RFA (radiofrequency ablation) is a minimally invasive treatment techniques which creating thermally to turn tumor into coagulation necrosis. There are mainly two methods, one is guidance by imaging technology such as ultrasound, CT, MR imaging etc. with percutaneous approach. Another is using the electrodes to insert into tissues by surgeons. RF ablation is widely used in hepatocellular carcinoma, kidney cancer, lung cancer and bone cancer etc. This paper is focus on the kinds of electrodes or probes with their principles and functions.
How radiofrequency (RF) works
The frequency transmitter generates high radio frequency AC current which though the electrode needle into the tumor tissue via non-conduction probes. This current in the electrode will generate the electromagnetic field around the contacted tissue. Obviously, the ions in tumor tissue will frequent oscillates as the electric field, which is proportional to the RF intensity. Biological macromolecules with the polarity of the current will transform and frequent changes in direction of polarization. The tumor tissue temperature will rise by the ways described prior which transform the electrical energy into heat via friction.
The coagulation necrosis caused by RF ablation depend both the tissue temperature rise and the lasting time of the heating. Cellular homeostasis could able to maintain normal function in the temperature to about 40°C. When the ambient temperature rises to 42 ~ 45°C, cells become more sensitive so that easy to damage by other factors such as chemotherapy, radiation etc. However, cells cannot be completely killed in a given tissue at this temperature, proliferation of the tumor will continue for a period of time. When temperature rises to 46~60°C[1], the cells suffer from the fatal damage in a very short time. Between the 60~100°C[2], almost immediately lead to protein coagulation, the cytoplasmic enzyme structure, enzyme structure of mitochondrial and nuclear DNA groups within the protein complex by irreversible damage. The temperature higher than 105°C[3], could cause tissue carbonization or even more serious unrecoverable injury. Tumor tissue has a special sensitivity to heat. Because microcirculation of tumor vessels and structures are hypogenetic compared with normal tissues, so that blood flow within the tumor is slow, about 10% of the normal tissue around, which leading to lower heat dissipation, heat accumulation in tumor tissue is easy. The temperature of tumor tissue is 5~10°C higher than normal tissue with receiving the same dose of heat. The percentage of hypoxic cells in animal tumor is 10%~20%. However the proportion of hypoxic cells in human tumor is far higher than the percentage which in animals'. Hypoxic cells are vulnerable to injury as its low tolerance of heat. The effect of thermal ablation will significant increased while more proportion of hypoxic cells. Although the blood vessels expand, blood flow accelerate and enhance metabolism of cells in tissues at the heating begin. But then the blood flow slow down and get stasis, accumulation of acidic metabolites, the PH value decreased within the tissues, so that increased the sensitivity of cells to heat in the acidic environment, thus the effect of thermal ablation become more significant. The mechanism of RF ablation producing high temperatures which lead to cells of tumor get damage show as below: (a) Affect tumor cell membrane structure and fluidity, thus affecting a variety of tumor cell membrane function. (b) Increase the activity of lysosomes of tumor cells, as destruction of a variety of organelles. (c) Killing local tumor cell while allowing the blood vessels around the tumor tissue coagulation to form a buffer zone, and prevent tumor metastasis. (d) Inhibition of tumor vessel growth, thereby killing tumor cells. (e) RF thermal effects can enhance the body's immune system as absorption of necrosis can stimulate the body's resistance of tumor generation.
Coagulation necrosis
The RF thermal tumor ablation therapy is focus on how to exterminate the whole tumor without leave the cancer cells by minimally invasive measure while avoiding damaging the adjacent tissues. Optimizing thermal generation and minimizing thermal energy loss in the given area should be considered in the effective ablation. The equation of bio-heat described previously by viewing thermal ablation simplified to a first approximation as:
Coagulation necrosis = energy deposited x local tissue interactions - heat lost[4]
Energy deposition
Much of the heat loss is caused by convection which is blood flow. Therefore, the practice of some companies is to improve the RF power to obtain greater energy deposition. Others began to improve the electrode probes, like internally cooled electrodes or multi-hooked expandable probes with several hooks on the needle. It is larger ablation zone by using these techniques than a single needle.
Traditional single polar electrodes
RF technology has been used in neurological and cardiac treatment at first. To deal with these operations, the traditional single polar electrodes could deal with the small and precisely ablation competently. To ablate the entire large tumor, by increasing the current, increasing the length and diameter, and increasing the reaction time is not enough. So that we need to modify the RF electrode probes.
