C.T. Loh

Advanced Hepatic Ablation Technique for Creating Complete Cell Death: Irreversible Electroporation

PURPOSE To evaluate the effectiveness of irreversible electroporation (IRE) in hepatic tissue ablation and the radiologic-pathologic correlation of IRE-induced cell death. MATERIALS AND METHODS On approval of the animal research committee, 16 Yorkshire pigs underwent ultrasonography (US)-guided IRE of normal liver. A total of 55 ablation zones were created, which were imaged with US, magnetic resonance (MR) imaging, and computed tomography (CT) and evaluated with immunohistochemical analysis, including hematoxylin-eosin (H-E), Von Kossa, and von Willibrand factor (vWF) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS At gross section examination, the mean diameter of the ablation zones was 33.5 mm + or - 3.0 (standard deviation) and was achieved in 6.9 minutes (mean total procedure time per ablation), with a mean difference of 2.5 mm + or - 3.6 between US and gross section measurements (r = 0.804). No complications were seen in any of the 16 animals. IRE ablation zones were well characterized with US, CT, and MR imaging, and real-time monitoring was feasible with US. H-E, Von Kossa, and vWF staining showed complete cell death, with a sharply demarcated treatment area. Bile ducts and vessels were completely preserved. Areas of complete cell death were stained positive for apoptotic markers (TUNEL, BCL-2 oncoprotein), suggesting involvement of the apoptotic process in the pathophysiology of cell death caused by IRE. CONCLUSION In an animal model, IRE proved to be a fast, safe, and potent ablative method, causing complete tissue death by means of apoptosis. Cell death is seen with full preservation of periablative zone structures, including blood vessels, bile ducts, and neighboring nonablated tissues.

Imaging guided percutaneous irreversible electroporation: ultrasound and immunohistological correlation.

Preliminary results of percutaneous irreversible electroporation (PIE) on swine liver as a novel non-thermal ablation are presented. The goal of this study was to evaluate the feasibility of using irreversible electroporation in more clinically applicable manner, a percutaneous method, and to investigate a possible role of apoptosis in PIE-induced cell death. We performed PIE on four swine livers under real-time ultrasound guidance. The lesions created by PIE were imaged with ultrasound and were correlated with histology data, including pro-apoptotic marker. A total of 11 lesions were created with a mean size of 16.8 cm3 in 8.4 ± 1.8 minutes. Real-time monitoring was performed and a correlation of (+) 2 ± 3.2 mm in measurement comparison between ultrasound and gross pathologic measurements was demonstrated. Complete hepatic cell death without structural destruction, unaffected by heat-sink effect, and with a sharp demarcation between the ablated zone and the non-ablated zone were observed. Immunohistological analysis confirmed complete apoptotic cell death by PIE on Von Kossa, BAX, and H&E staining. In summary, PIE can provide a novel and unique ablative method with real-time monitoring capability, ultra-short procedure time, non-thermal ablation, and well-controlled and focused apoptotic cell death.

Percutaneous Ablation of Hepatocellular Carcinoma: Current Status

Hepatocellular carcinoma (HCC) is an increasingly common disease with dismal long-term survival. Percutaneous ablation has gained popularity as a minimally invasive, potentially curative therapy for HCC in nonoperative candidates. The seminal technique of percutaneous ethanol injection has been largely supplanted by newer modalities, including radiofrequency ablation, microwave ablation, cryoablation, and high-intensity focused ultrasound ablation. A review of these modalities, including technical success, survival rates, and complications, will be presented, as well as considerations for treatment planning and follow-up.

Electron Microscopic Demonstration and Evaluation of Irreversible Electroporation-Induced Nanopores on Hepatocyte Membranes

PURPOSE To demonstrate, evaluate, and verify the existence of irreversible electroporation (IRE)-ablation induced nanopores on the plasma membrane of hepatocytes. MATERIALS AND METHODS On animal research committee approval, four New Zealand rabbits and two Yorkshire swine underwent IRE ablation of the liver (90 pulses, 100 μs per pulse at 2,500 V), and selected ablated liver tissues were harvested, fixed, and air-dried according to the electron microscopy (EM) protocol. A scanning electron microscope (SEM; Nova 230 NanoSEM [FEI, Hillsboro, Oregon] with 80 picoamperes and 10-kV acceleration) was used to visualize and verify IRE-created nanopores. Using NIH image (Bethesda, Maryland) and ImageScope (Aperio Inc., Vista, California), 21 ablated tissues (16 rabbit, 5 swine) were evaluated. Corresponding hematoxylin and eosin (H&E) evaluation was performed to verify IRE-induced cell death. RESULTS In all 21 IRE-ablated tissues, the SEM was able to show numerous, well-circumscribed, round, and concave-shaped pore defects disturbing the hepatocyte plasma membranes. These pores were not seen in normal liver. The size of the nanopores ranged from 80-490 nm with the greatest frequency of pores in bimodal distribution. The highest frequency of pore size was noted at the size range 340-360 nm. CONCLUSIONS IRE induces nanopores on hepatocyte membranes, as shown by SEM. The pore diameters are larger than nanopores created by reversible electroporation (RE), which may have implications for irreversibility or permanency.

