Original Scientific Paper
Eur Surg (2009) 41/3: 104–108 DOI 10.1007/s10353-009-0463-z © Springer-Verlag 2009
surgery
european
ACA Acta Chirurgica Austriaca Printed in Austria
Initial data on a novel endovascular radiofrequency catheter when used for arterial occlusion in liver cancer
S. E. Khorsandi1 , P. Kysela1;2 , V. Valek2 , O. M. S. Olufemi3 , I. Lázár3, V. Prochazka4 , D. Zacharoulis5 , C. Rountas5 , N. A. Habib1;6
1 2
Department of Biosurgery and Surgical Technology, Imperial College London, London, UK Department of Radiology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic 3 Borsod County Teaching Hospital, Miskolc, Hungary 4 Department of Surgery, University Hospital Ostrava, Czech Republic 5 Department of Surgery, University Hospital of Larissa, Larissa, Greece 6 EMcision Ltd., London, UK Received May 10, 2009; accepted after revision May 19, 2009
Neue Methode zur Gefäßversiegelung mittels Radiofrequenz-Energie bei Lebertumoren
Zusammenfassung. Grundlagen: Wir untersuchten die ¨ Sicherheit und Wirksamkeit eines neuen endovaskularen ¨ Radiofrequenzkatheters (VesCoag) fur den Arterienverschluss beim Management von Lebertumoren. Methodik: Die Patienten hatten einen nicht resekta¨ ¨ ¨ blen primaren oder sekundaren Lebertumor. Der primare ¨ Endpunkt war, ob VesCoag in das Zielgefaß eingebracht ¨ werden konnte, der sekundare Endpunkt, ob es zu einem ¨ften Verschluss des Gefaßes kam. ¨ Angiographie-gepru Ergebnisse: VesCoag wurde bei 13 Patienten ¨ angewendet (4 Metastasen, 7 hepatozellulare Karzinome, 2 intrahepatale Gallenganskarzinome). In allen ¨ Fallen konnte VesCoag ohne Komplikation (Ruptur, ¨ Dissektion) in die Zielgefaße eingebracht werden. Die Durchleuchtungszeit betrug 12,86 min, die Sondenaktivierung 240 (20–600) sec. Die abgegebene Energie betrug 2 W–120 W. Die bipolare Radiofrequenz konnte ¨ ¨ in keinem Fall einen adaquaten Gefaßverschluss erzielen, deshalb wurde der monopolare Modus verwendet. 4mal kam es zu Schmerzen, ein angiographisch nach¨ gewiesener Verschluss wurde in 11 Fallen erzielt. 12 ¨ der 13 Patienten erhielten eine weiterfuhrende Therapie (10Â Chemoembolization, 1Â Chemotherapie, 1Â Lipiodol). Schlussfolgerungen: Diese erste Erfahrung mit VesCoag zeigt, dass die Methode sicher ist und einen geziel¨ ten Verschluss von Zielgefaßen erlaubt.
¨sselworter: Lebertumore, ¨ Schlu versiegelung.
¨ Radiofrequenz, Gefaß-
Correspondence: Professor Nagy Habib, ChM, FRCS, Head of Biosurgery and Biotechnology, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. Fax: þþ44-20-8383 3212 E-mail: nagy.habib@imperial.ac.uk
Summary. Background: To assess the safety and effectiveness of a newly designed endovascular radiofrequency (RF) catheter (VesCoag) when used for arterial occlusion in the management of liver cancer. Methods: Patients considered for the study had either primary or secondary cancer of the liver, which was not suitable for initial surgical resection. The primary endpoint of the study was whether VesCoag could be manipulated into the target blood vessel and the secondary endpoint was whether on angiography the blood vessel had been sealed. Results: VesCoag was used in 13 patients. The indications for treatment were metastatic disease in 4, hepatocellular carcinoma in 7, and intrahepatic cholangiocarcinoma in 2. In all cases, VesCoag was manipulated into the target vessel for activation. There were no technical problems such as vessel dissection or rupture. The average fluoroscopic time was 12.86 min and the mean duration of probe activation was 240 (range 20–600) seconds. The lowest wattage used was 2 W and the highest 120 W. In no cases was bipolar radiofrequency activation sufficient to produce vessel sealing, so monopolar mode was used throughout. There were four minor complications of pain. The angiographic endpoint of target vessel occlusion was achieved in 11 patients. In 12 out of 13 cases an additional endovascular therapeutic maneuver was performed after VesCoag activation. These additional therapies were chemoembolization n ¼ 10, chemotherapy n ¼ 1, and lipiodol n ¼ 1. Conclusions: This early assessment of VesCoag shows it to be safe and fulfill its design remit of being able to produce precise occlusion of the targeted vessel. Keywords: Radiofrequency, endovascular, liver cancer.
