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AMICA Apparatus for MICrowave and radiofrequency Ablation THE NEW GENERATION OF INTERSTITIAL PROBES FOR MICROWAVE AND RADIOFREQUENCY THERMOABLATION

THE NEW GENERATION OF INTERSTITIAL PROBES FOR … Cat 2018 elektronisk udgave.… · • RF ablation is now widely used in the treatment of hepatocellular carcinoma (HCC) with a diameter

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Page 1: THE NEW GENERATION OF INTERSTITIAL PROBES FOR … Cat 2018 elektronisk udgave.… · • RF ablation is now widely used in the treatment of hepatocellular carcinoma (HCC) with a diameter

AMICA Apparatus for MICrowave

and radiofrequency Ablation

THE NEW GENERATION OF INTERSTITIALPROBES FOR MICROWAVE AND

RADIOFREQUENCY THERMOABLATION

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AMICA GEN

2

AMICA GEN is a programmable microwave (MW, 2450 MHz) and radiofrequency (RF, 450 kHz) generator, the only available generator capable of providing the two most widespread thermoablation technologies in the same hardware.

AMICA is the only system in the world that combines the two main thermal ablation technologies, radiofrequency (RFA) and microwave (MWA), in the same hardware.

INTRODUCTION TO THERMAL ABLATION

The ablation of a biological tissue consists in destroying it with a physical or chemical agent capable of killing it's cells. In particular, thermal ablation is the coagulation necrosis induced in a mass of tissue by the effect of local overheating: cell death is practically instantaneous at temperatures of 60°C or more.

Ablation is currently used in clinical practice for destroying pathological tissues (for example, tumors or hypertrophic masses) in cases in which surgical resection is not practicable or contraindicated: hence the prevalence of interstitial or intracavitary ablation applicators, which are minimally invasive.

The pathological tissues most frequently subjected to ablation are solid tumors. The incidence of cancer increases with the age of individuals whilst the capacity to withstand surgical operations decreases.

The increase in the average age of the population thus causes an ever-increasing demand for local and regional treatments less invasive than traditional surgery.

In addition, compared to surgical resection, an interstitial ablation operation has shorter times and lower costs and risks before, during and after the operation, above all due to the significant reduction in invasiveness and the trauma suffered by the patient, the consequent reduction in the complication rate and side effects and the shortening of the post- operative course.

CE approved

References - please look at page 10 & 11

Manufactured by: HS HOSPITAL SERVICE S.P.A.

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FUNDAMENTAL REQUIREMENTS OF A THERMAL ABLATION SYSTEM

At present, heating from electromagnetic energy sources satisfies the most diverse needs better than any other ablation system (cryoablation, percutaneous ethanol injection (PEI), irreversible electroporation, “TACE” transarterial chemoembolization, ”HIFU” high-intensity focused ultrasound, etc.):

Control of necrosis pattern

• Predictability of the therapeutic outcome (shape and size of the ablated volume) under assigned operating conditions (type of target tissue, type and dose of energy administered, method and duration of energy output)

• Minimum and maximum coagulation performance (shapability of thermal lesion)• Confinement (sphericity, preservation of tissues around the target, lack of interference with

implanted medical devices and prostheses)Heating speed

• Short duration of treatment• Low sensitivity to heat sinking effects due to blood circulation or bile ductsSafety

• Minimal invasiveness, low intra- and post- operative complication rate, EMC compatibility and electrical safety, availability of alarms and hardware and software protective devices

Ease of use

• Short learning curve, full compatibility with the principal imaging techniques, easy access to the tumor, real-time control of the progress of treatment

Accessible costs

• It is therefore no surprise that the ablation techniques most commonly used today are radiofrequency thermal ablation (RFA) and microwave thermal ablation (MWA)

RADIOFREQUENCY THERMAL ABLATION (RFA)

• Radiofrequency (RF) consists of alternating electric currents at radio frequencies (typically around 450 kHz) that heat the tissues through the Joule effect and ionic agitation (the heat produced is directly proportional to the current density)

• RF applicators are thin interstitial electrodes (between 14G and 20G), capable of penetrating into the lesion to be subjected to ablation, where they inject RF currents of a suitably adjustable intensity. The electrical circuit is closed by special dispersion plates applied to the patient’s skin

• RF currents only heat the tissue near the exposed tip of the electrode: propagation of the heat takes place more slowly by thermal conduction

• RF technology is a reliable and economical method of generating, controlling and supplying energy to the tissues safely and effectively with low complication rates

• RF ablation is now widely used in the treatment of hepatocellular carcinoma (HCC) with a diameter of up to 3 cm and, to a lesser degree, lung cancer, osteoid osteoma and bone metastases; less systematically, there are reports in the literature of RF treatments on kidney, prostate and breast tumors.

