Laparoscopic applicator and system for laparoscopic ablation

Abstract

This invention provides devices and laparoscopic ablation systems for use in laparoscopic surgery. [Solution] The device for use in laparoscopic surgery comprises a shaft 201 having a distal end and a proximal end; a holding unit positioned at the distal end of the shaft 201 and configured to hold and / or release tissue; at least two electrodes 209_n incorporated within the holding unit; a force transmission unit positioned on the shaft, connected to the holding unit and configured to move relative to the shaft; and a conductive line positioned within the shaft and connected to the at least two electrodes and configured to send electrical signals to be received via the proximal end of the shaft to the at least two electrodes.

Description

Technical Field

[0001] The present invention relates to the field of minimally invasive medical procedures, particularly focusing on ablation techniques, specifically irreversible electroporation (IRE) of tissue. IRE is an advanced technique used in interventional medicine for tissue-targeted treatment. Such a technique represents a significant advancement in medical treatment and has already been suitably used for ablation of cardiac tissue, particularly considering tissue selectivity, shortened treatment time, and minimization of the risks of conventional treatment methods.

Background Art

[0002] In recent years, the treatment of tissue by pulsed electric fields has been increasingly established as an important clinical technique. However, the use of short high-voltage pulses and the accompanying high electric field strength acting on tissue have been the subject of intensive research for more than 40 years. This application method is classified as a non-thermal method. This is because this application method is based on the supply of short high-voltage pulses that generate a locally strong electric field in the range of up to several thousand volts per centimeter between the active electrode pairs, and thus is classified as non-thermal processing. This electric field strength forms pores in the cell membrane in a short time. When the electric field exceeds a specific threshold required to form pores in the lipid bilayer of the cell membrane and the tissue is exposed to this electric field for a critical time, the cells die by apoptosis.

[0003] Pulsed field ablation has been shown to be a promising treatment method for arrhythmias such as atrial fibrillation. However, nerve modulation using pulsed high-voltage electrical signals remains the subject of many research projects. One important research area is renal denervation (renal nerve removal), a method to suppress increased sympathetic nerve activity in the treatment of hypertension and other cardiovascular diseases. The current treatment is a minimally invasive procedure that uses a special catheter to block nerve pathways around the renal artery. The catheter is introduced into the renal artery, and nerve fibers extending outside the artery through the vessel wall are destroyed by thermal or chemical ablation.

[0004] While the aforementioned minimally invasive intravascular catheter-based approaches for nerve modulation are considered promising treatment methods, some of the studies conducted have raised doubts about their effectiveness. For example, since renal sympathetic nerve fibers are located outside the arteries and cannot be directly reached by catheters, laparoscopic procedures for perivascular nerve modulation (laparoscopic perivascular nerve modulation therapy) may be a promising alternative. This method allows for direct contact between nerve fibers and laparoscopic ablation instruments, increasing the likelihood of treatment success.

[0005] Irreversible electroporation (IRE) is a virtually non-thermal procedure that uses only minimal electrical energy, resulting in a tissue temperature increase of only a few degrees Celsius. This clearly distinguishes it from conventional RF ablation (RF: radiofrequency), which raises tissue temperature by 20-70 degrees Celsius, causing thermal cell destruction. Conventional RF ablation typically uses bipolar pulses, combining positive and negative electrical pulses, to adequately avoid muscle contractions that occur when using DC voltage. Such pulses can be applied between the two bipolar electrodes of an applicator, or between the applicator electrode and a surface electrode, usually placed on the patient's back.

[0006] For an IRE pulse to generate perforation within tissue, the electric field strength E, defined by the pulse on the tissue between at least two electrodes, must exceed a tissue-dependent threshold Eth. For example, the threshold is approximately 500 V / cm for cardiac cells, while it is approximately 3000 V / cm for osteocytes. This difference in thresholds allows for the selective use of IRE in various tissues. The voltage to be applied to the electrode pair to achieve the required electric field strength depends on the target tissue, as well as the distance between electrodes and the electrode size itself. Similarly, these parameters affect the amount of thermal energy input during ablation and, consequently, the temperature peak that may occur in the treated tissue. The applied voltage can reach several kilovolts, which is significantly higher than the typical voltage of 10-200 V in thermal RF ablation.

[0007] Established systems on the market for nerve modulation, particularly for renal denervation, employ transvascular catheter-based approaches using RF energy or ultrasound. However, a common drawback of transvascular nerve modulation is that ablation of the outer nerve bundle requires ablation that penetrates the vessel wall. To overcome this, there is an alternative treatment using a laparoscopic applicator. The laparoscopic applicator is inserted into the patient's torso and can treat nerves around arteries perivascularly from the outside. This reduces the amount of energy required into the tissue, thereby increasing the success rate of nerve modulation and minimizing the risk of vascular damage.