Retrieval of Trapped Günther Tulip Inferior Vena Cava Filters: Snare–over–Guide Wire Loop Technique

The Günther Tulip inferior vena cava (IVC) filter is designed for transjugular retrieval with use of a sheath and snare device. This report describes a technique for removal of difficult-to-retrieve Günther Tulip IVC filters when the standard method fails. In a series of four patients, each with an IVC filter refractory to capture by snare alone, the use of a snare-over-guide wire loop technique succeeded in retrieving the filter in all cases.

Safety and feasibility of a novel transcervical access neuroprotection system for carotid artery stenting in the PROOF Study.

BACKGROUND Randomized controlled trials have shown that periprocedural rates of stroke and death are higher with carotid artery stenting (CAS) than with carotid endarterectomy (CEA) in the treatment of carotid artery stenosis. Diffusion-weighted magnetic resonance imaging (DW-MRI) has shown higher rates of clinically silent new ischemic brain lesions when CAS is performed as compared with CEA. The Silk Road Medical Embolic PROtectiOn System: First-In-Man (PROOF) Study is a single-arm first-in-man study using the MICHI Neuroprotection System (Silk Road Medical Inc, Sunnyvale, Calif), a novel transcervical access and cerebral embolic protection system. This system enables stent implantation under controlled blood flow reversal of the carotid artery, also known as Flow Altered Short Transcervical Carotid Artery Stenting (FAST-CAS). METHODS Between March 2009 and February 2010, a total of 44 subjects were enrolled into the study. The primary composite endpoint was major stroke, myocardial infarction, or death within 30 days. Forty-three patients (97.7%) completed the study through the 30-day endpoint. One patient was lost to follow-up. In a subgroup of consecutive subjects, DW-MRI examinations were performed preprocedure and within 24 to 48 hours after the stent implantation. Blinded independent neuroradiologists reviewed all DW-MRI studies and confirmed the absence or presence of new ischemic brain lesions. RESULTS All enrolled patients were successfully treated, and no major adverse events were seen through the follow-up period. Thirty-one subjects had DW-MRI examinations. Of these, five patients (16%) had evidence of new ischemic brain lesions but no clinical sequelae. Transient intolerance to reverse flow was reported in 9% of cases, but in all cases, a stent was successfully placed, and the intolerance was managed by minimizing the duration of reverse flow during the procedure. CONCLUSION In this first-in-man experience, FAST-CAS using the MICHI Neuroprotection System was shown to be a safe and feasible method for carotid revascularization. DW-MRI findings suggest controlled reverse flow provides cerebral embolic protection similar to that seen with CEA.

Coil-Assisted Retrograde Transvenous Obliteration (CARTO) for the Treatment of Portal Hypertensive Variceal Bleeding: Preliminary Results

OBJECTIVES:To describe the technical feasibility, safety, and clinical outcomes of coil-assisted retrograde transvenous obliteration (CARTO) in treating portal hypertensive non-esophageal variceal hemorrhage.METHODS:From October 2012 to December 2013, 20 patients who received CARTO for the treatment of portal hypertensive non-esophageal variceal bleeding were retrospectively evaluated. All 20 patients had at least 6-month follow-up. All patients had detachable coils placed to occlude the efferent shunt and retrograde gelfoam embolization to achieve complete thrombosis/obliteration of varices. Technical success, clinical success, rebleeding, and complications were evaluated at follow-up.RESULTS:A 100% technical success rate (defined as achieving complete occlusion of efferent shunt with complete thrombosis/obliteration of bleeding varices and/or stopping variceal bleeding) was demonstrated in all 20 patients. Clinical success rate (defined as no variceal rebleeding) was 100%. Follow-up computed tomography after CARTO demonstrated decrease in size with complete thrombosis and disappearance of the varices in all 20 patients. Thirteen out of the 20 had endoscopic confirmation of resolution of varices. Minor post-CARTO complications, including worsening of esophageal varices (not bleeding) and worsening of ascites/hydrothorax, were noted in 5 patients (25%). One patient passed away at 24 days after the CARTO due to systemic and portal venous thrombosis and multi-organ failure. Otherwise, no major complication was noted. No variceal rebleeding was noted in all 20 patients during mean follow-up of 384±154 days.CONCLUSIONS:CARTO appears to be a technically feasible and safe alternative to traditional balloon-occluded retrograde transvenous obliteration or transjugular intrahepatic portosystemic shunt, with excellent clinical outcomes in treating portal hypertensive non-esophageal variceal bleeding.

