Helen Kavnoudias

Irreversible electroporation for unresectable hepatocellular carcinoma: initial experience and review of safety and outcomes.

The aims of this study were to evaluate the safety, feasibility and tumour response of irreversible electroporation, a non-thermal ablation technique, for the treatment of unresectable hepatocellular carcinoma. The endpoints were safety and local treatment efficacy. Patients with unresectable tumours and tumours not amenable for radiofrequency ablation because of their vicinity to organs vulnerable to thermal damage such as the bowel or because they were close to large blood vessels that would limit efficacy of ablation due to the heat sink effect were treated with irreversible electroporation using percutaneous ultrasound and/or computed tomography guided electrode placement between November 2008 and December 2009. Early, late, minor and major complications were recorded. Tumour response was determined on triphasic helical computed tomography follow-up at one month, then every three months post-procedure. Eleven patients received IRE therapy to 18 HCC lesions (Mean diameter 2.44 ± 0.99 cm; range 1.0–6.1 cm) with five patients having more than one treated HCC. Mean follow-up was 18 months (range 14–24 months). Six patients required repeat treatments for local residual or recurrent disease; two of these also had IRE for distant intrahepatic recurrence. No serious complications were observed despite seven lesions lying adjacent to important structures or organs. Four patients developed transient urinary retention and seven developed transient local post-procedure pain. After IRE therapy, 13 (72%) lesions were completely ablated with 93% success for lesions <3 cm (13/14). The local recurrence-free period was 18 ± 4 months and the distance recurrence free period was 14 ± 6 months. These preliminary results suggest that IRE is a safe and feasible technique for local ablation of HCC, particularly for lesions less than 3 cm. No major complications were encountered during this study even for tumours close to essential structures or organs.

In Vivo Irreversible Electroporation Kidney Ablation: Experimentally Correlated Numerical Models

Irreversible electroporation (IRE) ablation uses brief electric pulses to kill a volume of tissue without damaging the structures contraindicated for surgical resection or thermal ablation, including blood vessels and ureters. IRE offers a targeted nephron-sparing approach for treating kidney tumors, but the relevant organ-specific electrical properties and cellular susceptibility to IRE electric pulses remain to be characterized. Here, a pulse protocol of 100 electric pulses, each 100 μs long, is delivered at 1 pulse/s to canine kidneys at three different voltage-to-distance ratios while measuring intrapulse current, completed 6 h before humane euthanasia. Numerical models were correlated with lesions and electrical measurements to determine electrical conductivity behavior and lethal electric field threshold. Three methods for modeling tissue response to the pulses were investigated (static, linear dynamic, and asymmetrical sigmoid dynamic), where the asymmetrical sigmoid dynamic conductivity function most accurately and precisely matched lesion dimensions, with a lethal electric field threshold of 575 ± 67 V/cm for the protocols used. The linear dynamic model also attains accurate predictions with a simpler function. These findings can aid renal IRE treatment planning under varying electrode geometries and pulse strengths. Histology showed a wholly necrotic core lesion at the highest electric fields, surrounded by a transitional perimeter of differential tissue viability dependent on renal structure.

Initial experience in 115 patients with the retrievable Cook Celect vena cava filter

The aim of this study was to evaluate our experience with the retrievable Cook Celect inferior vena cava (IVC) filter (William Cook, Europe) with regard to insertion, efficiency, ease of retrieval, and any associated complications. A retrospective review was performed of 115 patients (41 female, 74 male, mean age 47.97 years) who underwent Cook Celect IVC filter insertion between December 2005 and October 2007. Filter insertion was successful in all patients. Of the 115 filters inserted, 57 have been successfully retrieved (49.6%) to date. The successful retrieval rate from attempted retrieval was 93.4%. The mean dwell time of successfully retrieved filters was 114.9 days (range 14–267 days). Failed retrievals were due to a thrombosed vena cava (n = 1) and endothelialisation of the filter (n = 3). In the failed retrieval group the mean implantation time was 142 days (range 78–211 days). While this is the first retrospective clinical study on the Cook Celect filter, results to date are promising. We demonstrated an efficacious filter with a high successful retrieval rate of 93.4% and a low complication rate. The filter was assessed with extended dwell times (range 14–267 days). Failed retrieval secondary to hook endothelialisation continues to be an issue with this filter. We recognize that a limitation of our study was the lack of systematic follow‐up for clinically silent complications. Further studies to evaluate longer term outcomes and effectiveness of this filter are warranted.