Modification of RF probes
Internally cooling electrode probes
Internally cooling probe has a couple of lumens inside the needles. Cold saline solution is injected continuously, when it works. So that decreased the temperature near the probe, to prevent the tissue be carbonized and the thermocouple recorded the temperature close to the tissue. This will cause the heat of the settlement, the heat close to the probe will move downwards. At the same time it leading to increased conductivity near the needle. By using this measure, the zone of ablation which is the coagulation necrosis is much larger than the conventional monopolar electrode as the energy deposited into deeper tissue.
Multiprobe electrodes
In the use of monopolar electrode probe will find the cylindrical probe does not match with the spherical tumor size. At first, people insert electrode repeatedly to increase the diameter of ablation zone. Obviously, this is not a good measure to destroy the entire tumor. Therefore, multi-hooked expandable probes were used as the next generation needle. By using this method, the ablation of diameter is more than 8 times compared with the monopolar electrode probe. But the multiprobe position is very difficult at the same time. So that the RF electrodes were created like mushroom which enable ablate the larger zone. In the end of operation, the coagulation on the needle can be recycled with the hooks, so that to achieve the purpose of preventing the spread of cancer cells. The design which has 12 hooks[5], can more effectively ablate the large tumor (3~5cm).
Bipolar electrodes
Comparing with the Traditional single polar electrodes, there is not only the active probe but also have a ground probe. However, the zone of ablation is different from the normal tumor. Therefore, the effectiveness of this approach is not very significant. Another design based on bipolar electrodes have both active and return probes, but lack the experience of using this method.
Pulsed radiofrequency ablation
Pulsed RF ablation is a measure to enhance the average energy by laser achieve the purpose of get more energy deposition. The high energy deposition and the low energy deposition are exchanging fast, when the pulse working. If we have the optimal pulse frequency, so that the tissue temperature close to the probe will be cooling, and the deep tissue could keep heat during a period time. This measure has combination with the internally cooling electrode probes, can have a positive effect each other even ablation in the large tumor tissue.
There is another type of probe which is working by measuring the impedance of the tissue rather than the temperature. The device has external insulation materials, which has 10 flexible needles inside. This device will continue to work until a rapid increase in resistance suddenly. When the tissue heat to dehydrated, the impedance will increase. Normally, the device will be completely stopped, when the ablation is done.
RFA computational study
The process of the RFA combines a serious of electrical, thermal activity and even some fluid motion. So the mathematical mode of the RFA is varying according to different physical parameter accounted in. The basic process is the high frequency electric current flowing into the issue by the ablation probe. The issues will generate the volumetric heat. At the same time, the heat will exchange in the issue with thermal conductivity. Because some coupling problem between electricity and thermo can be formulated, the corresponding mathematical mode would be initiated.
Recently, the finite element models of RFA have been researched numerously. by the finite element analysis, the electric field and temperature distribution surrounding the ablation probes could be stimulated and predicted. Date from these models, one major difference is the assumption of the electrical properties. In some early modes, the electrical properties of the issues such as the electrical conductivity are regarded as a constant [7,8]. In these cases, the modal is simplified tremendously. Because the bi-directional coupling problem between the electrical and thermal problems is separated, furthermore, the thermal calculation is relying on the electric property, but the electrical field is independent. So the calculation won't be iterative, Enormous calculation is reduced. The D. Haemmerich's work is based on this assumption. They regard the conductivity of the tumor is both 0.4 S/m at 20 kHz and at 500 kHz, the conductivity of the healthy liver tissue is 0.2 S/m at 20 kHz, and 0.4 S/m at 500 kHz.
Its conclusion is that RF ablation processing at lower frequencies will produce larger lesions, preferentially within the boundaries of the tumor [7].
Some researchers have shown that the electrical conductivity of issues is temperature, and material dependent. The coupling problems will become be-directional between electricity and thermo, as the modal using temperature-dependent electrical conductivity. As the result, the thermal profile and the electrical property are interdependent
The researchers want to know what extent the constant electrical properties could be simplified and the amount of error result when temperature-dependent phenomenon are ignored. So the researcher designs the experiment that one assumption the electrical conductivity is constant. Another one is that the electrical conductivity is assumed that it is temperature-dependence and its behavior is similar to the that of an equivalent sodium chloride solution [9].The data of the experiment indicates that the results of using temperature-dependent electrical property in finite element models is significant different. According to the data, the conclusion is that it is necessary to consider the temperature-dependent electrical properties in the mode. the difference between results with constant electrical conductivity and that with temperature-dependent conductivity is about 5-8%. This might be a significant deviation when designing the ablation system by mathmatical models. Another conclusion is that temperature-dependent phenomena may make big changes in the energy deposited into tissues. The study indicates that energy deposited is directly affected by temperature-dependent phenomena.