[0008] Such laparoscopic systems for perivascular nerve conditioning, such as renal denervation, are known under specification EP4335397A1. This document describes an ablation device having an electrode unit that surrounds a tubular tissue piece and can remove nerves using a thermal ablation method (e.g., radiofrequency ablation). [Overview of the Initiative] [Problems that the invention aims to solve]

[0009] Improvements to the ablation approach are needed. [Means for solving the problem]

[0010] This invention relates to laparoscopic ablation, and more particularly to laparoscopic neuromodulation therapy.

[0011] For this purpose, the apparatus described in claim 1 and the system described in claim 15 are proposed.

[0012] According to a first aspect, a device for use in laparoscopic surgery is proposed. The device has a shaft. The shaft has a distal end and a proximal end. The device has a retaining unit located at the distal end of the shaft. The retaining unit is configured to hold and / or release tissue. The device has at least two electrodes located in / on / integrated with the retaining unit. The electrodes are directly and / or permanently connectable to the retaining unit. The device has a force transmission unit located on / in the shaft and connected, for example, indirectly to the retaining unit, wherein the force transmission unit is configured to move relative to the shaft. The device has a conductive line located in the shaft and particularly conductively connected to at least two electrodes, and is configured to transmit electrical signals received via the proximal end of the shaft to at least two electrodes, in particular, to perform irreversible electroperforation on / in / in the tissue.

[0013] The device is also called a laparoscopic applicator. The device may have a trocar configured to insert a shaft through the patient's torso.

[0014] The device may have an articulated joint. The articulated joint can be positioned between the retaining unit and the distal end of the shaft. The articulated joint can be positioned at the distal end of the shaft and / or, in particular, directly connected to the distal end of the shaft. The articulated joint may be configured to connect the distal end of the shaft to the retaining unit in a particularly movable manner. The operation of the force transmission unit can result in the operation of the retaining unit, and / or the retention and / or release of tissue by the force transmission unit. The operation of the force transmission unit can result in the operation of the articulated joint, and the operation of the articulated joint can result in the operation of the retaining unit, and / or the retention and / or release of tissue.

[0015] The holding unit can be configured as a finger gripper, specifically a two-finger or three-finger gripper. The force transmission unit can be configured as a tension / compression rod. In particular, the movement of the tension / compression rod relative to the shaft can cause the finger gripper to open and close in order to grasp / clamp or release tissue.

[0016] The device may have a longitudinal axis, a transverse axis, and a height axis. The shaft may extend along the longitudinal axis. The tension / compression rod can be configured to move along the longitudinal axis. In particular, the movement of the tension / compression rod along the longitudinal axis results in opening and closing movements of the finger gripper along the height axis and / or transverse axis, especially in the planes of the height axis and the longitudinal axis.

[0017] Each finger of the finger gripper has an inner surface, which is directed toward and / or in contact with the tissue, particularly when the finger gripper is closed. One of at least two electrodes (particularly ablation electrodes), particularly one of multiple electrodes, can be integrated into / on the interior of at least one of the at least two inner surfaces. At least two of the multiple electrodes can be configured as ablation electrodes. At least three of the multiple electrodes can be configured as measurement electrodes.

[0018] The holding unit can be configured as a suction unit. The operation of the force transmission unit can be arbitrarily set in the range of 0° to 90° (including these values) in particular, by the angle of the suction unit relative to the shaft, for example, the angle in the plane of the height and longitudinal axes. The suction unit can be configured to aspirate tissue and / or to be fixed to or separated from the tissue.

[0019] The suction unit may have a suction trough. The suction unit may have at least one suction hole located in the suction trough. The suction unit may have a suction channel connected to at least one hole. The suction unit may have a suction port provided at one end of the suction channel. An external vacuum pump is connected via the suction port to generate negative pressure in the suction trough and aspirate tissue into / into the suction trough. Alternatively, the suction trough can be separated from the tissue by turning off the external vacuum pump or reducing the negative pressure in the suction trough.

[0020] The suction trough can be configured to be elliptical, particularly stadium-shaped or circular, along the height axis. At least two electrodes, particularly ablation electrodes, can be positioned within the suction trough along and / or across the height axis.

[0021] A suction trough may have a trough width and trough length. The suction trough can be fabricated from a flexible material. For example, the width of the suction trough can be (slightly) adjusted when aspirating tissue. This allows the suction trough to conform to the structure and / or shape of the tissue being aspirated.