Variant treatment for gastric varices with polidocanol foam using balloon‐occluded retrograde transvenous obliteration: A pilot study

Treatment of gastric variceal rupture remains difficult with current options including transjugular intrahepatic portosystemic shunt and endoscopic therapies having significant side effects or reduced efficacy. We report five cases of gastric varices that were successfully treated with balloon‐occluded retrograde transvenous obliteration of varices (BRTO) using Polidocanol foam as an alternative sclerosant to ethanolamine oleate.

Introduction to Irreversible Electroporation—Principles and Techniques

Irreversible electroporation (IRE) is a novel nonthermal focal ablation technique that uses a series of brief but intense electric pulses delivered by paired electrodes into a targeted region of tissue, killing the cells by irreversibly disrupting cellular membrane integrity. Unlike other ablation methods, IRE has relatively little effect on connective tissues and nerves and has a low patient effect. The ability of IRE to achieve cell death immediately adjacent to large vessels without effect on the vessels themselves has raised the possibility of better treatment of advanced pancreatic cancer. Because of the low effect on the patient, IRE is well suited for use in conjunction with chemotherapeutic agents. The IRE effect is not uniform and is dependent on the intrinsic conductivity of the tissue, the number of pulses delivered, the current flow achieved, and the total time for the treatment. It is currently under investigation for a wide range of solid tumors and prostate cancer in humans and in animals in the breast, brain, and spinal cord. In clinical practice, IRE can be administered either percutaneously under imaging guidance or at open operation under direct vision. In animals there is some evidence of an immune response presumably due to exposure of the intracellular target material, resulting in a greater therapeutic effect. Unlike many other cancer treatments, IRE has been introduced for human clinical use at a very early stage of development of the technique and much of the basic understanding of how and when to use IRE is still under investigation.

Hepatic Epithelioid Hemangioendothelioma Treated With Irreversible Electroporation and Antibiotics