Overall, temperature-dependent electrical conductivity is used more frequently in the modal of the RFA [10-13].Using the finite element analysis can also use to found the relations between the temperature and the lesion during the RFA process, because the temperature is often used to describe the predicted size of the lesions. But from the stimulation result, it is concluded that the temperature isotherms may not represent actual tissue damage [13].
For more precise stimulating the RFA process, there is another factor should be taken into consideration. During the RFA process, the tissue may be carbonized which will extremely reduce the quality of the ablation. Because the tissue carbonization will block the heat transfer from the probe into the issue, some RFA processes used cooled-tip ablation probes to inject flow of sodium chloride into the active part.
As the infiltration flow of the injected solution added into the modal, the overall heat transfer process in the RFA has changed and the process is more complex. The flowing fluid will transfer the heat by advection. The advection expands the heated zone and makes the peak temperature at the point near the electrode lower compared to the case of purely conductive heat exchange. The magnitude of the transferred heat power at each point depends on the velocity of the fluid. So to stimulate these combined processes of the heat transfer, the hydraulic conductivity partial differential equations and the advection-diffusion equation should be solved.
So in the mathematical description of RFA, the heating of the tissue by high frequency electrical current and the heat conductivity and advection mechanisms all should be taken into account. This classical modal investigates the process as a probe inserted into tumor tissue [14]. The geometry of the probe is like a hallow needle of diameter 2mm insert into the liver tissues 60mm. the tip 20mm of the probe is electrically active. The tissue is assumed as a cylinder around the point where the probe inserts into. The diameter of the cylinder is 120mm. The NaCl solution is infiltrated into the tissue through eyeholes of the hollow ablation probe, fills in the intercellular spaces and spreads over the investigated liver zone. The velocities of the fluid at each point of the zone are calculated by solving the fluid flow equations.
The whole modal is divided into four aspests. (1) Electrical current(2) Infiltration of fluid(3) Thermal phenomena(4) Damage of the tissue(5) Coupling of multi-physical phenomena.
(1) Electrical current
The model is quasi-static and the varying voltage and the electrical current is described as their effective values by means of the equation
Where is the electric potential, the electrical conductivity of the tissue. And ,the radial and axial coordinates.
(2 )Infiltration of fluid
Because the ablation processes is in ex vivo tissues, the only fluid flow is due to the infiltration of NaCl solution. Considering there is only small blood vessels around the vicinity of the probe. So the influence of the blood vessels is ignored. The influence process is described by using the hydraulic conductivity equation based on Darcy's law
Where p is the pressure presented as hydraulic head, k the hydraulic conductivity coefficient of the tissue, the hydraulic capacity of the porous media.
(3) Thermal phenomena
Thermal field in the tissue is described by the heat diffusion advection
equation as
Where T is the temperature of the tissue, b the volumetric density of heat source,the thermal conductivity, c the mass thermal capacity, and p the mass density.
(4) Damage of the tissue
The damage of the tissue due to heating is obtained by Arhenius formula, which defines the value of the "damage integral" as
Where c(t) is the concentration of live cells, R the universal gas constant, A the "frequency" coefficient, and the energy of initiation of irreversible ablation reaction.
(5) Coupling of multi-physical phenomena
The coupling of the electric and thermal fields takes place due to the dependency of the electrical conductivity on the temperature of the tissue and due to the volumetric heat generation rate the magnitude of which is dependent on the electric current strength. Values of electrical conductivity of liver tissues at different temperatures are not comprehensively investigated at the time being. In practical
calculations the electrical conductivity of the tissue is usually identified with the electrical conductivity of NaCl solution of normality N and temperature T , which has been expressed as
Where is the electrical conductivity of the normality N solution at temperature 25.The normality
of physiological NaCl solution is N ≈ 0.105.