Initial data on a novel endovascular radiofrequency catheter
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Original Scientific Paper
Introduction
It is estimated that only 20–30% of patients who present with liver cancer are able to undergo surgical resection [1]. The liver has a dual blood supply, with 80% derived from the portal vein (PV) and the remainder from the hepatic artery (HA). Both primary and secondary liver tumors are mainly supplied arterially and arterial occlusion can be exploited to palliate or retard tumor growth [2]. In a sub group of patients, where this has been performed subsequent hepatic resection may then become feasible [3]. This strategy has the clinical potential to be used in a variety of solid tumors outside and within the liver, where it already has an established role in the management of Hepatocellular Carcinoma (HCC) [4]. Presently available endovascular techniques to occlude the tumor arterial blood supply rely on the delivery of embolic material, which may or may not be combined with chemotherapy. From the data available on HCC where this strategy has been used, there is no evidence as yet to say that transarterial chemoembolization (TACE) is therapeutically superior to a bland transarterial embolization (TAE), neither is there clinical data to suggest that one embolic material over the other has any advantage [5]. One recognized disadvantage in the use of embolic material, is the risk of collateral damage to non target tissue resulting in the morbidity of this therapeutic strategy. In the context of HCC, embolization of non tumoral liver can lead to liver failure and other non target organ complications such as cholecystitis, and upper gastrointestinal bleeding, and it is this potential collateral injury that determines the procedural related mortality of therapeutic embolization [5, 6]. To try and address some of the problems of embolization and to increase therapeutic precision, an endovascular radiofrequency catheter was developed. The development of a radiofrequency catheter to produce precise sealing of blood vessels may prove to be an alternative to therapeutic embolization in a number of clinical scenarios. The purpose of this article is to report the safety and effectiveness of this newly designed endovascular radiofrequency (RF) catheter (VesCoag) when used for arterial occlusion as part of the multimodal management of primary and secondary cancers of the liver.
Data collected included patient characteristics such as gender, age, and fitness using the American Society of Anesthesiolgy (ASA) classification. Tumor data collected included cancer type and treated lesion diameter (cm). Procedural data collected was therapeutic strategy (e.g., VesCoag use combined with chemoembolization), fluoroscopic screening time, duration and wattage (W) of VesCoag activation. All complications during and post procedure were also recorded. Description of device and procedure VesCoag (Emcision Ltd., London, UK) is a RF endovascular catheter (5 F, length 110 cm) that can be inserted over a standard guide wire (0.014 inch) into either artery or vein. At the tip of the catheter are two platinum ring electrodes (Fig. 1). When activated in bipolar mode a high frequency current runs between these two electrodes to heat and coagulate the blood vessel wall to result in it being sealed. VesCoag also has the facility to be used in monopolar mode, where a grounding pad is then required to allow the high frequency current to run from the active electrodes at the tip of the VesCoag catheter to the grounding pad. The two alternative radiofrequency generators that can be used to power VesCoag are Radionics Cosman Coagulator CC-1 and RITA Medical Systems 1500. At the start of the procedure the RF generator was initially switched on and put into standby mode. VesCoag was then introduced into the femoral artery using a standard Seldinger technique over a 0.014-inch guidewire. Under fluoroscopic control, VesCoag was then manipulated until its position was confirmed in the target vessel. The RF generator was then activated, initially using the lowest power setting of 1 Watt (W) to start endovascular vessel coagulation. Power was applied for 2 min or until an increase in impedance of 10% over baseline was observed, this increase in impedance indicating that the vessel tissue had been heated sufficiently for endovascular tissue coagulation to occur. If an appropriate increase in impedance had not been observed, the wattage was increased and power reapplied for another two-minute duration or until impedance had increased by 10% [7]. When sufficient
Methods
Patients For this pilot clinical study, the declaration of Helsinski was adhered to throughout and the protocol approved by the local ethics committee. Informed consent was obtained from all participating patients. Patients considered for inclusion in the study had primary or secondary cancer of the liver, which were not suitable for initial surgical resection. Criteria used to decide on whether surgical resection of the liver tumor was feasible were patient’s fitness to tolerate a general anesthestic, anatomic location of disease in relation to blood vessels=bile duct and underlying liver synthetic function. Decision for unresectability and for VesCoag use was discussed and decided upon at a multidisciplinary meeting.