MICROWAVE THERMAL ABLATION (MWA)

• Microwaves are electromagnetic radiation with a frequency of between 300 MHz and 300 GHz that induces atomic and molecular dipole rotation, creating a kind of friction that converts part of the energy of the field applied into heat (dielectric heating)

• This form of heating is particularly efficient in materials with high water content, like most biological tissues

• A microwave applicator may deposit radiant energy inside the human body in a localized and controlled way, irrespective of the electrical properties of the tissue and without any need for dispersion plates

MW Field Dipoles Oscillations

References - please look at page 10 & 11

Manufactured by: HS HOSPITAL SERVICE S.P.A.

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AMICA GEN AGN-H-1.2

4

Automatic identification of the type of applicator (RF or MW ), the model (gauge, length and exposure) and automatic selection of the corresponding type of energy to be supplied Automatic identification of the energy output mode (AUTO, MAN, TEMP) and auto setting of the default parameters Automatic control peristaltic pump built into the generator for internal cooling of both types of applicator Essential and user-friendly graphic inter face: LCD touch screen and rotary knob for browsing through the setup menus Possibility of adjusting the power output (MW and RF) during both the setup and the treatment phases Storage of data and settings from the latest ablation session

Product

References - please look at page 10 & 11

Self-diagnosis of applied parts status and of MW and RF amplifiers1 Automatic shut-off of energy output in case of an alarm or error Acoustic and visual warning of the alarm state, of the correct connection and functioning of the applied parts Constant monitoring of the energy output: continuous measurement of direct and reflected MW power; continuous measurement of power, current and RF impedance Calculation of net MW and RF energy deposited in the tissues Local or remote control of energy output (MW and RF) Direct energy output emergency stop button

Safety Charateristics

AMICA GEN AGN-H-1.2 is a programmable solid-state generator that can output, control and release

radiofrequency power (RF, at 450 kHz) and microwave power (MW, at 2450 MHz).

Microwave (2450 MHz /190 W) and radiofrequency (450 kHz /200 W on 50 Ω load) dual generator Two different MW energy delivery modes: MAN (continuous power delivery) and PULSED (intermittent power delivery [40]) Three radiofrequency energy output modes: AUTO (power regulated automatically according to impedance), MAN (preset power output) and TEMP (power regulated automatically according to the temperature set) Equipped with an automatic procedure for cauterizing the applicator entry path at the end of treatment (track ablation) Built-in AMICA-PUMP peristaltic pump LCD touch screen and rotary knob Connectivity: AMICA GEN is interfaceable with a PC or other external devices by specific serial communication port (RS 232) Service output (30 VDC /100 mA) for powering external devices Maximum portability and compactness: the lightest (12 kg) and smallest (45x38x13 cm) thermal ablation device in the world

Technical Charateristics

Manufactured by: HS HOSPITAL SERVICE S.P.A.

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Item no. Specification

AGN-3.22450MHz/190W programmable solid-state MW generator, with built-in peristaltic pump

AGN-H-1.2Programmable RF (450kHz/200W @ 50 Ohm) and MW (2450MHz/190W) generator, with built-in peristaltic pump

AGN-R-1.1Programmable RF generator (450kHz/200W@50Ohm) with built-in peristaltic pump