The expression of the volumetric heat generation rate reads as
Where is the power generated by the flow of electric current through the issue, the heat power losses due to blood flow perfusion, , the mass thermal capacity and mass density of the blood, the perfusion coefficient and the heat power generated due to metabolic process.
The dependence of electrical conductivity of the tissue against is damage integral has to be taken into account by scaling tissue electrical conductivity as
The computed result of this modal of the RFA process is similar to the experimentally obtained data both in space and in time. So it is practicable to use this model to predict the temperature distribution characteristics in the tissues and the optimal insert point of the ablation probe.
Future improvement of the RFA models should include better understanding of real structure and in homogeneity of liver tissue. And more deeply study of fluid flow process and heat exchange inside of the ablation probe in order to obtain reliable estimations of injected NaCl temperatures at the injection eyeholes of the ablation probe. The dependence of the volumetric saturation fraction (VSF) from temperature explicitly as our experimental data did not provide sufficient background to determine the necessary relationship. More refined experiments should be designed to clarify the problem, possibly analyzing the dependence of VSF not only on the temperature, but on the extent of damage of the cells as well.
Application
RFA is very useful for cancers, people did a great deal of research on treating tumor with RFA.
(1) Lung cancer
Lung cancer is one of the most common cancer in the world and take the first place for the people who is over 60. Unfortunately, the survival rate is very low. 5-years survival rate is 14%. Previous studies have shown that radiofrequency ablation (RFA), as an alternative management for lung malignancies, has advantages over traditional radiation therapy and systemic chemotherapy.7
Yeong Hun Choe, So Ri Kim and somebody else did a RFA treatment on 65 patients with lung malignancy while 6 patients underwent PTC (percutaneous thoracic cryotherapy). And then they evaluated the results of RFA and PTC, such as efficacies, survive rate, complications and local progression rate. Last they found that after treatment, 29 patients with RFA treatment completely attained ablation at the same time the complete ablation rate was even higher with the small-size lung mass (≤3cm), the rate reached 76.2%. Their study proved evidence for the use RFA as treatment alternatives with low procedural morbidity in the management of inoperable pulmonary
malignant tumours.
They use the RFA under CT(computed tomography) guidance. All of the patients underwent chest CT (Somatom Plus 4 or Sensation 16, Siemens, Erlangen, Germany) before performing procedures, and scans which were obtained within the area of interest depending on the size of the lesion were selected.
They performed RFA with 17-gauge, single or clustered internally cooled radiofrequency electrodes. In order to minimise the incidence of pneumothorax, they restrict the number of electrode accross the pleura to a single insertion. If an additional ablation was required, they changed the position of the needle within the tumour by putting it into upper tissue, making a different angle, and then inserting it again into the target without totally remove the electrodes from pleura. Once the position of the electrode was confirmed as correct, they attached the electrode to a 500-kHz monopolar radiofrequency generator (CC-1, Radionics, Burlington, Massachusetts, USA) which can produce an 150-200W's output. Then they record the tissue impedance by circuitry incorporated in the generator. At the end of each treatment, they stopped the perfusion and record the maximal temperature. If the temperature exceeded 60 ℃, the electrode was withdrawn in adding 1 cm to the length of the active tip; while, they also gained the intratumoural temperature. If, after the first treatment, the maximal intratumoural temperature did not exceed 60 ℃, they added an additional treatment at the same site which is based on descriptions of tumour ablation performed in other organ systems, in the first step radiofrequency ablation last for 12 min and then 6-12 min for the next step, with a maximum peak current of 1000-2000 mA and 80-150W. After the ablation procedure, the electrode was removed without cauterising the probe tract.
In their work, all patients underwent helical CT before the ablation, immediately after RFA and had the last one at 1 month later. So the result was gained on the basis of post-treatment CT scans obtained the immediately ones.
Their results as flows, complete ablation was attained in twenty-nine patients (43.3%) treated with RFA. At the same time they found the results was analysed according to tumour size (63.0 cm versus >3.0 cm). The complete ablation rate for the target lesions by RFA was significantly higher in smaller sized tumours than those in tumours larger than 3.0 cm (Fig. 1A). The rate of complete ablation by RFA was 76.2% for tumours smaller than 3.0 cm and 28.3% for tumours larger than 3.0 cm (Fig. 1B).
FIG1
During the observed period, forty-two (64.6%) patients expired. The overall median survival duration was 20.8±4.7 months with 1-, 2-, and 3-year survival rates of all patients being 67%, 46% and 27%.
