WO2012080394A1

WO2012080394A1 - System for the electrochemical prevention of needle tract tumor seeding and method for using the system

Info

Publication number: WO2012080394A1
Application number: PCT/EP2011/072907
Authority: WO
Inventors: Antonio Ivorra Cano
Original assignee: Universitat Pompeu Fabra UPF
Current assignee: Universitat Pompeu Fabra UPF
Priority date: 2010-12-15
Filing date: 2011-12-15
Publication date: 2012-06-21
Anticipated expiration: 2013-06-15
Also published as: ES2366845B1; ES2366845A1

Abstract

The present invention relates to a system for the prevention of needle tract tumor cell seeding, comprising a percutaneous surgical instrument (1) with a distal part percutaneously introducible into a tissue (3) of a patient; an electric current generator (2) generating current with at least one direct current component with a first terminal (2a) connected to the proximal end (1a) of the instrument (1) and a second terminal (2b) connected to an electrode (4) applied to the skin of the patient, such that the instrument (1) acts as the first electrode, the contact electrode (4) acts as the second electrode and the tissue (3) acts as the electrolyte; the electric current generator (2) is capable of inducing a transient circulation of the current with the direct current component, between the part of the instrument (1) introduced into the tissue and the contact electrode (4), resulting in one of an average current density, measured on the surface in the percutaneously introducible part of the instrument (1), of at least a chosen current density in the range between 1 mA/cm² and 1000 mA/cm² for circulation periods between 0.1 seconds and 10 minutes, such that the product of the average current density by time is greater than 50 mA.s/cm² and less than 10000 mA.s/cm², for generating electrochemical reactions producing a sufficiently toxic microenvironment (5) in the tissue (3) around the part of the instrument (1) introduced into the tissue of the patient.

Description

SYSTEM FOR THE ELECTROCHEMICAL PREVENTION OF NEEDLE TRACT

TUMOR SEEDING AND METHOD FOR USING THE SYSTEM

Technical Field of the Invention

The present invention is comprised within the technical field of medical instruments, and it particularly relates to systems for the prevention of tumor seeding in biopsy, laparoscopic needle tracts and the like when the needles, after having been inserted into tumor tissue, are withdrawn through the tract in non-tumor tissues through which they have been inserted, and in which tumor seeding is prevented by means of applying an electric current to the needle.

Background of the Invention

According to the US National Library of Medicine of the National Institutes of Health, tumor or neoplastic seeding is defined as the local implantation of tumor cells by contamination of medical instruments and surgical equipment after the surgical removal. This effect caused by medical intervention can occur, for example, in laparoscopic interventions or when taking biopsies. In the particular case of needle- shaped instruments, such as those used for examining, separating or removing tumors, the term needle-tract seeding is used for the implantation of neoplastic cells along the instrument insertion tract into the tissue of the patient. The specific risk rates of this effect are the object of debate. Thus, in the case of breast cancer biopsies, the clinical impact greatly differs among existing studies, but even so it is considered to be a real preoccupying issue. In the case of biopsies of liver lesions, two recent evaluations (R. Stigliano, L. Marelli, D. Yu, N. Davies, D. Patch and A. K. Burroughs, "Seeding following percutaneous diagnostic and therapeutic approaches for hepatocellular carcinoma. What is the risk and the outcome? Seeding risk for percutaneous approach of HCC," Cancer Treat. Rev., vol. 33, pp. 437-447, Aug, 2007; M. A. Silva, B. Hegab, C. Hyde, B. Guo, J. A. Buckels and D. F. Mirza, "Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: to systematic review and meta-analysis," Gut, vol. 57, pp. 1592-1596, Nov, 2008) appear to indicate that the risk of seeding is greater than 2%.

Although this value appears to be, at first glance, relatively low, the truth is that it has been recognized that due to this phenomena the possibility of curing some patients has been lost and, as a consequence, it has been proposed to restrict the indications for percutaneous biopsy of the liver.