AMICA Programmable RF & MW generators

BENEFITS OF LOCO-REGIONAL TREATMENTS• minimally invasive, precise, simple to use, safe and inexpensive [1], [15]• may be per formed via the percutaneous or laparoscopic route or even in an intraoperative setting• compatible with the principal imaging techniques (US, CT, MRI) [2],[7]• may be performed under general anaesthesia or deep sedation. Sometimes a local anaesthetic and

mild sedation are sufficient• well tolerated by patients and widely applicable [3]• short sessions and rapid post-operative course• immediate therapeutic effect• low complication rate [4]• may be performed in the operating theatre, but also in the CT room or an outpatient

department [5]• reduction of costs for healthcare facilities

BENEFITS OF RFA• regular and repeatable ablation volume [16]• proven efficacy in the treatment of hepatocellular carcinoma (HCC) with a diameter of

up to 3 cm [6]• real-time display of the development of the coagulation zone

BENEFITS OF MWA• repeatability, uniformity and homogeneity of the ablation volume (no skipping) [8], [9], [14]• larger ablation volume [10], [11], [21]• accurate real-time display of the development of the coagulation zone• rapid heating of the tissue subjected to treatment (much less sensitive to heat sinking) [8]• possibility of treating a vast range of tissues (fatty, spongy and irregular tissues, bone

tissues and muscle fibres) such as: liver, lung, kidneys, bone, breast, etc. [10], [11], [12]• possibility of treating patients with implanted metal devices (pacemaker, prosthesis, clip, stent, etc.)

The HS AMICA hybrid system, which combines the RF and MW technologies in a single generator, allows the operator to choose the most suitable technology according to:• the morphological and histological characteristics of the

tumor to be treated• the type of tissue to be treated• the presence of structures beside the tumor

(e.g. vessels, colon, etc.)• the expected cost-benefit ratio

References - please look at page 10 & 11

Manufactured by: HS HOSPITAL SERVICE S.P.A.

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AMICA PROBE MW

AMICA PROBE is a single-use interstitial applicator for percutaneous or intraoperative use for the microwave thermal ablation of soft tissues.

Ablation up to a transverse diameter of 5.7 cm in 15 minutes at 100W1 [23], [34] More spherical ablation up to 4.5 cm transversal diameter3 Full control of the necrotic area, maximum repeatability and safety of treatment due to the combined action of the patented mini- choke2 (which eliminates the effects of retrograde heating) device and the cooling inside the applicator [22], [23], [24] Size and sphericity index adjustable by varying the duration and power of ablation [34] Clinical efficacy and safety of use demonstrated on a wide range of tissues [21], [26], [27], [28], [29], [30], [31], [32], [35] Better ratio between available gauge and sphericity index than all other microwave applicators on the market

AMICA PROBE MW • PERFORMANCE

Medical grade stainless steel cannula with depth markers. A large white band extending between 3 cm and 4 cm from the tip improves control during the track ablation by pointing out the proximity of the antenna to the skin Pyramidal metal tip to facilitate tissue penetration Excellent visibility under US and CT guidance Integrated memory chip for identifying the applicator and recording the factory settings Internal temperature sensor for measuring the temperature of the applicator probe Built-in or separable hydraulic line and coaxial power cable (identified by the suffix -DC) Multiple use per patient Possibility of using multiple applicators at the same time [10] No dispersion plates applied to the patient

AMICA PROBE MW • TECHNICAL CHARACTERISTICS

The disposable kit that comes with the device comprises:

• Polyethylene removable guard assembled above the probe of the applicator

• Insertion depth indicator• Disposable scalpel for preliminary cutting of the patient’s skin• Operating drape with hole at the centre• Applicator with sponge for disinfecting the patient’s skin• Cable holder/fixator

References - please look at page 10 & 11

Manufactured by: HS HOSPITAL SERVICE S.P.A.

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COAGULATIVE PERFORMANCE OF AMICA PROBE IN EX-VIVO LIVER

(Pulsed Mode) [40]

COAGULATIVE PERFORMANCE OF AMICA PROBE IN EX-VIVO BOVINE LIVER

(Continuous Mode)

POWER⁷ TIME11 SIZE(Length x Diameter)10 SPHERICIT INDEX (D/L)

