Abstract:
An ablation system including a first probe extending through a first longitudinal lumen from a proximal end to beyond a distal end of a flexible shaft, a first electrode coupled to a distal end of the first probe, and a first conductor electrically coupled to the first electrode. The ablation system further includes a second probe extending through a second longitudinal lumen from the proximal end to beyond the distal end of the flexible shaft, a second electrode coupled to a distal end of the second probe, and a second conductor electrically coupled to the second electrode. The first and second probes are rotatable and translatable within the first and second longitudinal lumens respectively. Furthermore, the first electrode and the second electrode are rotatably and translatably positionable with respect to one another, via the first probe and the second probe respectively, to define a region therebetween.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a continuation application claiming priority under 35 U.S.C. §120 to U.S. patent application Ser. No. 13/890,589, filed May 9, 2013, entitled ELECTROPORATION ABLATION APPARATUS, SYSTEM AND METHOD, now U.S. Patent Application Publication No. 2013/0261389, which is a continuation application claiming priority under 35 U.S.C. §120 to U.S. patent application Ser. No. 12/694,452, filed Jan. 27, 2010, entitled ELECTROPORATION ABLATION APPARATUS, SYSTEM AND METHOD, now U.S. Pat. No. 8,449,538, which is a divisional application claiming priority under 35 U.S.C. §121 to U.S. patent application Ser. No. 11/706,766, filed Feb. 15, 2007, entitled ELECTROPORATION ABLATION APPARATUS, SYSTEM, AND METHOD, now U.S. Pat. No. 7,655,004, the entire disclosures of which are hereby incorporated by reference herein. 
         [0002]    This application is related to U.S. patent application Ser. No. 13/218,221, filed Aug. 25, 2011, entitled ELECTROPORATION ABLATION APPARATUS, SYSTEM, AND METHOD, now U.S. Pat. No. 8,425,505, U.S. patent application Ser. No. 12/635,298, filed Dec. 10, 2009, entitled ELECTROPORATION ABLATION APPARATUS, SYSTEM, AND METHOD, now U.S. Pat. No. 8,029,504, and U.S. patent application Ser. No. 11/706,591, filed Feb. 15, 2007, entitled ELECTRICAL ABLATION APPARATUS, SYSTEM, AND METHOD, now U.S. Patent Application Publication No. 2008/0200911, the entire disclosures of which are hereby incorporated by reference herein. 
     
