Electromagnetic thermal surgery system for liver resection: An animal study

Abstract

Purpose: Electromagnetic thermal surgery is a new technique. It applies an electrical current through coils to generate a high frequency magnetic field to heat up magnetic materials in the targeted area. Using this technique, we aim to perform liver resection without bleeding in rats and rabbits.

Materials and methods: The electromagnetic machine can produce a high frequency magnetic field, with an input of 220 V-55 A-60 Hz, an output frequency of 62.1 kHz, and a power of 2.2 kW. The magnetic materials used in this study were fine needles made of stainless steel. For ex vivo experiments, we used porcine liver explants; in the animal model, sixteen Sprague-Dawley rats and seven New Zealand White rabbits were used. We inserted one needle array along the attempted resection lines and then used the magnetic coils to heat up the needles for three min. After heating, we resected the designated liver portions using surgical scalpels.

Results: In the ex vivo test, the fine needles were heated up effectively to achieve tissue coagulation (more than 90°C). In the animal model the liver resection was performed without bleeding and no bile peritonitis was observed after the surgery. All animals were alive after the surgery until the end of the experiment (30 days).

Conclusions: The experiments showed that our thermal surgery system is very effective in performing bloodless liver resection without further ligation or embolisation needed. Our technique is new and the system has great potential to develop into clinical practice.

• electromagnetism
• liver resection
• thermal surgery
• thermo-coagulation

Introduction

Haemorrhage, bile leak, and hepatic failure are serious complications associated with liver resection. Techniques and devices that minimise these complications will be most helpful in the surgical management of liver disease. Over the years, different techniques have been developed to make liver resection easier and safer. Total blood loss can be reduced by occluding the vessels of the inflow (Pringle's manoeuvre) [1], the outflow, or both (total vascular exclusion). Although such vascular occlusion techniques are effective in controlling intraoperative bleeding, ischaemic reperfusion injury associated with the interruption of blood supply in hepatectomy is still a concern [2–4].

To perform bloodless liver resections without the need for vascular occlusion is therefore the aim of recent efforts in developing new devices for liver parenchyma resection [5–8]. Radiofrequency can generate heat by depositing energy through the electrode to the adjacent liver parenchyma by causing ionic vibration. Through heat, radiofrequency energy causes coagulative necrosis and vessel shrinkage in the liver resection margins, sealing off the blood vessels, which allows division of the parenchyma with a surgical scalpel [9].

In addition to radiofrequency ablation (RFA), heat can also be generated by magnetic particles or fluid [10], [11]. Similarly, when stainless steel needles (containing iron) are placed into a high-frequency alternating magnetic field generated by coils where a current passes through, an eddy current will be induced such that heat for tissue coagulation and effective haemostasis can be generated by Joule heating. The amount of heat energy generated depends on the power of the electro-magnetic field generator, the magnetic-sensitive objects (such as iron needles), and the position of the object in the magnetic field. All these parameters require verification and optimisation before we apply such electromagnetic thermal therapy for human liver resection. This article describes an innovative technique using electromagnetic thermal surgery to transect liver of rats and rabbits.

Materials and methods

Device for thermal surgery system

An alternating magnetic field was generated by a machine built in our laboratory, which has been described previously [12]. Briefly, the machine generates a high-frequency alternating magnetic field with an input of 220 V-55 A-60 Hz, an output frequency of 62.1 kHz, and a power of 2.2 kW at the centre of the induction coils, which are 75 mm in diameter (Figure 1). To facilitate operation the coil was made to be extended by using cables to connect it with the magnetic generator. The magnetic flux density 10 mm from the centre of the coils was about 2 T (measured by model 7030 Gauss/Tesla meter, F.W. Bell, Orlando, FL).

Figure 1. A schematic diagram of the electromagnetic thermal surgery system used in the study. The system was designed in our laboratory and custom-made by a commercial manufacturer.

Commercially available 30-gauge stainless-steel needles (Talihsin, Changhwa, Taiwan) were used for ex vivo porcine liver study (each 50 mm long, weighing 0.04 g) and in vivo animal studies (each 20 mm long, weighing 0.0106 g).

Ex vivo porcine liver and in vivo animal studies

Freshly isolated porcine liver was used to examine the thermal coagulation effect of our system. The temperature rise and the area of coagulative necrosis when using a single needle or a needle array (either a linear or a 3 × 3 layout) were measured by using an infrared imager (Infrared Thermography, TVS-200N, Nippon Avionics, Tokyo, Japan). Each test was repeated more than three times.

Sixteen male Sprague-Dawley rats (weighing 250–275 g) obtained from our university animal centre and 7 New Zealand white rabbits (weighing 3–3.5 kg) from the Live Stock Research Institute (Tainan, Taiwan) were used for studying the effect of electromagnetic thermoablation in living tissues with vivid blood flow. They were housed in a temperature and humidity controlled environment under a constant light cycle and had free access to water. This study protocol complied with the guidelines of the Helsinki declaration and was approved by the committee on laboratory animal research of our medical centre.