It is considered that needle tract tumor cell seeding can occur by cellular convection due to the entrance of blood into the tract, by cellular migration through torn tissues, and by cellular movement caused by the shank or the tip of the instrument while it is being withdrawn, the latter being the tumor cell seeding mechanism to which some investigators attribute particular relevance.

Several systems have been designed for preventing needle tract tumor seeding when biopsies are taken. Thus, devices are known for taking biopsies comprising a flexible material cover which prevents the tumor cells from being pushed out of the insertion tract. The drawbacks of devices of this type are the need to modify the currently existing biopsy devices, which results in thicker devices, and the fact that these devices do not actually minimize the possibility of tumor cell seeding caused by cellular migration or movement.

Methods are also known for causing heat cauterization or ablation of the tissues surrounding the needle tract by means of the heating it, as described, for example, in documents WO9614018A1 and US2003109802A1 , or by means of heating the tissues around the needle tract based on the Joule effect with radiofrequency currents, as described by P. F. Laeseke, T. C. Winter 3rd, C. L. Davis, K. R. Stevens, C. D. Johnson, F. J. Fronczak, J. G. Webster and F. T. Lee Jr, in "Postbiopsy bleeding in a porcine model: reduction with radio-frequency ablation-preliminary results," Radiology, vol. 227, pp. 493-499, May, 2003, and S. A. Dromi, J. Locklin and B. J. Wood, in "Radiofrequency cauterization: an alternative to reduce post-biopsy hemorrhage," Cardiovasc. Intervent. Radiol., vol. 28, pp. 681 -682, Sep-Oct, 2005. Devices of this type require thorough temperature control of the needle and of the environment, which requires at least one temperature sensor in the distal part of the probe and therefore the modification of the design because lack of temperature control can result in excessively high temperatures which can cause the patient discomfort, cause the needle to adhere to the cauterized tissue or, on the other hand, cause insufficient treatment of the tissue surrounding the needle tract, in addition to the risk of the heating damaging the samples taken.

Document WO2009156506A1 describes a biopsy needle having two electric conductors connected to a high frequency generator and arranged such that a high frequency alternating current flows between their ends, said flow taking place entirely in the tissue of the patient such that heat cauterization occurs in the tissue without directly heating the needle, thus preventing active tumor cell seeding and bleeding in the needle tract. Basically, this biopsy needle suffers from the same drawbacks in terms of the need for temperature control as those previously mentioned with reference to biopsy needles in which the needle is heated to achieve cauterization.

A solid tumor treatment based on electrochemical reactions which are chemical reactions occurring in the interface between a metal electrode and the biological medium and entailing electron transfer between the electrode and the biological medium when a direct current flows through the interface is also known. These reactions comprise oxidations and reductions involving chemical species of the electrode and of the biological medium. Some of the resulting species can, when released into the biological medium, damage tissue components or interfere with biological processes up to the point of compromising cell viability. These chemical reactions are induced for destroying solid tumors by means of metal needles introduced into the tumor and to which low currents are applied, this treatment being referred to as "electrochemical treatment". Current densities of the order of 100 mA/cm² are typically applied during tens of minutes or even hours to create ablation areas with diameters of the order of several millimeters or a few centimeters. These techniques are also known as "direct current treatment", "electrolytic ablation" or "electrolysis", although this last name is used in the field of hair removal in which these reactions are caused near hair follicles for permanent hair removal.

Description of the Invention

The object of the present invention is to overcome the drawbacks of the state of the art described above by means of a system for the prevention of needle tract tumor cell seeding, comprising a percutaneous surgical instrument with a proximal end, a distal end, a distal part percutaneously introducible into a tissue (3) of a patient and potentially causing the seeding phenomena, and an outer surface made of electrically conductive material between the proximal end (1 a) and the distal end (1 b); as well as an electric current generator connected to the needle through a first cable and, by means of a second cable, to a contact electrode applicable to the skin of a patient; and it is characterized in that