Initial data on a novel endovascular radiofrequency catheter
Fig. 1: Close up of the radiofrequency vascular catheter (VesCoag) showing the two platinum ring electrodes at its tip
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heating of the vessel had been achieved the RF generator was placed into stand by mode or turned off. VesCoag was then retracted by 2–3 cm, this was done gently so as not to avulse coagulated tissue and after 2 min a completion angiogram was performed to document the effect of VesCoag on the vessel. If on angiography the vessel had not be sealed, VesCoag was then reapplied ensuring a good contact between target vessel endoluminal surface and the RF catheter to allow uniform heating. If clinically indicated, an additional endovascular therapeutic maneuver was then performed at the same interventional session, using the central channel of the VesCoag catheter for the delivery of chemotherapy, lipiodol, or embolic material.
patient was 68.5 years (range 48–80), five patients were female and eight were male. The indications for treatment were metastatic disease in 4, HCC in 7, and intrahepatic cholangiocarcinoma in 2 (Table 1). The mean diameter of the lesion targeted with VesCoag was 8.1 cm (range 2–18). The fitness of the majority of patients selected for VesCoag treatment based on the ASA score were ASA II n ¼ 3, ASA III n ¼ 8, and ASA IV n ¼ 2. Of the patients with HCC four were Child A and three Child B (Table 1). Procedural data: technical success, morbidity, and mortality In all cases VesCoag was manipulated into the target vessel for RF catheter activation. There were no technical problems such as vessel dissection or rupture. The average fluoroscopic time was 12.86 min and the mean duration of RF catheter activation was 240 (range 20–600) seconds. The lowest wattage used was 2 W and the highest 120 W (Table 1). In no cases was bipolar RF activation found to be sufficient to produce vessel sealing on angio-
Results
Patient demographics and tumor characteristics In this small series (n ¼ 13), VesCoag was used to occlude the tumor arterial blood supply. The average age of the
Tab. 1: Summary of clinicopathological data and therapeutic interventions on patients treated with VesCoag Age Sex Tumor ASA Child Size Duration Power Procedural AngioAdditional LOS (cm) of (W) compligraphic therapy activation cations vessel (sec) occlusion
72 59 48 69 70 80 79 72 65 72 63 74 68 F M M F F M M F M M M F M RCC HCC CC HCC CLM HCC CLM HCC HCC Larnygeal HCC CC HCC 2 3 3 3 2 3 3 3 3 2 3 4 4 n=a A n=a B n=a B n=a B A n=a A n=a A 5.1 5 13 8 5.5 3.7 2 2 7 2.2 10 18 15.6 215 156 130 66 20 20 240 240 600 480 360 180 240 20–60 20–60 40 40 40 40 10–40 10–40 25–60 60–120 35–50 2 2 none none none none none none pain pain pain none pain none none Y Y Y Y N Y Y N Y Y Y Y Y chemotherapy and lipiodol chemotherapy þ DC chemotherapy and lipiodol chemotherapy þ DC chemotherapy þ DC None chemotherapy and lipiodol lipiodol chemotherapy and lipiodol chemotherapy and lipiodol chemotherapy and lipiodol chemotherapy þ coils chemotherapy þ PVA 1 2 1 2 2 2 1 2 1 1 1 6 5
Tumor type: renal cell metastases (RCC), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CC), and colorectal liver metastases (CLM). Fitness of patient recorded using the American Society of Anesthesiology (ASA) classification. When a HCC patient Child classification used, otherwise not applicable (n=a). Size refers to diameter of lesion treated (cm). Power VesCoag used as recorded in Watts (W) and the duration of its activation in seconds. VesCoag procedural complications and occlusion of targeted vessel on angiography after VesCoag therapy is summarized. Additional therapies used with VesCoag were polyvinlyalcohol (PVA) and doxorubicin coated beads (DC). Length of stay (LOS).
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graphic assessment, so VesCoag was used in monopolar mode in all patients. There were four minor complications of pain related to the use of VesCoag, the wattage level of RF catheter activation in these cases was 40–60 W and duration of RF catheter activation ranged from 4 to 10 min. In one case, the level of pain necessitated the procedure to being abandoned in this case the RF catheter had been activated for the longest time period of 10 min at 40 W (Table 1). The angiographic endpoint of target vessel occlusion was achieved in 11 patients (Fig. 2a and b). In two cases there was failure of vessel occlusion, one case was related to the procedure being stopped prematurely because of pain and in the second case the probe had only been activated for a short time period of 20 sec at 40 W. In 12 out of 13 cases an additional endovascular therapeutic maneuver was performed. These additional therapies were chemoembolization n ¼ 10, chemotherapy n ¼ 1, and lipiodol n ¼ 1 (Table 1). The median length of stay (LOS) after endovascular therapy was 2 (range 1–6) days. The two patients who had a LOS greater than 2 days, had the largest tumor diameters treated, of 18 cm (intrahepatic cholangiocarcinoma) and 15.6 cm (HCC), both cases had been chemoembolized after VesCoag treatment and then required an in patient stay of 6 and 5 days, respectively
(Table 1). There were no cases of deterioration in liver function tests post procedure and there were no 30 days procedural deaths.