20W 10 MIN 22x22 1.00

40W 5 MIN 29x25 0.86

70W 10 MIN 36x33 0.92

100W12 10 MIN 42x36 0.86

120W12 10 MIN 51x41 0.80

140W13 10 MIN 53x46 0.87

Item no. Model Description

APK11150T19V5⁴,⁵ 11Gx150mm Gauge 11G, length 150mm

APK14150T19V5⁴,⁵ 14Gx150mm Gauge 14G, length 150mm

APK14200T19V5⁴,⁵ 14Gx200mm Gauge 14G, length 200mm

APK14270T19V5⁴ 14Gx270mm Gauge 14G, length 270mm

APK16150T19V5⁵ 16Gx150mm Gauge 16G, length 150mm

APK16200T19V5⁵ 16Gx200mm Gauge 16G, length 200mm

APK16270T19V5 16Gx270mm Gauge 16G, length 270mm

AMICA Disposable Microwave Ablation Probes

Available versions:gauge: 11G, 14G, 16G

shaft length: 150, 200, 270 mmbuilt-in or detachable cableshigh power version (100W)

SIZE(Length x Diameter)⁶

POWER⁷

20W 40W 60W 80W 100W⁹

TIME⁸

3 MIN 24 x 16 29 x 20 37 x 25 46 x 32 52 x 36

5 MIN 27 x 20 36 x 28 48 x 34 52 x 37 57 x 38

10 MIN 31 x 27 49 x 36 54 x 40 66 x 46 71 x 48

15 MIN 38 x 33 50 x 42 61 x 48 73 x 55 80 x 57

References - please look at page 10 & 11

Manufactured by: HS HOSPITAL SERVICE S.P.A.

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AMICA PROBE RF

RF AMICA PROBE is a single-use interstitial electrode for percutaneous or intraoperative use for the rodiofre quency thermal ablation of soft tissues.

Coagulation up to a transverse diameter of 3.5 cm in 12 minutes at 200W in AUTO output mode1⁴ Maximum coagulation performance obtained through automatic control of the power output (AUTO mode) and internal cooling that prevents carbonization of the tissues around the exposed tip

AMICA PROBE RF • PERFORMANCE

Power available at the RF AMICA-PROBE radiofrequency electrode: up to 200W with an impedance of 50 Ω measured between the electrode and the dispersion plates Excellent visibility under US and CT guidance Trocar pyramidal tip to facilitate tissue penetration without skin incision Integrated memory chip for identifying the applicator and recording the factory settings Internally cooled straight monopolar electrode Temperature sensor beside the tip of the electrode for measuring cooling efficiency Medical grade stainless steel cannula with depth markers Built-in hydraulic line and power cable Multiple use per patient

AMICA PROBE RF • TECHNICAL CHARACTERISTICS

Probe models already available:gauge: 17G & 18G

shaft length: 100, 150, 200, 270 mmexposed tip length:

5, 10, 15, 20, 25, 30, 35 mm

References - please look at page 10 & 11

Manufactured by: HS HOSPITAL SERVICE S.P.A.

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GENERAL USE [6] [36] (Liver - Lung Uterine Fibroid Bone Metastasis Kidney, Etc)

Item no. Specification Item no. Specification

RFH17100E05V1 17G x 100 mm, 5 mm exposed tip RFH17150E30V1 17G x 150 mm, 30 mm exposed tip

RFH17100E07V1 17G x 100 mm, 7 mm exposed tip RFH17150E35V1 17G x 150 mm, 35 mm exposed tip

RFH17100E10V1 17G x 100 mm, 10 mm exposed tip RFH17200E10V1 17G x 200 mm, 10 mm exposed tip

RFH17100E20V1 17G x 100 mm, 20 mm exposed tip RFH17200E20V1 17G x 200 mm, 20 mm exposed tip

RFH17100E30V1 17G x 100 mm, 30 mm exposed tip RFH17200E25V1 17G x 200 mm, 25 mm exposed tip

RFH17150E10V1 17G x 150 mm, 10 mm exposed tip RFH17200E30V1 17G x 200 mm, 30 mm exposed tip

RFH17150E20V1 17G x 150 mm, 20 mm exposed tip RFH17200E35V1 17G x 200 mm, 35 mm exposed tip

RFH17150E25V1 17G x 150 mm, 25 mm exposed tip

THYROID GLAND [37] [38] OSTEOID OSTEOMA [20]

Item no. Specification Item no. Specification

RFH18070E05V1-T1⁵ 18G x 70 mm, 5 mm exposed tip RFH17100E05V1-0S 17G x 100 mm, 5 mm exposed tip

RFH18070E07V1-T1⁵ 18G x 70 mm, 7 mm exposed tip RFH17100E07V1-0S 17G x 100 mm, 7 mm exposed tip