the electric current generator is a current generator with at least one direct current component with a first terminal connected to the proximal end of the instrument by means of said first cable and a second terminal connected to the electrode through said second cable, such that the instrument acts as the first electrode, the contact electrode acts as the second electrode and the tissue acts as the electrolyte;

the electric current generator is capable of inducing a transient circulation of the current with a direct current component between the part of the instrument introduced into the tissue and the contact electrode, resulting in one of an average current density measured on the surface of the percutaneously introducible part of the instrument, of at least a chosen current density in the range between 1 mA/cm² and 10000 mA/cm² for circulation periods between 0.1 seconds and 10 minutes, such that the product of the average current density by time is greater than 50 mA.s/cm² for generating electrochemical reactions producing a sufficiently toxic microenvironment in the tissue around the part of the instrument introduced into the tissue of the patient.

As is apparent, this system is compatible with most existing biopsy needles and laparoscopy instruments having an electrically conductive surface.

Preferably, for the purpose of assuring a sufficiently effective treatment in a brief time and at the same time minimizing unwanted neuromuscular stimulations and minimizing damage to the tissue healthy surrounding the part of the instrument introduced into the tissue, either by the excessive generation of toxic species, by heat induced by the Joule effect or by electroporation, the electric current generator is capable of inducing in the part of the instrument introduced into the tissue at least a chosen current density between 1 mA/cm², for a time interval comprised between 50 seconds and 10 minutes, and 200 mA/cm2, for a time interval comprised between 0.25 seconds and 30 seconds, and preferably between 5 mA/cm², for a time interval comprised between 30 seconds and 5 minutes, and 100 mA/cm2, for a time interval comprised between 1 second and 30 seconds. The product of the average current density must be greater than 100 mA.s/cm² and less than 4000 mA.s/cm².

The needle can be provided, close to its proximal end, with an electrically insulating cover which can be introduced to under the skin of the patient for the purpose of preventing electrochemical reactions from occurring in the area of the skin and in the tissue of the patient which are in contact with part of the needle covered by the cover.

As an alternative to a simple switch or button operated by the medical staff to start the application of the current before withdrawing the needle-shaped instrument, the system according to the present invention can be provided with detection means for automatically detecting the start of the withdrawal of the instrument from the tissue. These detection means can comprise a sensor and an impedance meter connected such that they detect increases in the impedance between the instrument and the contact electrode, for which purpose the impedance meter can be connected, for example, to the terminals of the electric current generator, and serving to detect the start of the withdrawal of the instrument from the tissue through the change of impedance taking place when the withdrawal of the instrument from the tissue starts. By means of the impedance meter, when the withdrawal of the instrument starts, the relative increase of the impedance between the instrument and the contact electrode is detected, the corresponding detected signal being able to be used to start the current supply by the electric current generator. On the other hand, the impedance meter can be used as a security measure in the following way: If the impedance meter detects the withdrawal of the instrument while the current is being applied, the system can detect the withdrawal and generate a warning signal to notify the medical staff so that the necessary measures can be taken to prevent possible unwanted effects, for example, heating, spasms, etc., or also to automatically reduce them as the instrument is being withdrawn and emitting a warning only when the withdrawal is excessively quick.

Alternatively, the detection means can comprise an acceleration sensor connected to the proximal end of the instrument.

The system according to the present invention can comprise current supply control means connected to the electric current generator for progressively increasing the electric current supplied by the electric current generator from zero until generating the chosen current density in the part of the instrument introduced into the tissue up to the chosen current density, and progressively reducing the electric current corresponding to the chosen current density from the chosen level to zero before withdrawing the instrument. The progressive increase and reduction prevent neuromuscular stimulations which occur when the current is applied or cut off abruptly and which result in the patient feeling uncomfortable and even suffering spasms.

The main reactions which are thought to take place in biological samples when inert electrodes are used, for example platinum needles, are the following:

2H₂0 0₂ + 4H⁺ + 4e (1 ) 2C1^" Cl₂ + 2e^~ (2) in the anode, i.e., the electrode connected to the positive pole of a generator, and

2H₂0 + 2e^" H₂ + 20H (3) in the cathode, i.e., at the negative electrode.