Discussion
A number of different transarterial techniques have been developed to palliate or assist in the multimodal management of liver tumors and it is a rapidly expanding field, as the indications for transarterial therapies broaden. A recent review of transarterial therapeutic procedures in the context of HCC concluded that TAE is as effective as TACE but that newer strategies are required to reduce post TACE=TAE complications [5]. Developing and comparing different transarterial therapeutic techniques is presently difficult because of the clinical heterogeneity and lack of standardization between the published series, even when one cancer type is considered such as HCC. Additionally, objective imaging endpoints such as the response evaluation criteria in solid tumors (RECIST) and biological endpoints, e.g., tumor markers, may not always show a response and can be an unreliable guide to clinically relevant success [5]. However, the aim of the present work was a small pilot study to assess whether the designed endovascular RF catheter (VesCoag) could be used to negotiate the arterial blood supply of a primary or secondary cancer of the liver safely, then once deployed whether activation of the RF catheter would be tolerated by the patient and if the target vessel could be occluded by the endovascular use of RF energy. In all cases the RF catheter was manipulated into the target vessel but with the tortuous vessels, manipulation of the RF catheter did become more technically challenging and the stiffness of the probe was found to exacerbate this problem. Despite these issues, there were no cases of vessel dissection or rupture. Once correctly deployed the tip of the RF catheter had direct contact with the endothelium of the vessel and activation of the RF catheter was then able to deliver a high frequency alternating current to produce effective endovascular coagulation to obtain vessel occlusion. However, effective sealing of the target vessel with RF energy was only achieved in monopolar mode, only then was the generated heat sufficient to produce persistent closure of the vessel. A few patients did experience discomfort during the procedure but this was not found to correlate with when higher wattages were used and the one case where RF catheter activation was terminated because of pain, it was when it had been activated for the longest time period (Table 1). As this was a small pilot study where the newly designed RF catheter was used for the first time in patients, the objectives of the study were limited to the primary study endpoint of whether VesCoag could be manipulated into the target blood vessel and the secondary endpoint of whether on angiography the target vessel had been sealed by the use of RF energy. In the majority of cases, additional endovascular therapeutic maneuvers
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b b
Fig. 2: Intervention on a hepatocellular carcinoma in Segment VI, (a) deployment of VesCoag and angiogram prior to VesCoag activation, (b) completion of angiogram after VesCoag activation showing occlusion of the targeted vessel
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were performed such as chemoembolization, after endovascular delivery of RF energy (Table 1) so further detailed studies such as a randomized control trial are required to assess the true therapeutic benefit of VesCoag. Despite the limitations of the present study, the data obtained from the present pilot study is promising as it shows the device can be safely deployed and activated precisely in the target vessel, and when activated in monopolar mode, angiographic sealing of the vessel was achieved and tolerated by the patient. Therapeutic sealing of blood vessels is required in a number of clinical scenarios such as bleeding and cancer management, and the use of a RF catheter could be an alternative interventional radiology approach to the present strategy of embolization [8, 9] and further work is required to define and validate the role of the RF catheter against the established interventional radiology technique of embolization. But this work highlights that there is the opportunity and the need to continue to refine endovascular technology so that the outcome of transarterial therapies will continue to improve, by ensuring precise localization of treatment thereby minimising the morbidity and mortality that can arise.
Conflict of interest
Professor Nagy Habib declares a conflict of interest by being a shareholder and co-director in EMcision Ltd., London, UK.
References
[1] Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999;230:309–18. [2] Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol 1954;30:969–77. [3] Meric F, Patt YZ, Curley SA, et al. Surgery after downstaging of unresectable hepatic tumors with intra-arterial chemotherapy. Ann Surg Oncol 2000;7:490–5. ` [4] Camma C, Schepis F, Orlando A, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 2002;224:47–54. [5] Marelli L, Stigliano R, Triantos C, et al. Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 2007;30:6–25. [6] Takayasu K, Moriyama N, Muramatsu Y, et al. Gallbladder infarction after hepatic artery embolization. AJR 1985;144:135–8. [7] Khorsandi SE, Zacharoulis D, Vavra P, et al. The modern use of radiofrequency energy in surgery, endoscopy and interventional radiology. Eur Surg 2008;40:204–10. [8] Loewe C, Schindl M, Cejna M, et al. Permanent transarterial embolization of neuroendocrine metastases of the liver using cyanoacrylate and lipiodol: assessment of mid- and long-term results. AJR 2003;180:1379–84. [9] Sharma K, Gould JE, Harbour JW, et al. Hepatic arterial chemoembolization for management of metastatic melanoma. AJR 2008;190:99–104.
Acknowledgements
All RF catheters used in this study were provided free of charge by EMcision Ltd., London, UK.
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Initial data on a novel endovascular radiofrequency catheter