[0022] The suction trough can be configured in an elliptical shape along the height axis, particularly in a stadium shape or circular shape. At least three electrodes, particularly measuring electrodes, can be positioned in addition to, for example, at least two electrodes, along the height axis and / or laterally relative to the height axis, within the suction trough, particularly at least two electrodes, separated by a first electrode distance. At least two / three electrodes can be positioned along the height axis in the upper / lower region (inside) of the suction trough, while at least three / two electrodes can be positioned laterally relative to the height axis in the lower / upper region (inside) of the suction trough. More specifically, at least two electrodes (e.g., ablation electrodes) can be positioned along the height axis in the upper region (inside) of the suction trough, while at least three electrodes (e.g., measuring electrodes) can be positioned laterally relative to the height axis in the lower region (inside) of the suction trough. Alternatively, at least three electrodes (e.g., measurement electrodes) can be positioned along the height axis in the lower region (inside) of the suction trough, while at least two electrodes (e.g., ablation electrodes) can be positioned laterally with respect to the height axis in the upper region (inside) of the suction trough.

[0023] The holding unit can be configured as a shell gripper, particularly as two split shell grippers. The operation of the force transmission unit can be set to any angle of the shell gripper relative to the shaft, particularly the angle in the plane of the lateral and longitudinal axes, particularly within the range of 0° to 90° (including these values), and / or the shell gripper can be opened and closed.

[0024] The shell gripper may extend along the transverse axis and / or have a maximum extension. The shell gripper may be configured to open and close along the height axis. At least one of the two electrodes may be integrated, for example, inside each shell, particularly at least or exclusively one shell, particularly along the longitudinal axis and / or laterally relative to the longitudinal axis. At least two electrodes, particularly the ablation electrode, may be integrated inside each shell, particularly along the longitudinal axis and / or laterally relative to the longitudinal axis.

[0025] The shell gripper can extend / spread along the lateral axis and / or have its maximum spread. The shell gripper may be configured to open or close along the height axis. For example, inside each shell, in particular at least or exclusively one shell, at least three electrodes (at least one of them), in particular a measurement electrode, in addition to at least two electrodes, in particular an ablation electrode, can be integrated, in particular along the longitudinal axis and / or laterally relative to the longitudinal axis and / or separated from at least two electrodes by a second electrode distance. Inside each shell, at least three electrodes, in particular a measurement electrode, can be integrated, in particular along the longitudinal axis and / or laterally relative to the longitudinal axis.

[0026] At least two / three electrodes can be arranged in the upper / lower region along the longitudinal axis inside the shell, and at least three / two electrodes can be arranged transversely to the longitudinal axis in the lower / upper region. Alternatively, more specifically, at least two electrodes (e.g., ablation electrodes) can be arranged along the longitudinal axis inside the shell in the upper region, and at least three electrodes (e.g., measurement electrodes) can be arranged transversely to the longitudinal axis in the lower region. Or, at least three electrodes (e.g., measurement electrodes) may be arranged along the longitudinal axis in the lower region inside the shell, and at least two electrodes (e.g., ablation electrodes) may be arranged transversely to the longitudinal axis in the upper region.

[0027] The force conduction unit can be configured as a first tension / compression rod arranged in the shaft and connected to the joint structure. By the operation of the first tension / compression rod, the shell gripper opens and closes. The force conduction unit can be additionally configured as a second tension / compression rod arranged in the shaft and connected only to the shell gripper. The operation of the second tension / compression rod can arbitrarily set the angle of the shell gripper with respect to the shaft, for example, a predetermined angle, for example, an angle within the plane of the longitudinal / lateral axis, especially in the range of 0° to 90° (including these values).

[0028] The force conduction unit and the holding unit can be configured as shape memory materials in close contact with each other, especially shape memory alloys. The holding unit can be configured as a capture structure, especially a capture basket. By the operation of the force conduction unit, the capture structure, especially the capture basket, can move and deploy from the shaft or retract into the shaft and fold.

[0029] The capture structure, particularly the capture basket, can have two individual splines and three mutually adjacent splines. At least two electrodes, particularly ablation electrodes, and / or (in addition to at least two electrodes) at least three electrodes, particularly measurement electrodes, can be integrated onto the splines, particularly onto the mutually adjacent splines. The three mutually adjacent splines can have the form of two stadia-shaped splines connected on their longitudinal sides.

[0030] According to a second aspect, a system for laparoscopic ablation, particularly for perivascular neuromodulation, is proposed. The system has the device according to the first aspect. The system has a signal generator device connected or connectable to the device. The system has a control and evaluation unit connected or connectable to the device and / or the signal generator device.