Therefore, the main reactions in the anode are the decomposition of water resulting in a pH drop and oxygen generation, and in the chloride ion oxidation resulting in chlorine generation, while in the cathode the main reaction is the decomposition of water into molecular hydrogen in gaseous state and hydroxyl ions resulting in a pH increase.

Additionally, when electrochemically soluble electrodes, such as for example copper, aluminum or stainless steel electrodes, are used instead of inert electrodes, other reactions releasing metal ions can also take place in the anode, such as for example: 2Al 2Al⁺³ + 6e^" (4)

Although the biological impact of the preceding reactions continues to be object of debate, it is commonly considered that the alterations induced with respect to the pH in the anode and in the cathode are key factors determining the ablation capacities of the electrochemical treatment.

In the context of the present invention and taking into account that most surgical needles are made of stainless steel, it is preferred that the needle acts as a cathode since the cathode therefore does not corrode, and because this allows generating supraphysiological pH in the aforementioned toxic microenvironment. Therefore, according to a preferred embodiment of the invention, the first terminal of the electric current generator is negative, such that the instrument acts as the cathode and the second terminal is positive, such that the contact electrode acts as the anode, to cause a pH of at least 8.5 and preferably between 10 and 13.8 in the tissues and fluids in contact with the part of the instrument being introduced into the tissue and causing the toxic microenvironment.

However, in some cases, such as for example in the case of disposable needles, it is also acceptable for the instrument to act as the anode. Therefore, in another embodiment the first terminal of the electric current generator is positive, such that the instrument acts as the anode and the second terminal is negative, such that the contact electrode acts as the cathode.

According to the invention, the percutaneously introducible part of the instrument (1 ) can be a needle, a laparoscopic instrument, etc. Likewise, the instrument can be a biopsy needle. Such needles can be made of stainless steel or another material the surface of which is conductive.

It must be mentioned that in the field of the electrochemical treatment of tumors it has been observed that the blood circulation in small vessels is interrupted around the cathodes. In the context of the present invention, this phenomenon is not only beneficial for increasing the cell death rate due to ischemia, but also because it provides the additional advantage of reducing or minimizing the post-biopsy bleeding.

The present invention also relates to a method for using the system described above for preventing needle tract tumor cell seeding. This method comprises generating, by means of the current generator connected to the proximal end of the instrument and to the contact electrode, a direct current for inducing in the part of the instrument introduced into the tissue, a flow of a chosen current density, measured on the surface of the part of the instrument introduced into the tissue, between 1 mA/cm² and 1000 mA/cm² for circulation periods between 0.1 seconds and 10 minutes, such that the product of the average current density by time is greater than 50 mA.s/cm² and less than 10000 mA.s/cm², and preferably an average current density chosen between 5 mA/cm² and 500 mA cm² for a time interval which meets the condition that that the product of average density by time is greater than 50 mA.s/cm² and less than 10000 mA.s/cm², for example greater than 100 mA.s/cm² and less than 4000 mA.s/cm², for generating electrochemical reactions producing a sufficiently toxic microenvironment in the tissue around the part of the instrument introduced into the tissue.

To obtain this product of average density, it is possible to induce a direct current with at least a chosen current density between 1 mA cm², for a time interval comprised between 50 seconds and 10 minutes, and 200 mA/cm², for a time interval comprised between 0.25 seconds and 30 seconds, and preferably between 5 mA/cm², for a time interval comprised between 30 seconds and 5 minutes, and 100 mA/cm², for a time interval comprised between 1 second and 30 seconds, respectively.

In a preferred embodiment of this method, a current density and a current application time producing a toxic microenvironment of a diameter of at least 0.05 mm, preferably between 0.1 and 2 mm, are further chosen.