    
     BACKGROUND 
       [0003]    Electrical therapy techniques have been employed in medicine to treat pain and other and other conditions. Electrical ablation techniques have been employed in medicine for the removal of diseased tissue or abnormal growths from the body. Nevertheless, there is a need for improved medical instruments to electrically ablate or destroy diseased tissue or abnormal growths from the body, such as cancer tissue. There may be a need for such electrical therapy techniques to be performed endoscopically. 
         [0004]    Electrical therapy probes comprising electrodes may be required to electrically treat diseased tissue. The electrodes may be introduced into the patient endoscopically to the tissue treatment region by passing the electrodes through the working channel of an endoscope. 
       SUMMARY 
       [0005]    In one general aspect, the various embodiments are directed to an ablation apparatus. In at least one embodiment the apparatus comprises an elongate shaft comprising a proximal end and a distal end, wherein the elongate shaft defines a first lumen extending between the proximal end and the distal end, and a second lumen extending between the proximal end and the distal end. The apparatus further comprises a first probe extending through the first lumen from the proximal end to beyond the distal end of the elongate shaft, wherein the first probe is rotatable and translatable within the first lumen and a second probe extending through the second lumen from the proximal end to beyond the distal end of the elongate shaft, wherein the second probe is rotatable and translatable within the second lumen. The apparatus further comprises a first electrode attached to a distal end of the first probe, wherein a first conductor is electrically coupled to the first electrode, and a second electrode attached to a distal end of the second probe, wherein a second conductor is electrically coupled to the second electrode. The first electrode and the second electrode are rotatably and translatably positionable with respect to one another, via the first probe and the second probe respectively, to define a region therebetween. 
         [0006]    In another general aspect, the various embodiments are directed to an ablation system. In at least one embodiment, the system comprises a flexible shaft defining a first longitudinal lumen and a second longitudinal lumen. The system further comprises a first probe extending through the first longitudinal lumen from a proximal end to beyond a distal end of the flexible shaft, wherein the first probe is rotatable and translatable within the first longitudinal lumen, a first electrode coupled to a distal end of the first probe, and a first conductor electrically coupled to the first electrode. The system further comprises a second probe extending through the second longitudinal lumen from the proximal end to beyond the distal end of the flexible shaft, wherein the second probe is rotatable and translatable within the second longitudinal lumen, a second electrode coupled to a distal end of the second probe, and a second conductor electrically coupled to the second electrode. The first electrode and the second electrode are rotatably and translatably positionable with respect to one another, via the first probe and the second probe respectively, to define a region therebetween. 
         [0007]    In yet another general aspect, the various embodiments are directed to an ablation device mountable on an elongate shaft comprising a distal end and a proximal end, wherein the elongate shaft defines a first lumen and a second lumen that extend between the distal end and the proximal end. In at least one embodiment the ablation device comprises a first probe extending through the first lumen from the distal end to the proximal end of the elongate shaft, wherein the first probe is rotatable and translatable within the first lumen, and a first electrode attached to a distal end of the first probe, wherein a first conductor is electrically coupled to the first electrode. The ablation device further comprises a second probe extending through the second lumen from the distal end to the proximal end of the elongate shaft, wherein the second probe is rotatable and translatable within the second lumen, and a second electrode attached to a distal end of the second probe, wherein a second conductor is electrically coupled to the second electrode. The first electrode and the second electrode are rotatably and translatably positionable with respect to one another, via the first probe and the second probe respectively, to define a region therebetween. 
     
    
     
       FIGURES 
         [0008]    The novel features of the various embodiments of the invention are set forth with particularity in the appended claims. The various embodiments of the invention, however, both as to organization and methods of operation, together with further objects and advantages thereof, may best be understood by reference to the following description, taken in conjunction with the accompanying drawings as follows. 
           [0009]      FIG. 1  illustrates one embodiment of an endoscopic ablation system. 
           [0010]      FIG. 2  is an enlarged view of one embodiment of a therapeutic/diagnostic probe of one embodiment of the endoscopic ablation system shown in  FIG. 1 . 
           [0011]      FIG. 3A  is a side view of a distal end of one embodiment of a therapeutic/diagnostic probe comprising a biopsy probe and an electrical therapy electrode assembly. 
           [0012]      FIG. 3B  is a sectional view of one embodiment of a therapeutic/diagnostic probe taken along section line  3 B- 3 B showing the geometric relationship between the electrodes and the diagnostic probes. 
           [0013]      FIG. 4  is a sectional view of the lower end of an esophagus and the upper portion of a stomach of a human being. 
           [0014]      FIG. 5  illustrates the use of one embodiment of an endoscopic ablation system to treat diseased tissue in the lower esophagus. 
           [0015]      FIG. 6  illustrates the use of one embodiment of an endoscopic ablation system to treat diseased tissue in the lower esophagus. 
           [0016]      FIG. 7  illustrates one embodiment of a necrotic zone defined by the geometry and placement of the electrical therapy electrodes. 
           [0017]      FIG. 8  is a sectional view taken along the longitudinal axis of one embodiment of an endoscopic ablation system shown in  FIG. 1 . 
           [0018]      FIG. 9  is an end view taken along line  9 - 9  of one embodiment of a therapeutic/diagnostic probe of the endoscopic ablation system shown in  FIG. 8 . 
           [0019]      FIG. 10  is a sectional view taken along line  10 - 10  of a rotation tube of the endoscopic ablation system shown in  FIG. 8 . 
           [0020]      FIG. 11  shows one embodiment of a distal portion of an endoscopic ablation system shown in  FIG. 1  partially inserted into the esophagus of a patient. 
           [0021]      FIG. 12  is a diagram of one embodiment of a control loop for one embodiment of an irreversible electroporation therapy procedure to treat diseased tissue as described herein. 
           [0022]      FIG. 13  illustrates one embodiment of an electrical scalpel for dissecting tissue. 
           [0023]      FIG. 14  is a graphical representation (graph) of electric field strength (along the y-axis) as a function of distance from an electrical therapy electrode under various conductivity environments near diseased tissue. 
           [0024]      FIG. 15  is a close up of the graph shown in  FIG. 14 . 
       