The animals were anaesthetised by intraperitoneal (rats) or intravenous (rabbits) administration of Zoletil 50 (Virbac, Carros, France) 0.1 mL/100 g in rats and 0.3–0.36 mL/kg in rabbits. The abdomens were shaved and disinfected with 10% povidone-iodine. Following a midline incision, the livers were exposed by retracting the abdominal wall aside. The needles were placed in a ‘W’ configuration with a 45° inclination and were inserted half-way into the liver. The inclination angle from parallel was 45°. With this layout we can use fewer needles (other than two parallel lines) to achieve a larger coagulating area. In our preliminary study, the effective distance of coagulative necrosis caused by a single needle was found to be about 5 mm which was re-confirmed by measuring the temperature in the ex vivo porcine liver study. Therefore, a 5-mm interval between needles was adopted in this study when a needle array was used. The livers then underwent a 3-min electromagnetic thermoablation. After the thermoablation, the liver parenchyma (including the gallbladders of rabbits) was transected along the coagulation line with a scalpel and the abdominal walls were closed in layers. The weights of removed liver parenchyma were recorded.

To observe the recovery process and complications of liver resection, animals were reared for further 30 days. On the day of sacrifice the animals were anaesthetised as described above in the Methods section. After examining the macroscopic findings, the remaining livers were promptly removed and processed for further histological examinations and the animals were sacrificed by anaesthesia overdose.

Histological examinations

To examine the immediate effect of electromagnetic thermoablation, about half of the liver immediately following transection was fixed in 10% formalin, sectioned, stained with haematoxylin-eosin and the other part was frozen in optimal cutting temperature compound by using liquid nitrogen to assess tissue viability with nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase staining. In brief, the frozen samples were sectioned, mounted on glass slides, and washed in water. The samples were then allowed to react for 20 min at room temperature with NADPH-diaphorase reaction solution (10 mL of 10 mmol/L PBS, pH 7.4, containing 10 mg NADPH, and 5 mg nitroblue tetrazolium).

The liver removed on the day of sacrifice was fixed in 10% formalin, sectioned, stained with haematoxylin-eosin and Masson-trichrome stain to examine the repair processes of the remnant of liver.

Results

Ex vivo porcine liver study

After a 3-min electromagnetic thermoablation, a single needle caused a raise of temperature up to 47° ± 1°C, whereas an array consisting of nine needles resulted in a temperature of 93° ± 2°C (Figures 2A and 2B). Such a temperature should be high enough to coagulate tissue, whereas a higher temperature may result in eschar formation and cause tissue to stick to the needle. We therefore determined the ablation period to be 3 min. The temperatures shown in Figure 2A were the ones measured at the needle tip when it was inserted in a porcine liver. The temperatures in between the needles were similar, as shown in Figure 2B when nine needles (3 × 3 array, with 5 mm separation distance) were inserted in a porcine liver. Since the needles were heated for 3 min, the temperature at the tip was very close to that in mid-needle since it is an excellent thermal conductive material. Using a needle array for thermoablation, the resection line showed a pale grey discoloration change as it had been completely coagulated (Figures 2C and 2D).

Figure 2. Ex vivo experiments: (A) and (B) temperature measurement by infrared imager. Note that in (A) a single needle was used, while in (B) nine needles were used; (B) produced a much higher temperature than (A). (C) An array of needles was inserted along the resection line over an isolated porcine liver with an interval of 5 mm between each other (arrow). (D) After a 3-min electromagnetic thermocoagulation, the cutting surface of the liver explant showed a completely ‘cooked’ appearance.

In vivo animal study

After a 3-min electromagnetic thermoablation the needle array created a 5 mm wide coagulation line which allowed transecting the livers of rats and rabbits without any significant blood loss (Figure 3). All the animals survived the operation and recovered uneventfully from the anaesthesia. The weight of resected liver was 1.2 ± 0.2 g for rats and 18 ± 1.8 g for rabbits.

Figure 3. Animal studies in rats (A-C) and rabbits (D-F). Note that needle arrays were aligned along the resection lines (A and D, arrows). After resection, the surfaces of remnant liver were completely coagulated and no bleeding was noted after the operation (B and E). Using electromagnetic thermal therapy, a part of the median lobe of liver was resected successfully (C and F).

All animals were alive 30 days after the liver resection. On opening the abdomen there was neither ascites formation nor bile leaked from the resection margin.

Histological examination

Microscopically, the resection margin of the immediately resected liver (Figures 4A–F) showed coagulative necrosis with loss of NADPH-diaphorase activity in the ablated area (Figures 4A and B: rat; 4D and E: rabbit).The blood vessels near the resection margin showed endothelial injury with intraluminal thrombus formation (Figure 4C: rabbit). Also, condensed plugs were also found in the lumen of adjacent bile duct (Figure 4F: rabbit). After 30 days of recovery a healing process was observed over the previously resected margin of the remnant liver which showed a fibrous band between the viable and necrotic tissues (Figures 4G–I: rabbit).