Introduction Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm with a clinical course between benign hemangioma and angiosarcoma. It is usually defined as a lowto intermediate-grade malignancy with an overall unpredictable prognosis. WWTR1CAMTA1 gene fusion that results from a reciprocal t(1;3)(p36;q25) translocation is present in nearly all investigated EHE cases but is absent in other vascular neoplasms. Reports have described a possible correlation between Bartonella infection and hepatic EHE (HEHE), which may result from a relationship between infection, vascular endothelial growth factor induction, and angioproliferative disease. HEHE tumors are poorly responsive to chemo-, immuno-, and radiotherapy as well as several other treatment modalities. Surgical resection and transplantation are the most common treatments but present a high level of invasiveness, donor matching difficulties, and transplantation rejection issues. Furthermore, a registry study found that approximately 30% of patients who were treated with liver transplantation had recurrence in the new liver. Watchful waiting is also used, and some patients have attained stable disease for extended periods with antiangiogenics such as thalidomide and interferon alfa-2b. Irreversible electroporation (IRE) is a nonthermal focal ablation technique that involves placing needle electrodes, approximately 1 mm in diameter, into the targeted volume to deliver a series of approximately 100 brief (50 to 100 s) but intense (1 to 3 kV) electric pulses, thereby creating irrecoverable nanoscale defects in the cell membrane. This kills cells in a nonthermal manner that spares sensitive structures, including the extracellular matrix, blood vessels, and bile ducts. IRE shows promise in cancer experimental models. Treatments can be predicted with numerical modeling and monitored in real time. Complete tumor regression has been shown in animals with complex tumors, including a glioma with adjuvant radiotherapy and a large histiocytic sarcoma, which demonstrated IRE’s efficacy as a repeat therapy after cancer plasticity resulted in chemoresistance. A phase I human safety trial achieved a 66% regression rate in patients with tumors that were ineligible for or refractory to conventional cancer therapies. Here, we describe a patient with multifocal HEHE that was coincident with Bartonella infection. An antibiotic regimen was implemented for the infection, and IRE was used to treat the multiple tumor nodules. Imaging and biopsies confirmed the destruction of HEHE cancer cells by IRE within the treated volume. Case Report A 36-year-old woman presented with transient right upper quadrant pain. Hepatic lesions were noted using ultrasound followed by computed tomography (CT), magnetic resonance (MR) imaging, and positron emission tomography (PET) scans; dual-echo MR examination of the patient’s abdomen revealed multiple hypointense lesions (Fig 1A, arrows) and multiple subcentimeter nodular lesions in both lungs. A series of biopsies revealed a proliferation of cords and nests of vessels that were immunoreactive with CD31 and CD34. The lining endothelial cells were epithelioid in appearance and contained single to multiple vacuoles. Nuclei were irregular and showed some hyperchromasia, with few mitoses observed. There was an adjacent sclerosing tissue reaction. The histologic features were those of HEHE. Polymerase chain reaction analysis of the biopsies and blood samples revealed Bartonella genus bacterial DNA, as well as the reciprocal t(1;3)(p36;q25) translocation. The patient elected serial CT monitoring, during which tumor progression was noted. Following this, treatment of the tumor nodules was performed with IRE, and the Bartonella infection was treated using antibiotic therapy. For the infection, the patient underwent a 12-month regimen of both rifampicin 600 mg and azithromycin 500 mg per day. This was followed by 4 months of rifampicin 450 mg per day and doxycycline 100 mg twice per day for an additional 3 months the following year. A series of IRE procedures was performed with institutional ethics approval and informed consent from the patient. The first procedure was designed to ensure the safety of the system, and was therefore only targeted to treat the largest lesion, in liver segment 4, as visible in Figure 1A (middle arrow). Treatment was performed under general anesthesia. The electrodes were placed through a series of transintercostal insertions (Fig 1B) under CT and ultrasound guidance. A neuromuscular blockade was perfused to attenuate electrically induced muscular contraction, and electric pulses were delivered using the NanoKnife electric pulse generator system (AngioDynamics, Queensbury, NY) at a cardiac autosynchronous rate to mitigate the risk for arrhythmia. A total of five electrodes were placed at 10 distinct locations to deliver the pulses. The pulsing protocols for the first seven ablated lesions can be found in Table 1. After the patient’s recovery from anesthesia, the postoperative pain resulting from multiple transintercostal punctures was alleviated with morphine. Confirmed safety and radiographic determination of lesion response to the initial IRE procedure motivated a series of three additional procedures to treat a total of five lesions over the following 3 months; all of which were performed under general anesthesia with muscle blockade. Figure 1C shows reduced radiodensity surrounding the electrodes corresponding to the region of IRE ablation, including an additional region on the patient’s left side from a previous set of IRE pulses. Because of the hepatic capsule puncture–associated pain, all subsequent electrode placements were performed subcostally, which reduced postprocedural pain to a negligible level. Liver function enzymes after the first six IRE procedures showed marked elevation of aminotransferases that resolved in approximately 2 weeks (Fig 2). JOURNAL OF CLINICAL ONCOLOGY D I A G N O S I S I N O N C O L O G Y VOLUME 31 NUMBER 27 SEPTEMBER 2

Numerical Investigation of Hemodynamics of Lateral Cerebral Aneurysm Following Coil Embolization