[0031] The signal generator device can have a first signal generator that generates a first signal, particularly a radio frequency (RF) signal, and a second signal generator that generates a second signal, particularly a signal for pulsed field ablation.

[0032] The advantage of this is that the combination of an RF signal and pulsed field ablation is made possible within one system, and the overall procedure of laparoscopic ablation is shortened. Normally, for this purpose, two separate systems that apply either an RF signal or pulsed field ablation are used, and these systems have to be alternately inserted into the patient's chest.

[0033] The control and evaluation unit can be configured to control the first signal generator and / or the second signal generator to send signals.

[0034] The control and evaluation unit can be configured to generate a signal by controlling a first signal generator and / or a second signal generator in response to the temperature of at least one electrode. The control and evaluation unit can be configured to generate a signal by controlling the first signal generator when the electrode temperature falls below a temperature limit. The control and evaluation unit can be configured to generate a signal by controlling the second signal generator when the electrode temperature reaches or exceeds a temperature limit.

[0035] The control and evaluation unit can be configured to apply current to at least two electrodes and / or measure the voltage between at least three electrodes, and from the current and voltage, the nerve activity of the tissue and / or local tissue impedance can be determined.

[0036] According to a third aspect, a method for perivascular and / or perineurial nerve modulation is proposed. The method comprises inserting an applicator into a patient. The method comprises positioning the distal end of the applicator in the patient's blood vessel, tissue, or nerve. The method comprises positioning the distal end of the applicator in the patient's blood vessel, tissue, or nerve and bringing at least two electrodes of the applicator into perivascular and / or perineurial contact with the area around the blood vessel, tissue, or nerve. The method comprises performing denervation by supplying energy through at least two electrodes. The energy is supplied using a protocol that includes at least one pulsed field ablation (PFA). The method comprises withdrawing the applicator.

[0037] An irreversible electroporation method can be performed by the method according to the third embodiment.

[0038] A reversible electroporation method can be performed by the method according to the third embodiment.

[0039] The distal end of the applicator may also be positioned in tissue to accommodate placement in blood vessels, tissue, or nerves. A power generation system may be provided for performing denervation. The power generation system may be integrated into the distal end of the applicator or electrically connected to at least two electrodes located distal to the applicator.

[0040] The applicator can be inserted by laparoscopy. In addition to or instead of this, the applicator can also be removed by laparoscopy.

[0041] The laparoscopic applicator can be inserted into the patient's torso via a trocar. The applicator may have a trocar. The applicator may further comprise a shaft having a distal end and a proximal end. The distal end may have, for example, multiple electrodes.

[0042] The applicator can be inserted by surgical intervention. In addition to or instead of this, the applicator can also be removed by surgical intervention.

[0043] After insertion of the applicator, the geometric deployment of the distal end of the applicator can be initiated. This allows for the creation of a distal end shape that conforms to blood vessels, tissues, or nerves. Deployment can be controlled by mechanical, magnetic, or material-based control.

[0044] The applicator electrodes can be brought into contact with the target blood vessel, tissue, or nerve.

[0045] The method may further include confirming the applicator's positioning by local impedance measurement. For example, the applicator's positioning can be considered complete when at least two electrodes are in contact with blood vessels, tissue, or nerves. The positioning can then be confirmed.

[0046] The protocol may include, for example, only PFA pulses.

[0047] The protocol may include a combination of PFA pulses and radio frequency (RF).

[0048] The method may further include selecting whether the energy supply for denervation should be performed by a protocol using PFA pulses or by a protocol using a combination of PFA pulses and RF pulses.

[0049] Energy may be supplied once or multiple times to the same or different sites within blood vessels, tissues, or nerves. Energy can be supplied by PFA pulses or by a combination of PFA pulses and RF pulses.

[0050] Denervation can enable, or result in, perivascular and / or perineurial neural modulation. This eliminates the need for neural modulation that penetrates the blood vessel wall, thus avoiding this process.

[0051] The method may further include quantifying the conductivity of blood vessels, tissues, or nerves using at least two stimulation-measurement electrodes before denervation. The quantification of conductivity can be performed using a stimulation-measurement device having stimulation-measurement electrodes positioned proximal and distal to at least one ablation electrode.

[0052] The method may further include characterizing the denervated area using at least two stimulation-measurement electrodes after denervation. Characterization of the denervated area can be performed using a stimulation-measurement device having stimulation-measurement electrodes positioned proximal and distal to at least one ablation electrode.

[0053] During the procedure described, the temperature of the ablation site selected for ablation may be measured. In other words, the method may further include measuring the temperature of the selected ablation site while the procedure is being performed.