RFH18070E10V1-T1⁵ 18G x 70 mm, 10 mm exposed tip RFH17100E10V1-0S 17G x 100 mm, 10 mm exposed tip

RFH18070E15V1-T1⁵ 18G x 70 mm, 15 mm exposed tip RFH17100E15V1-0S 17G x 100 mm, 15 mm exposed tip

RFH18100E05V1-T1⁵ 18G x 100 mm, 5 mm exposed tip RFH17150E05V1-0S 17G x 150 mm, 5 mm exposed tip

RFH18100E07V1-T1⁵ 18G x 100 mm, 7 mm exposed tip RFH17150E07V1-0S 17G x 150 mm, 7 mm exposed tip

RFH18100E10V1-T1⁵ 18G x 100 mm, 10 mm exposed tip RFH17150E10V1-0S 17G x 150 mm, 10 mm exposed tip

RFH18100E15V1-T1⁵ 18G x 100 mm, 15 mm exposed tip RFH17150E15V1-0S 17G x 150 mm, 15 mm exposed tip

LAPAROSCOPIC PROCEDURE [31]

RFH17250E30V1 17G x 250 mm, 30 mm exposed tip

RFH17270E20V1 17G x 270 mm, 20 mm exposed tip

RFH17270E25V1 17G x 270 mm, 25 mm exposed tip

RFH17270E30V1 17G x 270 mm, 30 mm exposed tip

RFH17270E35V1 17G x 270 mm, 35 mm exposed tip

AVAILABLE MODELS • RF AMICA-PROBE

COAGULATION PERFORMANCE OF RF AMICA-PROBE ON BOVINE LIVER

Ablation size (Length x Diameter)

Automatic enery delivery mode 200W max, 10 minutes

Length of exposed tip (mm)

10 mm 20 mm 30 mm

13 x 11 30 x 22 41 x 33

References - please look at page 10 & 11

Manufactured by: HS HOSPITAL SERVICE S.P.A.

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AMICA GEN • AMICA PROBE MW • AMICA PROBE RFReferences:1. From ex vivo tests on bovine liver at room temperature.2. World patent of the Italian National Research Council (CNR), on an exclusive licence to HS3. From ex-vivo tests on bovine liver at room temperature in pulsed mod energy deliver y4. For the high-power version with a short coaxial cable (1.5m), add the following suffix to the code: –S1.55. For the version with detachable cables, add the following suffix to the code: –DC6. Size of necrosis obtained from the mean of three repetitions on adult bovine liver, initially at room temperature (~20°C): all sizes were obtained

using a single applicator and single insertion. The in-vivo sizes of coagulation necrosis could vary (a diameter of -10% and a length of -20% are estimated) due to blood per fusion)

7. Net power in the radiant part of the applicator8. Continuous energy output9. Only with 1.5 m coaxial cable (-S1.5)10. Per formance char t applicable to 14G AMICA-PROBE models only, cooled using pre -refrigerated water (≤10°C). Size of necrosis obtained from the

mean of three repetitions in ex-vivo bovine liver, initially at room temperature (~20°C): all sizes were obtained using a single applicator and single inser tion. The in vivo sizes of the coagulation necrosis could change (-10% in diameter and -20% in length) due to blood per fusion

11. Pulsed energy deliver y mode. Pulse width (tON): 4 sec; Latency (tOFF): 6 sec12. Only achievable with AMICA-GEN units featuring a 190W microwave amplifier on board13. Only achievable with AMICA-GEN units featuring a 190W microwave amplifier on board and with the detachable applicator model only (add the

-S1.5 suffix to the code)14. From ex-vivo test on bovine liver at room temperature15. For the version with straight handle, replace V1 with V216. Size of necrosis obtained from the mean of three repetitions on adult bovine liver, initially at room temperature (~20°C): all sizes were obtained

using a single applicator and a single insertion. The size of the in-vivo coagulation necrosis could vary due to blood per fusion.17. Available AGN unit featuring a 190w microwave amplifier on board