Abstract Cerebral aneurysms can be treated by coil embolization within the aneurysm sac to alter the local hemodynamics and lower the wall shear stress (WSS) by making the aneurysmal flow inactive. This study investigates the hemodynamics of a lateral wall cerebral aneurysm with coils incorporating fluid-structure interaction (FSI) where the effect of apparent viscosity on thrombus formation is analysed considering the non-Newtonian behaviour of the blood. Three-dimensional transient incompressible laminar flow fields were predicted inside the aneurysm with coils at the proximal and distal neck ends with straight and curved parent vessels. The predictions showed the WSS and the effective stress were highest at the neck region, but the maximum wall displacement occurred at the dome. The coils at the distal neck performed better compared to the coils at the proximal neck in terms of reduced flow rate and higher apparent viscosity. The cerebral aneurysm with coils and curved parent vessel was subjected to higher inflow, displacement and WSS but lower apparent viscosity compared to the one with a straight parent vessel, and therefore has a greater risk of aneurysm wall damage. Hypertension increased the effective stress and displacement on the aneurysm. In patients with hypertension, more emphasis should be placed on ensuring that coils are densely packed at the distal end, especially for curved parent vessels.

Characterization of Irreversible Electroporation Ablation with a Validated Perfused Organ Model.

PURPOSE To develop and validate a perfused organ model for characterizing ablations for irreversible electroporation (IRE)-based therapies. MATERIALS AND METHODS Eight excised porcine livers were mechanically perfused with a modified phosphate-buffered saline solution to maintain viability during IRE ablation. IRE pulses were delivered using 2 monopolar electrodes over a range of parameters, including voltage (1,875-3,000 V), pulse length (70-100 µsec), number of pulses (50-600), electrode exposure (1.0-2.0 cm), and electrode spacing (1.5-2.0 cm). Organs were dissected, and treatment zones were stained with triphenyl tetrazolium chloride to demonstrate viability and highlight the area of ablation. Results were compared with 17 in vivo ablations performed in canine livers and 35 previously published ablations performed in porcine livers. RESULTS Ablation dimensions in the perfused model correlated well with corresponding in vivo ablations (R2 = 0.9098) with a 95% confidence interval of < 2.2 mm. Additionally, the validated perfused model showed that the IRE ablation zone grew logarithmically with increasing pulse numbers, showing small difference in ablation size over 200-600 pulses (3.2 mm ± 3.8 width and 5.2 mm ± 3.9 height). CONCLUSIONS The perfused organ model provides an alternative to animal trials for investigation of IRE treatments. It may have an important role in the future development of new devices, algorithms, and techniques for this therapy.

Simulation of In Vivo Irreversible Electroporation Renal Ablations

Irreversible electroporation (IRE) uses brief electric pulses to irrecoverably disrupt cell membranes, leading to cell death in a volume of tissue while leaving proteins and the extracellular matrix intact. This enables ablation without damaging blood vessels, ductal systems, and other sensitive structures. IRE has numerous indications, yet clear determination of effective lethal electric field thresholds for a number of tissues remains. In the presented work, a clinically relevant IRE electric pulse protocol is used to create focal renal ablations in canines while measuring electrical currents. Electrical data and resulting acute lesions are used to calibrate numerical models, which determined an electric field threshold of 506 V/cm (range 485 to 526 V/cm) that kills healthy renal tissue when applying a pulsing protocol of one hundred, 100 μs long pulses at a rate of one pulse per second.

Accuracy of dual bolus single acquisition computed tomography in the diagnosis and grading of adult traumatic splenic parenchymal and vascular injury

Dual Bolus Single Acquisition Computed Tomography (DBSA‐CT) has been advocated for use in trauma imaging through its ability to concurrently optimise abdominal arterial and visceral parenchymal enhancement while minimising scan times and radiation dose. However, concerns have been raised regarding excessive splenic parenchymal heterogeneity using this technique. The purpose of this study is to establish and compare the accuracy of DBSA‐CT to traditional sequential multiphase scanning techniques in the diagnosis and grading of traumatic adult splenic injury.