When the first terminal of the electric current generator is negative, such that the instrument acts as the cathode and the second terminal is positive, such that the contact electrode acts as the anode, a current density capable of producing a supraphysiological pH, preferably a pH of at least 8.5, preferably between 10 and 13.8 in said toxic microenvironment is chosen.

In a preferred embodiment of the method the electric current supplied by the electric current generator is progressively increased from zero until generating the current density in the part of the instrument introduced into the tissue up to the chosen current density whereas, before withdrawing said part form the tissue, the electric current corresponding to the chosen current density is progressively reduced to zero.

The system can also be designed for applying, together with the direct current, an alternating current component for slightly heating the tissue, as is the case of electric hair removal devices.

It must be taken into account that both live tissues and, to a lesser extent, the instrument, such as, for example, a needle, are materials offering electric resistance to the current flow and therefore that certain heating inevitably occurs due to the Joule effect. For the maximum preferred values of the product of the density by time the heating of the tissues is significant but does not entail excessive protein denaturation causing the adhesion of the needle to the tissues. On the other hand, if the needle- shaped instrument consists of a biopsy needle in which the sample taken is maintained in a compartment close to the distal end, the temperature of the sample must be prevented from exceeding 55⁹C for time periods greater than 10 seconds to prevent damage which can alter subsequent analysis. However, in those cases in which the temperature increase does not entail a problem or it could even be beneficial to increase the efficiency of the electrochemical treatment or for providing additional advantages such as cauterization, an alternating component could be superimposed on the continuous component of the current. A similar strategy is currently used in hair removal systems.

Brief Description of the Drawings

Aspects and embodiments of the invention are described below based on the drawings, in which

Figure 1 is a schematic view of an embodiment of the system according to the present invention with a biopsy needle introduced into a localized tumor in the tissue of a patient;

Figure 2 is a schematic view showing the tissue of Figure 1 once the needle has been withdrawn leaving the corresponding tract surrounded by a toxic environment.

Reference numbers identifying the following documents appear in these drawings:

1 needle

1 a proximal end

1 b distal end

1 c insulating cover 2 direct current generator

2a first terminal

2b second terminal

2c first connection cable

2d second connection cable

3 tissue of the patient

3a skin of the patient

3b tumor

4 contact electrode

4a conductive gel

5 toxic environment

6 needle tract

7 detection means

8 current supply control means

9 control logic

Embodiments of the Invention

In the embodiment of the system according to the invention shown in Figure 1 , this comprises a percutaneous surgical instrument in the form of a conventional stainless steel needle -1 - with a proximal end -1 a- introduced percutaneously into the tissue -3- of a patient for taking a sample of a tumor -3b- through its distal end -1 b-, an electric direct current generator -2- and a contact electrode -4-, which can be a contact electrode in itself conventional of the type used for electrocardiograms, applied to the skin -3a- of a patient.

The generator -2- comprises a negative first terminal -2a- connected to the proximal end -1 a- of the needle -1 - by means of a first cable -1c- and a positive terminal -2b- connected to the electrode -4- through a second cable -2d-, such that the needle -1 - acts as the cathode, the contact electrode -4- acts as the anode and the tissue -3- acts as the electrolyte.

The electric current generator -2- is capable of generating direct current in the needle -1 - introduced into the tissue -3-, a chosen current density of 100 mA/cm² for a maximum of 60 seconds for generating electrochemical reactions producing a toxic microenvironment -5- with a pH greater than 9 in the tissue -3- around the needle -1 -.

The terminals -2a, 2b- of the electric current generator -2- are also connected to a sensor and an impedance meter -7- which serves for detecting the withdrawal of the needle -1 - from the tissue -3- through the change of impedance taking place when the withdrawal of the needle -1 - from the tissue -3- starts. When the withdrawal of the needle -1 - starts, the relative increase of the impedance between the needle -1 - acting as a cathode and the contact electrode -4- acting as an anode is detected by means of the impedance sensor -7-, the corresponding detected signal being able to be used for starting the current supply by the electric current generator -2-.