[0054] Further features, characteristics, advantages, and possible modifications will become apparent to those skilled in the art from the following description with reference to the attached drawings. [Brief explanation of the drawing]

[0055] [Figure 1] This is a schematic diagram of a biphasic IRE pulse according to the embodiment. [Figure 2] This is a schematic diagram of a pulse protocol using multiple biphasic pulse bursts according to an embodiment. [Figure 3] This is a schematic diagram of a treatment protocol that combines at least one biphasic IRE pulse burst and at least one RF energy burst 120, according to a modified embodiment. [Figure 4] This figure shows an embodiment of the distal portion of a laparoscopic applicator. [Figure 5] This is a schematic diagram showing how to control the aforementioned electrodes in order to perform neuromodulatory procedures. [Figure 6] This diagram shows the configuration of the distal portion of a laparoscopic applicator. [Figure 7] This is a schematic diagram showing the electrode placement within the suction trough and the control options for performing neuromodulatory procedures. [Figure 8] This figure shows one embodiment of the distal portion of a laparoscopic applicator. [Figure 9] This figure shows another embodiment of the distal portion of a laparoscopic applicator. [Figure 10] This figure shows a schematic sequence for performing laparoscopic nerve conditioning, using denervation as an example. [Modes for carrying out the invention]

[0056] Figure 1 is a schematic diagram showing a two-phase IRE pulse (irreversible electroporation) according to one embodiment, where the voltage V of the two-phase PFA pulse 100 is shown as a function of time t in the IRE ablation method. In this embodiment, the second signal generator is referred to as the IRE generator, and the IRE generator is configured as a voltage source. Therefore, the IRE signal is described here in the form of its voltage. The two-phase IRE pulse 100 includes a positive pulse 101 and a negative pulse 104. The terms "positive" and "negative" refer to the independently selected polarities of two electrodes controlled for ablation, and a two-phase pulse is applied between these electrodes. The amplitude of the positive pulse 101 is denoted as kV+ and lasts for a time 102. Similarly, the amplitude of the negative pulse 104 is denoted as kV- and has a duration 105. There is a delay time 103 between the two pulse phases 101 and 104. Both temporal pulse widths 102 and 105, as well as amplitudes kV+ and kV-, can be set independently of each other and therefore can be varied in exemplary embodiments of the present invention.

[0057] Figure 2 is a schematic diagram showing a pulse protocol with biphasic pulse bursts according to one embodiment. Over the duration of IRE procedure 113, pulses 100 are supplied in the form of one or more bursts or pulse packets 110. Each burst 110 contains a specified number N biphasic pulses 100, each pulse separated by a time interval 111. There is also a delay time 112 between the supply of each burst 110.

[0058] Figure 3 is a schematic diagram showing a procedure protocol relating to a modified embodiment, in which a burst of at least one biphasic IRE pulse is combined with at least one RF energy burst 120. Over the duration of the combined complete procedure 113, the RF energy and IRE pulses are supplied in the form of one or more bursts 120 and 110. Each IRE burst contains a specified number N bipolar pulses 100, each pulse separated by a time interval 111. The RF burst is represented by a sinusoidal signal having amplitude RF_A and duration 121. The RF burst is followed by a delay time 122. Both the duration of the RF burst and the subsequent delay time 122 can be controlled based on the temperature currently measured at the ablation electrode. A delay time 112 exists between the supply of individual IRE bursts 110. A delay time 123 exists between an IRE burst and a new supply of RF bursts.

[0059] Figure 4 shows a modified example of the distal section of a laparoscopic applicator. The applicator has a shaft 201 that can be inserted into the patient's torso using a trocar 210. A tension / compression rod 200 extends inside the shaft 201. The tension / compression rod is freely movable along the longitudinal axis Lx and relative to the shaft. The distal end of the applicator is provided with three-finger grippers 206, 207, each having a two-finger section 206 and a one-finger section 207. Each of the three fingers has an inner surface, particularly a concave bulge. The three-finger grippers 206, 207 are configured to grasp a cylindrical tissue structure whose periphery is formed around a transverse axis Ly. The tissue structure has a longitudinal extension parallel to the transverse axis Ly of the laparoscopic applicator. To realize the gripper mechanism, the three-finger grippers 206 and 207 are attached to the outer shaft 201 and the inner tension / compression rod 200 via joint structures 202, 203, 204, and 205. When the tension / compression rod 200 moves along the longitudinal axis Lx, gripping is performed by the three-finger grippers. This makes the gripping distance 208 variably adjustable and adaptable to various tissue structures. Multiple electrodes 209_n are provided in the concave bulges of the three-finger grippers 206 and 207. Each concave bulge has an electrode. Each electrode 209_n is connected to an evaluation / control unit (not shown) and a power generation system (not shown) via electrical contacts extending inside the shaft 201. These electrodes are each exposed to the external environment, but the electrical connections to the control unit and power generation system are isolated from the external environment. In this embodiment, the electrodes are configured as ablation electrodes, thereby enabling laparoscopic ablation.