A New Wave in Treatment of Vascular Occlusive Disease: Biodegradable Stents—Clinical Experience and Scientific Principles

Stent-based therapies in percutaneous vascular intervention are associated with significant long-term complications related to in-stent restenosis. A growing body of literature demonstrates the feasibility of biodegradable materials for endovascular stents, which may, in theory, circumvent many of the immunologic and inflammatory response issues seen with long-term metallic stent failure in coronary and peripheral applications. This review describes the history of endovascular stents and the challenges encountered with metallic, drug-eluting, and biodegradable stents. A review of the basic engineering principles of biodegradable stents is provided, along with a discussion of the cellular mechanisms of restenosis.

A Prospective Evaluation of Cerebral Infarction following Transcervical Carotid Stenting with Carotid Flow Reversal

OBJECTIVE Cerebral embolisation constitutes the main source of complications during transfemoral carotid artery stenting (CAS) and is associated with a high incidence of silent brain infarction. The goal of this study is to evaluate the incidence of new ischaemic cerebral lesions following transcervical CAS with carotid flow reversal for neuroprotection. MATERIALS AND METHODS Thirty-one consecutive patients underwent transcervical CAS with carotid flow reversal. A stroke scale and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed within 24 h before and after the procedure. DW-MRI studies were compared blindly by two independent neuroradiologists. New hyper-intense DW signals were interpreted as ischaemic infarcts. The progress of all patients was followed for at least 30 days following intervention. RESULTS All procedures were technically successful. Nineteen (61%) patients were symptomatic Mean carotid flow reversal time was 22 min. There were no major adverse events at 30 days. All patients remained neurologically intact without increase in the stroke scale. Thirty subjects had paired DW-MRI studies. Post-procedural DW-MRI ischaemic infarcts were found in four (12.5%) patients, all ipsilateral to the treated hemisphere and asymptomatic. During follow-up, all stents remained patent and all patients remained stroke-free. CONCLUSIONS These data suggest that transcervical carotid stenting with carotid flow reversal carries a low incidence of new ischaemic infarcts, significantly lower than that reported with transfemoral CAS. The transcervical approach with carotid flow reversal may improve the safety of CAS and has the potential to produce results comparable to those of carotid endarterectomy.

Risk Factors for Developing Postprocedural Microemboli following Carotid Interventions

PURPOSE To determine risk factors predictive of microemboli found on diffusion-weighted magnetic resonance imaging (DW-MRI) following carotid angioplasty and stenting (CAS) with distal protection and carotid endarterectomy (CEA). METHODS A retrospective review was conducted of all carotid interventions at a single institution between 2004 and 2006. In that time frame, 64 carotid interventions (34 CAS, 30 CEA) were performed in 63 male patients (mean age 69.5 years, range 52 to 91) with DW-MRI scans available for review. Patient characteristics, including age, gender, smoking history, diabetes mellitus, hypertension, hyperlipidemia, obesity (body mass index >30), coronary artery disease (CAD), chronic obstructive pulmonary disease, peripheral vascular disease, and atrial fibrillation, were documented. For the CAS patients, anatomical and procedural characteristics, including fluoroscopy time, contrast volume, performance of an arch angiogram, and lesion anatomy, were recorded. Bivariate analyses were performed to determine which parameters were associated with the occurrence of acute postprocedural microemboli found on DW-MRI by 2 blinded neuroradiologists. RESULTS Twenty-four (71%) of the 34 CAS patients and 1 (3%) of the 30 CEA patients demonstrated new cerebral microemboli postoperatively. In the bivariate analyses of all patient, anatomical, and procedural characteristics, only a history of CAD was associated with an increased risk of microemboli; 20 (80%) of the 25 patients who had postprocedure microemboli had CAD compared to 18 (46%) of 39 patients without microemboli (p=0.007). Twenty (53%) of the 38 (59%) patients with CAD developed microemboli compared to 5 (19%) of the 26 patients without CAD (p=0.007). All other patient, procedural, and anatomical characteristics were not found to be independent risk factors predictive of postprocedure microemboli. CONCLUSION CAS with distal protection carries a significantly greater risk for developing new microemboli compared to CEA. Of all the risk factors analyzed, only a history of CAD emerged as an independent risk factor for the development of microemboli following carotid intervention. This finding may influence the decision to perform CAS in patients deemed high risk solely due to the presence of CAD.