As a result, they thought RFA has bright future, it is very useful to use it for malignancy especially for those are smaller than 3 cm in diameter.
Marcello Carlo Ambrogi , Marco Lucchi also do some work on treating cancer with RFA, between Oct 2001 and June 2005 they perform 88 RAFs of lung tumours. At last, they found in 86 examples, the finally result was technically successful. At a mean in the following 23.7 months, they recorded a 61.9% of complete responses, with a higher rate in the metastatic lesions (70.8%) and in those smaller than 3 cm (69.7%). Mean (median) overall survival. And local progression-free interval were 17.3 (28.9) months and 12.9 (24.1) months, respectively
They try the treatment in this way: utilising a generator which is able to provide monopolar radiofrequency energy to perform coagulation and ablation of soft tissue (Model 1500, RITA Medical System, Mountain View, CA, USA). This is an automatic apparatus with a max power output of 150 W, the working frequency is 460 Hz. It could display more than one temperature at once and monitor the power. The energy was transferred into the tissue by means of a multitined expandable array (StarBrust XL, RITA Medical system) which consists of a 15-gauge needle cannula with nine deployable electrodes which open flower-like up to 5 cm (Fig. 2). Five electrodes are equipped with thermocouples in order to allow continuous measure the temperature of the tissue. They applied two grounding pads to each leg in order to reduce risks of skin because of heat injuries. So when the system was powered on, the operator set the parameters of the ablation: the mode of operation (they utilised 'average temperature mode', in which delivered power was automatically regulated to maintain the target temperature set); the target temperature; the ablation time at target temperature; the maximum power delivery level, either of which can be changed during the treatment.
Fig2
They also use CT as guide to get more information about effectiveness, the result was thirty-one of 54 (60%) patients were alive, and among these 24 (77%) were locally disease-free (LDF); of the patients who were deceased 15 (65%) were LDF. Distant recurrence (mediastinal, pulmonary or other sites) occurred in 21 (39%) patients (5 of them were LDF). Most of these patients underwent some adjuvant therapy (CT and/or RT). Mean overall survival and local progression-free interval (LPI) were 17.3 and 12.9 months, respectively. They were related to the size of the tumour, both showing a difference between lesions smaller than 3 cm and those equal or greater than 3 cm. Survival was 19.7 months for lesions smaller than 3 cm and 12.1 months for those greater (p = .02), while LPI was 15.8 and 6.6 months, respectively ( p = .002).
Next, they did some examinations to test their lung function, they determined the forced expiratory volume, and fund it decreased at 1 month from RFA then raised, finally, became the same as pre-RFA.
In their opinion, the effect of RFA in mid-to-long period if the safety and the feasibility are solved but, it is do a middle way of high risk surgical resection and the quality of life.
It is easy to say RFA which is useful for lung tumor.
(2)Liver cancer
Hepatocellular carcinoma (HCC) is one of the most frequently occurring tumours worldwide and often occurs in cirrhotic livers. Although the orthotopic liver transplantation (OLT) can increase up to 92% of five year survival, the lack of donor became the limit of this treat measure. Furthermore, high recurrence rate makes situation worse.
Therefore, complementary techniques such as radiofrequency thermal ablation (RFA) have evolved for the management of patients with primary and secondary liver tumours.
A.Casaril , M. Abu Hilal have determined the treatment using RFA on liver cancer to be a possible way. They did a clinical application on 130 consecutive patients. The result is only one died because of perforation of the colon and other fives had major complications. There were 15 minor complications. Local recurrence rates reached 30% overall, and a further 25 patients developed a new hepatic lesion, different from the one treated by RFA. Median disease-free survival was 13 months. Overall survival rates at 1, 2 and 5 years were 85.3%, 71.3% and 57.6%, respectively.
They did in this way: Three doses of antibiotic prophylaxis were used (cefazolin 1 g every 8 h; Totacef, Bristol-Myers Squibb S.p.A., Sermoneta (LT), Italy). Under local anaesthesia and sedation, a 0.5 cm incision (subcostal or intercostal) was performed and the needle was inserted under ultrasound guidance, if the diameter was less than 3 cm. When the diameter was more than 3 cm or the shape was not regular the point of insertion was in the deepest part of the nodule. The tines were deployed and the generator switched on. The duration of the procedure was usually 12 min at 100 ℃. Real-time monitoring by ultrasonography was not possible at the beginning of their experience because of the interference created by the electromagnetic field, but it can be used sometimes later with the use of new needles and generators.