[0060] Figure 5 is a schematic diagram showing how to control the aforementioned electrode 209_n to perform nerve modulation. In this embodiment, electrodes 209_2 and 209_3 are placed in the two-finger portion 206, and electrode 209_1 is placed in the one-finger portion 207. Control option 1 generates a radial electric field. For this purpose, a voltage Vr is applied between electrode pairs 209_2 and 209_1, and between electrode pairs 209_3 and 209_1. When all electrodes are in contact with tissue structure, a radial current is generated. In control option 2, a current along the lateral axis Ly is induced by generating an electric field by applying a voltage Va between electrode pairs 209_2 and 209_3. Here, electrode 209_1 is non-functional and electrically floats.

[0061] Figure 6 shows a further embodiment of the distal portion of a laparoscopic applicator. The applicator has an outer shaft 301 that can be inserted into the patient's torso using a trocar 310. A tension / compression rod 300 extends inside the shaft 301 and is freely movable along its longitudinal axis Lx and relative to the shaft 301. The distal end of the applicator is provided with a suction unit 311 equipped with a flexible, non-traumatic suction trough 306, which can contact cylindrical tissue structures by negative pressure. The suction trough 311 is connected to the shaft 301 and the tension / compression rod 300 via joint structures 302, 303, 304, and 305, allowing for free adjustment of the angle 314 between the longitudinal axis Lx of the shaft 301 and the suction unit 311. The adjustable angle allows for both insertion by the trocar 310 and optimal contact with the tissue structure. The suction trough 306 has multiple suction holes 307 inside, which are connected to a suction channel 312. The suction trough has a predetermined trough width 313. At the outlet of the suction channel 312 is a vacuum connection part 315, and when the vacuum connection part is connected to an external vacuum pump, negative pressure is generated inside the suction trough 306.

[0062] Figure 7 is a schematic diagram showing the electrode device positioned within the aspiration trough 306 and the control options for performing the neuromodulatory procedure. Electrode device 1 (left) is provided with two ablation / stimulation electrodes 316_1 and 316_2, and three measurement electrodes 317_1, 317_2, and 317_3. All electrodes are oriented perpendicular to the longitudinal axis of the aspirated cylindrical tissue structure. By applying a predetermined current to the two electrodes 316_1 and 316_2, baseline nerve stimulation can be performed with this electrode pair at the start of the procedure. The three measurement electrodes 317_1, 317_2, and 317_3 are used to measure nerve conductivity during simultaneous stimulation. For this purpose, two bipolar voltages are recorded and processed via electrode pairs 317_1 and 317_2, and electrode pairs 317_2 and 317_3. Following such baseline measurements, bipolar ablation is performed via electrode pairs 316_1 and 316_2. To evaluate the characteristics of neuromodulation, the nerve conduction measurement and analysis described above are performed again after ablation. The order of these procedures is the same in electrode device 2 (right), but the arrangement of electrodes inside the suction trough 306 is different. In this configuration, all electrodes are arranged parallel to the longitudinal axis of the aspirated cylindrical tissue structure. Two ablation / stimulation electrodes 318_1 and 318_2 are placed to the right of the multiple suction holes 307, and measurement electrodes 319_1, 319_2 and 319_3 are placed to the left of the multiple suction holes 307.

[0063] Figure 8 shows a modified distal section of a laparoscopic applicator. The applicator has an outer shaft 401 that can be inserted into the patient's torso using a trocar 410. A tension / compression rod 400 extends inside the shaft 401 and is freely movable along the longitudinal axis Lx. The distal end of the applicator is provided with a double split-shell gripper, which has a first split-shell 406 and a second split-shell 407. Each split-shell has a concave bulge and is configured to grasp cylindrical tissue structures. To realize the gripper mechanism, the double split-shell gripper is connected to the outer shaft 401 and the inner tension / compression rod 400 via joint structures 402, 403, 404, 405, 414, and 415, so that when the tension / compression rod 400 moves along the longitudinal axis Lx, the first split-shell 406 and the second split-shell 407 are gripped. The resulting gripping distance 408 is thus variably adjustable and adaptable to various tissue structures. A second tension / pressure rod 412 extends inside the shaft 401 and is connected to the first half-shell 406 and the second half-shell 407, allowing adjustment of the angle 416 between the longitudinal axis Lx of the shaft 401 and the two half-shell grippers. The adjustable angle 416 enables insertion using the trocar 410 and optimal contact with the tissue structure. Multiple ablation / stimulation electrodes 420_n and measurement electrodes 421_m are positioned in the concave bulges of the first half-shell 406 and the second half-shell 407. These electrodes are individually connected to an evaluation / control unit and a power generation system (neither shown) via electrical contacts extending inside the shaft 401. These electrodes are each exposed to the external environment, but the electrical connections to the control unit and the power generation system are isolated from the external environment. In the embodiment with two ablation / stimulation electrodes and three measurement electrodes, the control is the same as described in Figure 7.