The electric current generator -2- is also connected to current supply control means -8- which allow progressively increasing the electric current supplied by the electric current generator -2- from zero until generating the chosen current density in the needle -1 - introduced into the tissue -3- up to the chosen current density, and progressively reducing the electric current corresponding to the chosen current density

-1 - from the chosen level to zero. The progressive increase and reduction prevent neuromuscular stimulations which occur when the current is applied or cut off abruptly causing discomfort to the patient and he/she could suffer spasms.

The electric current generator -2-, the impedance sensor -7- are connected to a control logic -9-, implanted, for example, in a computer, in which the current supply control means -8- are also integrated, in which the electric current parameters needed for establishing the chosen current density in the needle -1 - are programmed, starting the supply of the electric current depending on the signals from the impedance sensor -7- and carrying out the progressive increase of the electric current from zero until the current density in the needle -1 - reaches from zero to the chosen current density as well as the progressive decrease of the electric current from the chosen current density to zero.

Between the skin -3- of the patient and the contact electrode there is a conductive gel -4a- of the type used in electrophysiology. Taking into account that, in the chemical reaction which occurs when the electric current is applied, toxic species are not only produced in the cathode, i.e., in the needle -1 - but also in the anode, i.e., the contact electrode -4-, the function of this gel -4a- is to protect the skin -3- of the patient from damage such as electrochemical burns, i.e., the electric conduction is maintained but the toxic species which have been generated are prevented from reaching the skin -3- of the patient. The thickness of the gel -4a- is about 10 mm which offers sufficient protection for application times less than 60 seconds and electric fields of 10V/cm or less than the electric current, since at such magnitudes of the electric field, the speed of migration of the toxic species formed in the anode is approximately 0.1 mm/s. Alternatively, a large contact electrode -4- which due to its extension on the skin prevents burns in the skin -3a- of the patient can also be used. Close to its proximal end -1 a-, the needle -1 - is provided with an electrically insulating cover -1c- which is introduced to under the skin -3a- of the patient. This cover -1c- prevents electrochemical reactions from occurring in the area of the skin -3a- and in the tissue -3- which are in contact with the part of the needle -1 - covered by the cover -1 c-.

The system described above can be used for the prevention of needle tract tumor cell seeding by means of a method the embodiment of which will be described below.

When the needle -1 - has been introduced into the tissue -3- of the patient and its distal end -1 b- has penetrated into the tumor -3b-, and the contact electrode -4- has been placed on the skin -4a- of the patient, a sample of the tumor -3b- which is introduced into the needle -1 - is taken. Once the sample is taken, the electric current generator -2- is started. By means of the current supply control -8-, the electric current supplied by the generator -2- is progressively increased from zero until it reaches the chosen current density -for example 100 mA/cm²- in the needle -1 -. The chosen current density is maintained for a sufficient time, for example 30 seconds, so that the electrochemical reactions which form a toxic microenvironment -5- with a supraphysiological pH greater than 9 and a diameter of between 0.5 mm and 2 mm occur on the surface thereof in the tissue -3-, which can be of the soft type, for example lung, muscle or adipose tissue, around the needle -1 -. Once the application time of the chosen current density is completed and, before withdrawing the needle -1 - from the tissue -3- the electric current corresponding to the chosen current density is also progressively reduced to zero by means of the current supply control means -8-, the needle -1 - is completely withdrawn and the contact electrode -4- is removed from the skin -3a- of the patient.

Once the needle -1 - is withdrawn, as can be seen in Figure 2, the toxic microenvironment -5- surrounds the needle tract -6-. It has been proved experimentally that the toxic microenvironment -5- is maintained for a few minutes -for example between 5 min to 30 min- after the current in the needle has been cut and even when it has been withdrawn.