References:[1] Gerald D. Dodd III, Michael C. Soulen, Rober A. Kane, Tito Livraghi, William R. Lees, Yasuyuki Yamashita, Alison R. Gillams, Okkes I. Karahan, Hyunchul Rhim. “Minimally Invasive Treatment of Malignant Hepatic Tumors: At the Threshold of a major breakthrough ”. Radiographics 2000; 20:9-27[2 ]Eric Van Sonnenberg, M.D., William McMullen, Luigi Solbiati. “Tumor Ablation: Principles and Practice”. Book: Springer, 13/jul/2005[3] Muneeb Ahmed, Christopher L. Brace, Fred T. Lee, Jr, S. Nahum Goldberg “Principles of and advances in Percutaneous Ablation”. Radiology: Volume 258: Number 2, February 2011[4] L. C. Bertot, M. Sato, R. Tateishi, H. Yoshida, K. Koike; “Mortality and complication rates of percutaneous ablative techniques for the treatment of liver tumors: a systematic review ” Eur Radiol. 21 2584 (2011) [5] Matthew R., Callstrom and J. William Charboneau. “Technologies for Ablation of Hepatocellular Carcinoma”. Gastroenterology 2008; 134:1831–1841[6] N'Kontchou G, Mahamoudi A, Aout M, Ganne-Carrié N, Grando V, Coderc E, Vicaut E, Trinchet JC, Sellier N, Beaugrand M, Seror O. “Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis”. Hepatology. 2009 Nov; 50(5):1475-83. doi: 10.1002/hep.23181[7] Ann P O’Rourke, dieter Haemmerich, Punit Prakash, Mark C Converse, David M Mahvi and John G Webster. “Current status of liver tumor ablation devices”. Future Drugs Ltd 2007[8] Bhardwaj N, Strickland AD, Ahmad F, Atanesyan L, West K, Lloyd DM. “A comparative histological evaluation of the ablations produced by microwave, cryotherapy and radiofrequency in the liver” Pathology. 2009 Feb; 41(2):168-72.[9] Gianpiero Gravante, Seok L. Ong, Matthew S. Metcalfe, Andrew Strickland, Ashley R. Dennison and David M. Lloyd. “Hepatic microwave ablation: a review of the histological changes following thermal damage”. Liver International ISSN 1478-3223[10] Meghan G. Lubner, MD, Christopher L. Brace, PhD, J. Louis Hinshaw, MD, and Fred T. Lee, Jr, MD. “Microwave Tumor Ablation: Mechanism of Action, Clinical Results, and Devices”. J Vasc Interv Radiol 2010; 21:S192–S203 [11] JING ZHANG, LEI FENG, BINGSONG ZHANG, JINTAO REN, ZHENCAI LI, DONGMEI HU, & XUE JIANG. “Ultrasound-guided percutaneous microwave ablation for symptomatic uterine fibroid treatment – A clinical study”. Int. J. Hyperthermia, August 2011; 27(5): 510–516[12] Wenbin Zhou, Xiaoming Zha, Xiaoan Liu, Qiang Ding, Ling Chen, Yicheng Ni, Yifen Zhang, Yi Xu, Lin Chen, Yi Zhao, Shui Wang. “US-guided Percutaneous Microwave Coagulation of Small Breast Cancers: A Clinical Study”. Radiology: Volume 263: Number 2—May 2012[13] A. Andreano, Yu Huang, M. F. Meloni, Fred T. Lee, Jr., Christopher Brace. “Microwaves create larger ablations than radiofrequency when controlled for power in ex vivo tissue”. Med Phys. 2010 June; 37(6): 2967–2973. [14] Strickland AD, Clegg PJ, Cronin NJ, Swift B, Festing M, West KP, Robertson GS, Lloyd DM. Experimental study of large-volume microwave ablation in the liver. Br J Surg. 2002 Aug; 89(8):1003-7.[15] Awad MM, Devgan L, Kamel IR, Torbensen M, Choti MA. “Microwave ablation in a hepatic porcine model: correlation of CT and histopathologic findings”. HPB (Oxford). 2007; 9(5):357-62.[16] Ong SL, Gravante G, Metcalfe MS, Strickland AD, Dennison AR, Lloyd DM. “Efficacy and safety of microwave ablation for primary and secondary liver malignancies: a systematic review”. Eur J Gastroenterol Hepatol. 2009 Jun;21(6):599-605.

Manufactured by: HS HOSPITAL SERVICE S.P.A.