[0064] Figure 9 shows a further embodiment of the distal portion of a laparoscopic applicator. The applicator has an outer shaft 601 that can be inserted into the patient's torso using a trocar 610. Extending inside the shaft 601 is a capture structure, particularly a capture basket, made from, for example, a shape memory material. The capture basket consists of three closely spaced splines 604 and two separate splines 602 and 603. The entire capture structure is highly elastic, allowing it to be fully retracted into the shaft 601. The capture structure is configured to grasp and wrap around a cylindrical tissue structure in the illustrated state. Stimulation / ablation electrodes 605_n and multiple measurement electrodes 606_m are positioned on the three closely spaced splines 604, respectively. The multiple electrodes 605_n and 606_m are individually connected to an evaluation / control unit and a power generation system (neither shown) via electrical contacts extending inside the shaft 601. Each electrode is exposed to the external environment, but the electrical connections to the control unit and power generation system are isolated from the external environment. In the embodiment with two ablation / stimulation electrodes and three measurement electrodes, the control is the same as described in Figure 7.

[0065] Figure 10 shows a schematic procedure 500 for performing laparoscopic nerve conditioning in an embodiment of denervation. One or more of the steps described with reference to Figure 10 can be performed using a laparoscopic applicator as illustrated with reference to Figures 4, 6, 8, and 9. In the first step 501, the applicator system, in particular a laparoscopic applicator, is inserted into the patient laparoscopically. As illustrated with reference to Figures 4, 6, 8, and 10, the laparoscopic applicator has a trocar, through which the shaft of the laparoscopic applicator can be inserted into the patient's torso. After positioning the applicator, it is confirmed whether the electrode is in sufficient and good contact with the tissue by measuring the local impedance at the ablation electrode (step 502). In the next step 503, an initial value of nerve conductivity is recorded using, for example, the mechanism described with reference to Figure 7. For example, one or more nerves can be supplied with a stimulation pulse by applying a predetermined current to the distal or proximal electrode of the ablation electrode. The resulting bipolar voltage is measured at the measurement electrode pair during simultaneous stimulation and is used to evaluate the characteristics of nerve conduction. Subsequently, in step 504, one can choose between two types of procedures or input options, namely denervation using pulsed field ablation (PFA) or a combined procedure of PFA and RF-energy. In the case of PFA denervation (step 505), the procedure, in particular energy delivery, is performed using an exemplary protocol with biphasic IRE pulses as shown in Figure 2. If the PFA-RF combined procedure (506) is selected, the procedure, in particular energy delivery, is performed using the combined protocol illustrated in Figure 3. Regardless of the selection of the denervation method, nerve activity is newly recorded (507) for evaluation of the characteristics of denervation (508), as described in Figures 7, 8, and 9.

[0066] This specification describes laparoscopic neuromodulation using a combination procedure consisting of a continuous sequence of IRE and radio frequency (RF) in addition to an advantageous applicator. This allows for continuous temperature monitoring while increasing the conductivity of the target tissue. This maximizes the success rate of irreversible electroporation and reduces the generation of potentially harmful high current densities. The use of an applicator eliminates the need for ablation that penetrates the vessel wall.

Claims

1. A device used for laparoscopic surgery, A shaft having a distal end and a proximal end, A retaining unit positioned at the distal end of the shaft and configured to hold and / or release tissue, At least two electrodes incorporated within the holding unit, A force transmission unit is positioned on the shaft, connected to the holding unit, and configured to move relative to the shaft, A conductive line is disposed within the shaft and connected to the at least two electrodes, configured to send an electrical signal to be received via the proximal end of the shaft to the at least two electrodes, A device having.

2. The apparatus according to claim 1, further comprising a joint structure disposed between the holding unit and the distal end of the shaft, wherein the joint structure is configured to connect the distal end of the shaft to the holding unit, particularly movably, and the operation of the force transmission unit causes the holding unit to operate and / or the force transmission unit to hold and / or release the tissue.