Figure 4. Histological examination of the immediately resected liver (A and B: rat; C-F: rabbit) and the remnant liver after a 30-day recovery (G-I: rabbit). The livers immediately after the resection showed coagulation necrosis with loss of NADPH-diaphorase activity in necrotic area (N) compared to viable liver tissue (V) (A, B, D and E). After the thermocoagulation, the lumen of blood vessel was blocked by thrombus (C, arrow) and the lumen of bile duct was blocked by condensed plugs (F, arrow). After a 30-day recovery, the resected margin of remnant liver showed a fibrous band (F) between viable liver tissue (V) and necrotic tissue (N) indicating a healing process (G-I). (A, D and G: H & E stain, 100×; C: H & E stain, 40×; F: H & E stain, 200×; B, E and H: NADPH-diaphorase stain, 100×; I: Masson-trichrome stain, 100×).

Discussion

Our study demonstrates that the heat generated by the electromagnetic thermal surgery system is sufficient to coagulate liver tissue, seal off the blood vessels and bile ducts to allow bloodless liver resection, and yet sacrificed minimal amount of normal tissue in small animals.The technique to apply our system is easy and the procedures take only a short time.

As instruments of thermal surgery, radiofrequency-assisted liver resections, such as Habib 4X [13], InLine [14] and Hexablate [15], can minimise blood loss and lower surgical morbidity particularly in cirrhotic livers. By sparing the use of vascular occlusion techniques, this technology as well as ours, can also avoid the complications associated with the ischaemia and reperfusion [16].

Biliary complications remain a main problem with radiofrequency assisted major liver resections, reported to range from 2.1% to 16% [17–18]. Our study showed that the bile ducts were sealed by condensed plugs immediately after thermoablation and secured by fibrotic tissue as noted after a 30-day follow up.

During the radiofrequency ablation, the tissue temperature has to be kept at or below 100°C because once the tissue temperature exceeds 100°C, intra- and extracellular water will boil, desiccating the tissue to form eschar, which is an electrical barrier to further coagulation. To control the temperature, radiofrequency probes require a sophisticated structure, therefore incurring higher cost. Although, we also kept the temperature around 95°C, eschar formation was not a concern of electromagnetic thermoablation, because the heat generated from the magnetic sensitive needle is controlled by a feedback system. In this way, the tissue will not become stuck to the needle and then pulled out with it. Furthermore, if the surface of needle is coated with Teflon, the modification can also prevent the needles from sticking to tissue effectively.

The electromagnetic thermocoagulation may have an advantage over radiofrequency ablation in that the magnetic sensitive needle is much cheaper than the radiofrequency probe, and, we can easily apply needles that are 10–50 mm long because inductive heat is the underlying working mechanism. Furthermore, second degree skin burns due to inadequate grounding surface or contact (3.7–10%) associated with radiofrequency ablation of hepatic tumour are reported [19]. Because no electricity passes through the body and no grounding pads are required for our method, such complications will be prevented. Judging from the efficiency of heat generation, our system can develop into percutaneous tools for thermoablation guided by imaging equipment.

We consider extended coil as a unique feature for our method that by controlling the distribution of the electromagnetic field, only the operative field will be locally heated. The present coil used covers a field of 75 mm diameter which would be able to transect human liver longitudinally in two sessions (i.e. in 6 min). What would be needed when translating our animal experiments to clinical use is a sterile plastic covering for wrapping the coil to prevent contamination of human tissue.

There are two limitations to our study. The first is that this new technique was just tested in small animals whose blood vessels were not large enough to generate the so called heat-sink effect seen in humans [20]. However, the histological character of human tissue should not be greatly different from that of rat or rabbit, as our electromagnetic system is able to raise the temperature constantly to around 100°C, we anticipate the vessels and bile ducts of humans should be coagulated as they were in the current rat and rabbit experiment. The efficiency of electromagnetic thermoablation on sealing the blood vessels and bile ducts will be confirmed in large animals. The second limitation is that the needle we used in this study is a prototype. Further improvements are required to facilitate its puncture into and removal from the liver.

Conclusion

In summary, our study has demonstrated a novel way to deliver heat by using electromagnetism to coagulate tissues for bloodless liver surgery; it is comparable with microwave or radiofrequency, and potentially can be even better. Our preliminary data provides a basis for further developments to facilitate bloodless liver resection clinically in the future.

Declaration of interest: This study was supported partly by a grant from the National Science Council of Taiwan, NSC 97-2627-B-006-007 and NSC 98-2627-B-006-003 and partly by a grant from Industry Technology Research Institute ITRI 2009-08569. Roberto Zuchini, a physician and PhD student, was supported by an international scholarship from National Cheng Kung University. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.