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References cont.:[17] S. Nahum Goldberg. “Radiofrequency tumor ablation: principles and techniques”. Eur J Ultrasound 2001 Jun; 13(2):129-147[18] W.K. Jeong, J.H. Baek, H. Rhim, Y.S. Kim, M. S. Kwak, D. Lee; “Radiofrequency ablation of benign thyroid nodules: safety and imaging follow up in 236 patients” Eur Radiol 18: 1244-1250 (2008).[19] J. H. Baek, J. H. Lee, J.Y Sung, Jae-Ik Bae, K. T. Kim,J. H. Shin, etc; “Complications Encountered in the Treatment of Benign Thyroid Nodules with US-guided Radiofrequency Ablation: A Multicenter Study” Radiology 262 1(2012). [20] Daniel I. Rosenthal, MD, F. J. Hornicek, MD, PhD, M. Torriani, MD, Mark C. Gebhardt, MD and Henry J. Mankin, MD. Osteoid Osteoma: “Percutaneous Treatment with Radiofrequency Energy” Radiology 2003; 229:171–175 [21] G Poggi, B Montagna, P Di Cesare, G Riva, G Bernardo, M Mazzucco, A Riccardi. “Microwave Ablation of Hepatocellular Carcinoma using a New Percutaneous Device: Preliminary Results”. Anticancer Res. 2013 Mar; 33(3):1221-1227.[22] I.Longo, G. Biffi Gentili, M.Cerretelli, N.Tosoratti; “A Coaxial Antenna With Miniaturized Choke for Minimally Invasive Interstitial Heating”, IEEE Trans. on Biomed. Eng., 50 82 2003[23] M. Cavagnaro, C. Amabile , P. Bernardi, S. Pisa, N. Tosoratti; “A Minimally Invasive Antenna for Microwave Ablation Therapies: Design, Performances, and Experimental Assessment”, IEEE Trans. on Biomed. Eng. 58 949 2011 [24] Riccardo Bartoletti, Tommaso Cai, Galliano Tinacci, Iginio Longo, Andrea Ricci, Maria Pia Massaro, Nevio Tosoratti, Enzo Zini and Novello Pinzi "Transperineal Microwave Thermoablation in Patients with Obstructive Benign Prostatic Hyperplasia: A Phase I Clinical Study with a New Mini-Choked Microwave Applicator” JOURNAL OF ENDOUROLOGY VOL. 22, NO. 7, JULY 2008[25] Riccardo Bartoletti, Tommaso Cai, Nevio Tosoratti, Claudio Amabile, Alfonso Crisci, Galliano Tinacci, Nicola Mondaini, Paolo Gontero, Sandro Gelsomino and Gabriella Nesi. "In vivo microwave-induced porcine kidney thermoablation: results and perspectives from a pilot study of a new probe” (JOURNAL COMPILATION BJU INTERNATIONAL, NOVEMBER 2009).[26] Riccardo Bar toletti, Enrico Meliani, Alchiede Simonato, Paolo Gontero, Giovanna Ber ta, Paolo dalla Palma, Elena Leonardi, Tommaso Cai and Giorgio Carmignani. “Microwave-induced thermoablation with Amica-probe is a safe and reproducible method to treat solid renal masses: Results from a phase I study”. ONCOLOGY REPORTS, JUNE 2012.[27] Olivier Planché, Christophe Teriitehau, Sana Boudabous, Joey Marie Robinson, Pramod Rao, Frederic Deschamps, Geoffroy Farouil, Thierry De Baere. “In Vivo Evaluation of Lung Microwave Ablation in a Porcine Tumor Mimic Model”. CARDIOVASC INTERVENT RADIOL, APRIL 2012[28] Claudio Pusceddu, Barbara Sotgia, Rosa Maria Fele and Luca Melis. “Treatment of Bone Metastases with Microwave Thermal Ablation”. (J VASC INTERV RADIOL, VOL. 24, NO. 2, FEBRUARY 2013).[29] Microwave Thermal Ablation for Hepatocarcinoma: Six Liver Transplantation Cases. G. Zanus, R. Boetto, E. Gringeri, A. Vitale, F. D’Amico, A. Carraro, D. Bassi, P. Bonsignore, G. Noaro, C. Mescoli, M. Rugge, P. Angeli, M. Senzolo, P. Burra, P. Feltracco and U. CIllo (TRANSPLANTATION PROCEEDINGS, VOL. 43, FEBRUARY 2011).