efficiency in vivo as evaluated by Western blot, immunohistochemical/immunofluorenscence staining analyses and improved animal survival (H = 12.567, p = 0.0019). These findings show the transferrin-transferrin receptor system combined with interventional techniques enhanced p53-gene transfer to hepatic tumor and the duel-target-oriented gene delivery may be an effective approach for gene therapy.

Transcatheter Occlusion of Blalock-Taussig Shunts: Technical Options

This review of findings in children undergoing transcatheter shunt occlusion was carried out to describe and compare the results of four different embolization techniques. A retrospective review of clinical, radiologic, and cardiac catheterization records was carried out for 18 consecutive pediatric patients referred for Blalock-Taussig shunt occlusion at one institution. Technical aspects included the use of three devices--steel wire/fiber coils, detachable latex balloons, and ductal occlusion devices--and four techniques--direct transarterial placement, transarterial placement with proximal or with distal flow control, and transvenous delivery. Occlusion of the shunt was attempted in 17 patients (mean age, 6.2 years). Shunt occlusion was successful in 14 patients. Embolization of a device into the pulmonary circulation occurred in five patients, and was most frequent with transarterial delivery without flow control or with proximal flow control (in four of six). Transarterial occlusion with distal flow control and transvenous delivery of ductal occluder devices were the most reliable methods of occluding shunts without distal stenosis, with success in eight of nine cases with the former technique and all of three with the latter technique. Transarterial embolization of Blalock-Taussig shunts carries a risk of device embolization to the pulmonary circulation; this is best avoided by the use of distal flow control or transvenous placement of a ductal occlusion device.