If it need further treatment which is judged by the ultrasound result, a new thermal burn could be obtained simply by retracting the needle along the insertion line or completely removing the needle and reinserting it with a new trajectory. When a satisfactory ultrasound pattern was obtained (a hyper-echoic image, due to gas bubbles, 1 cm greater than the previous image of the nodule), the tines were retracted and the needle removed. They used an expandable needle with four, seven or nine tines, connected to a 50 or 150 W RF generator (RITA Medical System, Mountain View, CA, USA), as previously described.19
The finally result is twenty-five patients (30%) developed local recurrence over the time frame of this study. A further 25 patients (30%) developed a new hepatic lesion. Overall survival at 1, 2 and 5 years was 85.3%, 71.3% and 57.6%, respectively. Median disease-free survival was 13 months. Overall disease free survival at 1, 2 and 5 years was 50.8%, 39.8% and 29.5%, respectively.
So they thought RFA is an effective technique for the treatment of selected hepatic tumours. Mortality rates and the incidence of major and minor complications are low.
(3) breast cancer
Breast is one of the most malignancy in woman's life, the morbidity of breast cancer accounts 7-10% in the hole body's malignancy. With the technology development, RFA became effective method to treat this tumour.
Jonathan F. Head and his team did this treatment on 5 patients, the radiofrequency probe (25 cm, 14 gauge, 9 array, 5 thermocouple; RITA Medical Systems, Mountain View, CA) was inserted after stereotactic localization and the RFA proceeded for 20 min at an average temperature of 75 ℃. Four of the tumors were invasive ductal carcinomas (IDC) and one was a ductal carcinoma in situ (DCIS). The first three patients were done under local anesthesia with light sedation, while the last two had an intercostal nerve block to improve pain control. The probe array was able to penetrate all four of the invasive ductal carcinomas but was not able to penetrate the DCIS. The first case had the area resected 6 weeks after the ablation, however, the three successive IDC cases were not resected and they have been followed by clinical examination and mammography. The last two patients had 40 mg depo-medrol instilled in the ablation cavity and were placed on anti-inflammatory protocol in an attempt to prevent inflammatory fat necrosis at the site of the RFA. None of the patients received postoperative radiotherapy.
Comments
According to bio-thermal theory, measures of ablation can be divided as (a) by changing the conductivity of the tissue to increase the total energy deposition; (b) improve the heat retention capacity in the tissue; (c) reduce the heat tolerance of tumor tissue. The energy deposited is mainly depended on the conductivity of tissue which is surrounding the probe, in the same current conditions. Prior inject the saline solution into the tumor tissue or change the conductivity of tissue during using the RF current. Thus get a better energy deposition, as well as the effect of heating and coagulation. The best dose of salt solution must determined by the type of applied RF device and the type of the tumor tissue. High concentrations of salt solution will cause excessive tissue conductivity. There is a competitive relationship between the increase in electrical conductivity and the RF ablation. It improves the energy deposition and better heating effect. But also increases the energy requirements of the device produced. If this value exceeds the maximum output of the device, only less coagulation will be generated in fact. In the real clinical application, it is always difficult to obtain a uniform liquid distribution. Even if having injection solution at the same time, they cannot get the same coagulation zones normally. Injection of the solution may cause distortion of the shape of the ablation zone. The overflow of solution may cause a lot of small resistances around the target. Injecting a small amount of solution could increase the ablation zone without generating a lot of leakage.
The root reason of heat loss
There is sufficient evidence to prove that the main reason for RF ablation heat loss is caused by blood flow. RF ablation is more limited compared to ex vivo tissue in vivo tissue. In the highly vascular tissue, temperature range from 50°C to 60°C is not enough to achieve ablation energy deposition. RF ablation of coagulation in vivo tissue is determined by the adjacent vasculature.
Pharmacologic regulation has a distinct effect of blood flow as well[6]. Intraarterial vasopressin and halothane have significant impact of blood flow. Based on experimental observations, people get several methods which used for slow the blood flow in the RF ablation. In the laparotomy surgery, the measure which to occlude all the portal inflow is usually used. There are many other pharmacological methods feasible in the theory, but only be considered in the experimental stage now.
Reducing the tumor tolerance to heat are strategies which have been proposed as well. But it still have many problems which need well study.