Claims

1 . - System for the prevention of needle tract tumor cell seeding, comprising a percutaneous surgical instrument (1 ) with a proximal end (1 a), a distal end (1 b), a distal part percutaneously introducible into a tissue (3) of a patient and an outer surface made of electrically conductive material between the proximal end (1 a) and the distal end (1 b); and an electric current generator (2) connected to the instrument (1 ) through a first cable (2c) and, by means of a second cable (2d), to a contact electrode (4) applicable to the skin of a patient; characterized in that

the electric current generator (2) is a current generator with at least one direct current component with a first terminal (2a) connected to the proximal end (1 a) of the instrument (1 ) by means of said first cable (1c) and a second terminal (2b) connected to the electrode (4) through said second cable (2d), such that the instrument (1 ) acts as the first electrode, the contact electrode (4) acts as the second electrode and the tissue (3) acts as the electrolyte;

the electric current generator (2) is capable of inducing a transient circulation of the current with the direct current component, between the part of the instrument (1 ) introduced into the tissue and the contact electrode (4), resulting in one of an average current density, measured on the surface in the percutaneously introducible part of the instrument (1 ), of at least a chosen current density in the range between 1 mA/cm² and

1000 mA/cm² for circulation periods between 0.1 seconds and 10 minutes, such that the product of the average current density by time is greater than 50 mA.s/cm² and less than 10000 mA.s/cm², for generating electrochemical reactions producing a sufficiently toxic microenvironment (5) in the tissue (3) around the part of the instrument (1 ) introduced into the tissue of the patient.

2. - System according to claim 1 , characterized in that the product of the average current density by time is greater than 100 mA.s/cm² and less than 4000 mA.s/cm²,

3. - System according to claim 1 or 2, characterized in that the electric current generator (2) is capable of generating in the part of the instrument (1 ) introduced into the tissue (3), at least a chosen current density between 1 mA cm², for a time interval comprised between 50 seconds and 10 minutes, and 200 mA/cm², for a time interval comprised between 0.25 seconds and 30 seconds, and preferably between 5 mA/cm², for an time interval comprised between 30 seconds and 5 minutes, and 100 mA/cm², for a time interval comprised between 1 second and 30 seconds.

4. - System according to claim 1 , 2 or 3, characterized in that the first terminal (2a) is negative, such that the instrument (1 ) acts as a cathode and the second terminal is positive, such that the contact electrode (4) acts as an anode, for producing a pH of at least 8.5 and preferably between 10 and 13.8 in said toxic microenvironment (5).

5. - System according to claim 1 , 2 or 3, characterized in that the first terminal (2a) is positive, such that the needle (1 ) acts as an anode and the second terminal is negative, such that the contact electrode (4) acts as a cathode.

6. - System according to one of claims 1 to 5, characterized in that the instrument (1 ) is provided, close to its proximal end (1 a), with an electrically insulating cover (1c) which can be moved by the rod of the percutaneously introducible part of the instrument (1 ) for preventing the formation of the toxic microenvironment (5) in the skin and in the regions of the underlying tissue (3).

7. - System according to one of the preceding claims, characterized in that it comprises detection means (7) for detecting the start of the withdrawal of the instrument (1 ) from the tissue (3).

8. - System according to claim 7, characterized in that the current detection means (7) comprise an impedance meter, for detecting increases in the impedance between the instrument (1 ) and the contact electrode (4).

9.- System according to claim 7, characterized in that the current detection means (7) comprises an acceleration sensor connected to the proximal end (1 a) of the instrument (1 ).

10.- System according to one of the preceding claims, characterized in that it comprises current supply control means (8) connected to the electric current generator (2), for progressively increasing the electric current supplied by the electric current generator (2) from zero until generating the chosen current density in the part of the instrument (1 ) introduced into the tissue (3) up to the chosen current density, and progressively reducing the electric current corresponding to the chosen current density (1 ) from the chosen level to zero before withdrawing the instrument (1 ).

1 1 .- System according to one of the preceding claims, characterized in that it is designed for applying, together with the direct current, an alternating current component for gently heating the tissue.

12.- System according to one of the preceding claims, characterized in that the percutaneously introducible part of the instrument (1 ) is a needle.