3. The apparatus according to claim 1 or 2, wherein the holding unit is configured as a finger gripper, particularly a three-finger gripper, and the force transmission unit is configured as a tension / pressure rod, and the finger gripper opens and closes to grasp or release the tissue by the operation of the tension / pressure rod.

4. The apparatus according to claim 3, wherein the fingers of the finger gripper have an inner surface facing the tissue, particularly when the finger gripper is closed, and at least one of the at least two electrodes, particularly one of the plurality of electrodes, is integrated into the inner surface.

5. The apparatus according to claim 1 or 2, wherein the holding unit is configured as a suction unit, and the operation of the force transmission unit causes the suction unit to tilt with respect to the shaft and / or the suction unit to suck up or separate the tissue.

6. The aforementioned suction unit is Suction trough, At least one suction hole provided in the suction trough, A suction channel connected to at least one of the suction holes, and / or A suction port provided at one end of the suction channel, to which an external vacuum pump can be connected, wherein a negative pressure is generated in the suction trough via the suction port, and the tissue is drawn into the suction trough; The apparatus according to claim 5, having the following features.

7. The apparatus according to claim 6, wherein the suction trough is configured in an elliptical shape, particularly stadium-shaped or circular, along the height axis, and the at least two electrodes are arranged in the suction trough along the height axis and / or laterally with respect to the height axis.

8. The apparatus according to claim 6 or 7, wherein the suction trough is configured in an elliptical shape, particularly stadium-shaped or circular, along the height axis, and at least three electrodes are arranged within the suction trough, particularly at a distance from the at least two electrodes, along the height axis and / or laterally with respect to the height axis.

9. The apparatus according to claim 1 or 2, wherein the holding unit is configured as a shell gripper, particularly a split shell gripper, and the shell gripper is tilted with respect to the shaft and / or opens and closes as a result of the operation of the force transmission unit.

10. The apparatus according to claim 9, wherein the shell gripper extends along a lateral axis and is configured to open and close along a height axis, and the at least two electrodes are integrated inside at least one shell, particularly along the longitudinal axis.

11. The apparatus according to claim 9 or 10, wherein the shell gripper extends along a lateral axis and is configured to open and close along a height axis, and at least three electrodes are integrated inside at least one shell, particularly along the longitudinal axis and / or laterally with respect to the longitudinal axis, at a distance from the at least two electrodes.

12. The apparatus according to any one of claims 9 to 11, wherein the force transmission unit is configured as a first tension / pressure rod disposed within the shaft and connected to the joint structure, and the shell gripper opens and closes by the operation of the first tension / pressure rod, and / or the force transmission unit is configured as a second tension / pressure rod disposed within the shaft and particularly exclusively connected to the shell gripper, and the shell gripper tilts with respect to the shaft by the operation of the second tension / pressure rod.

13. The apparatus according to any one of claims 1 to 12, wherein the force transmission unit and the holding unit are made of a shape memory material, particularly a shape memory alloy, that is in close contact with each other, the holding unit constitutes a capture structure, particularly a capture basket, and by the operation of the force transmission unit, the capture structure, particularly the capture basket, retracts and folds into the shaft, or the capture structure, particularly the capture basket, moves to the outside of the shaft and unfolds.

14. The apparatus according to claim 13, wherein the capture structure has two separate splines and three closely spaced splines, and the at least two electrodes and / or at least three electrodes are integrated with the splines, particularly the closely spaced splines.

15. A system for laparoscopic ablation, The apparatus according to any one of claims 1 to 14, A signal generating device connected to or connectable to the aforementioned device, A control and evaluation unit connected to or connectable to the aforementioned device and / or the aforementioned signal generator, A system that has

16. The system according to claim 15, wherein the signal generating device comprises a first signal generator for generating a radio frequency RF signal and a second signal generator for generating a signal for pulsed field ablation.

17. The system according to claim 15 or 16, wherein the control and evaluation unit is configured to control the first signal generator and / or the second signal generator.

18. The system according to claim 17, wherein the control and evaluation unit is configured to control the first signal generator and / or the second signal generator in order to output a signal corresponding to the temperature of at least one electrode.

19. The system according to claim 18, wherein the control and evaluation unit is configured to activate the first signal generator and output a signal when the electrode temperature falls below a temperature limit, and to activate the second signal generator and output a signal when the electrode temperature reaches or exceeds the temperature limit.

20. The control and evaluation unit is configured to apply a current to at least two electrodes and / or measure the voltage between at least three electrodes, and the nerve activity and / or local tissue impedance of the tissue can be determined from the current and the voltage, or can be determined, according to any one of claims 15 to 19.

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