[30] O. M. Hetta, N. H. Shebrya, S. K. Amin. “Ultrasound-guided microwave ablation of hepatocellular carcinoma: Initial institutional experience”. (THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE, AUGUST 2011). [31] Umberto Cillo, Alessandro Vitale, Davide Dupuis, Stefano Corso, Daniele Neri, Francesco D’Amico, Enrico Gringeri, Fabio Farinati, Valter Vincenzi, Giacomo Zanus. “Laparoscopic Ablation of Hepatocellular Carcinoma in Cirrhotic Patients Unsuitable for Liver Resection or Percutaneous Treatment: A Cohort Study” (PLOS ONE, VOL. 8, FEBRUARY 2013).[32] Tito Livraghi, Franca Meloni, Luigi Solbiati, Giorgio Zanus. “Complications of Microwave Ablation for Liver Tumors: Results of a Multicenter Study”. (CARDIOVASC INTERVENT RADIOL, AUGUST 2011).[33] Maria Franca Meloni, Anita Adreano, Giorgio Bovo, Bartolomeo Chiarpotto, Claudio Amabile, Sandro Gelsomino, Sergio Lazzaroni and Sandro Sironi. "Acute Portal Venous Injury after Microwave Ablation in an in Vivo Porcine Model: A Rare Possible Complication”. (J VASC INTERV RADIOL, VOL. 22, NO. 7, JULY 2011).[34] Rudiger Hoffmann, Hansjorg Rempp, Ludwig Enhard, Gunnar Blumenstock, Philippe L. Pereira, Claus D. Claussen and Stephan Clasen. “Comparison of Four Microwave Ablation Devices: An Experimental Study in ex Vivo Bovine Liver”. (RADIOLOGY RSNA, FEBRUARY 2013).[35] Paola Tombesi, Francesca Di Vece, Sergio Sartori. “Resection vs thermal ablation of small hepatocellular carcinoma: What's the first choice?”. World J Radiol 2013 January 28; 5(1): 1-4[36] Ashraf Abdelaziz, Tamer Elbaz, Hend Ibrahim Shousha, Sherif Mahmoud, Mostafa Ibrahim, Ahmed Abdelmaksoud, Mohamed Nabeel “Efficacy and survival analysis of percutaneous radiofrequency versus microwave ablation for hepatocellular carcinoma: an egyptian multidisciplinary clinic experience”Surg Endosc 14 May 2014 Surg Endosc DOI 10.1007/s00464-014-3617-4 [37] Stella Bernardi, Chiara Dobrinja, Bruno Fabris, Gabriele Bazzocchi, Nicoletta Sabato, Veronica Ulcigrai, Massimo Giacca, Enrica Barro, Nicolò De Manzini, and Fulvio Stacul “Radiofrequency Ablation Compared to Surgery for the Treatment of Benign Thyroid Nodules” International Journal of Endocrinology Volume 2014, Article ID 934595, 10 pages http://dx.doi.org/10.1155/2014/934595[38] Chiara Dobrinja, Stella Bernardi, Bruno Fabris, Rita Eramo, PetraMakovac, Gabriele Bazzocchi, Ganfranco Piscopello, Enrica Barro, Nicolò de Manzini, Deborah Bonazza, Maurizio Pinamonti, Fabrizio Zanconati, and Fulvio Stacul “Surgical and Pathological Changes after Radiofrequency Ablation of Thyroid Nodules” International Journal of Endocrinology Volume 2015, Article ID 576576, 8 pages http://dx.doi. or- g/10.1155/2015/576576[39] Claudio Pusceddu, Barbara Sotgia, Rosa Maria Fele, Nicola Ballicu, Luca Melis “Combined Microwave Ablation and Cementoplasty in Patients with Painful Bone Metastases at High Risk of Fracture “ Cardiovasc Intervent Radiol 26 May 2015 DOI 10.1007/s00270-015-1151-y[40] Pulsed Microwave Ablation: A multi-parametric study in ex-vivo bovine liver. C. Amabile, Ph.D.; S. Cassarino; N. Tosoratti. Ph.D - R&D HS Hospital Service SPA Roma, Italy

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