13.- System according to one of claims 1 to 1 1 , characterized in that the percutaneously introducible part of the instrument (1 ) is a part of a laparoscopic instrument.

14.- System according to one of claims 1 to 1 1 , characterized in that the instrument (1 ) is a biopsy needle.

15.- System according to one of claims 12-14, characterized in that the percutaneously introducible part of the instrument (1 ) is made of stainless steel.

16. - Method for using the system defined according to claim 1 for preventing needle tract tumor cell seeding, characterized in that it comprises generating, by means of the current generator (2) connected to the proximal end (1 a) of the instrument (1 ) and to the contact electrode (4), a direct current for inducing in the part of the instrument (1 ) introduced into the tissue (3), a chosen current density between 1 m A/cm ² and 1000 mA/cm² for circulation periods between 0.1 seconds and 10 minutes, such that the product of the average current density by time is greater than 50 mA.s/cm² and less than 10000 mA.s/cm², for generating electrochemical reactions producing a sufficiently toxic microenvironment (5) in the tissue (3) around the part of the instrument (1 ) introduced into the tissue (3).

17. - Method according to claim 16, characterized in that the product of the average current density by time is greater than 100 mA.s/cm² and less than 4000 mA.s/cm².

18.- Method according to claim 16 or 17, characterized in that it is generated at least in the part of the instrument (1 ) introduced into the tissue (3), at least a chosen current density between 1 mA/cm², for a time interval comprised between 50 seconds and 10 minutes, and 200 mA/cm2, for a time interval comprised between 0.25 seconds and 30 seconds, and preferably between 5 mA/cm², for a time interval comprised between 30 seconds and 5 minutes, and 100 mA/cm², for a time interval comprised between 1 second and 30 seconds.

19. - Method according to claim 16, 17 or 18, characterized in that a current density and a current application time producing a toxic microenvironment (5) of a diameter of at least 0.05 mm, preferably between 0.1 mm and 2 mm around the part of the instrument (1 ) introduced into the tissue (3) are chosen.

20. - Method according to one of claims 16 to 19, characterized in that the first terminal (2a) of the electric current generator (2) is negative, such that the instrument (1 ) acts as a cathode and the second terminal is positive, such that the contact electrode (4) acts as an anode, for producing a supraphysiological pH, preferably a pH of at least 8.5, preferably between 10 and 13.8 in said toxic microenvironment (5).

21 . - Method according to one of claims 16 to 18, characterized in that the first terminal (2a) is positive, such that the instrument (1 ) acts as an anode and the second terminal is negative, such that the contact electrode (4) acts as a cathode.

22. - Method according to one of claims 16 to 21 , characterized in that when the instrument (1 ) is introduced into the tissue (3), the electric current supplied by the electric current generator (2) is progressively increased from zero until generating the current density in instrument (1 ) up to the chosen current density, and, before withdrawing the instrument (1 ) from the tissue (3) the electric current corresponding to the chosen current density is progressively reduced to zero.

23.- Method according to one of claims 16 to 22, characterized in that the chosen current density is applied for a maximum time of 60 seconds.

24. - Method according to one of claims 16 to 23, characterized in that the chosen current density and its application time are selected such that a heating greater than 55^eC is not produced for more than 10 seconds in the part of the instrument (1 ) introduced into the tissue (3).

25. - Method according to one of claims 16 to 24, characterized in that an alternating current component is applied together with the direct current for gently heating the tissue.

26. Method according to one of claims 16 to 25, characterized in that a needle is used as the percutaneously introducible part of the instrument (1 ).

27. - Method according to one of claims 16 to 25, characterized in that a part of a laparoscopic instrument is used as the percutaneously introducible part of the instrument (1 ).

28. - Method according to one of claims 16 to 25, characterized in that the surgical instrument (1 ) is a biopsy needle.

29. - System according to one of the preceding claims, characterized in that a stainless steel needle is used as the surgical instrument (1 ).