    
    
     DESCRIPTION 
       [0025]    The various embodiments described herein are directed to diagnostic and electrical therapy ablation devices. The diagnostic devices comprise biopsy probes. The electrical therapy ablation devices comprise probes and electrodes that can be positioned in a tissue treatment region of a patient endoscopically. An endoscopic electrode is inserted through a working channel of an endoscope. The placement and location of the electrodes can be important for effective and efficient therapy. Once positioned, the electrical therapy electrodes deliver electrical current to the treatment region. The electrical current is generated by a control unit or generator external to the patient and typically has particular waveform characteristics, such as frequency, amplitude, and pulse width. Depending on the diagnostic or therapeutic treatment rendered, the probes may comprise one electrode containing both a cathode and an anode or may contain a plurality of electrodes with at least one serving as a cathode and at least one serving as an anode. 
         [0026]    Electrical therapy ablation may employ electroporation, or electropermeabilization, techniques where an externally applied electrical field significantly increases the electrical conductivity and permeability of a cell plasma membrane. Electroporation is the generation of a destabilizing electric potential across biological membranes. In electroporation, pores are formed when the voltage across the cell plasma membrane exceeds its dielectric strength. Electroporation destabilizing electric potentials are generally in the range of several hundred volts across a distance of several millimeters. Below certain magnitude thresholds, the electric potentials may be applied across a biological membrane as a way of introducing some substance into a cell, such as loading it with a molecular probe, a drug that can change the function of the cell, a piece of coding DNA, or increase the uptake of drugs in cells. If the strength of the applied electrical field and/or duration of exposure to it are properly chosen, the pores formed by the electrical pulse reseal after a short period of time, during which extra-cellular compounds have a chance to enter into the cell. Thus, below a certain threshold, the process is reversible and the potential does not permanently damage the cell membrane. This process may be referred to as reversible electroporation (RE). 
         [0027]    On the other hand, the excessive exposure of live cells to large electrical fields (or potentials) can cause apoptosis and/or necrosis—the processes that result in cell death. Accordingly, this may be referred to irreversible electroporation (IRE) because the cells die when exposed to excessive electrical potentials across the cell membranes. The various embodiments described herein are directed to electrical therapy ablation devices such as electroporation ablation devices. In one embodiment, the electroporation ablation device may be an IRE device to destroy cells by applying an electric potential to the cell membrane. The IRE potentials may be applied to cell membranes of diseased tissue in order to kill the diseased cells. The IRE may be applied in the form of direct current (DC) electrical waveforms having a characteristic frequency, amplitude, and pulse width. 
         [0028]    Electroporation may be performed with devices called electroporators, appliances which create the electric current and send it through the cell. The electroporators may comprise two or more metallic (e.g., Ag, AgCl) electrodes connected to an energy source to generate an electric field having a suitable characteristic waveform output in terms of frequency, amplitude, and pulse width. 
         [0029]    Endoscopy means looking inside and refers to looking inside the human body for medical reasons. Endoscopy may be performed using an instrument called an endoscope. Endoscopy is a minimally invasive diagnostic medical procedure used to evaluate the interior surfaces of an organ by inserting a small tube into the body, often, but not necessarily, through a natural body opening. Through the endoscope, the operator is able to see abnormal or diseased tissue such as lesions and other surface conditions. The endoscope may have a rigid or a flexible tube or member and in addition to providing an image for visual inspection and photography, the endoscope enables taking biopsies, retrieving foreign objects, and introducing medical instruments to a tissue treatment region. Endoscopy is the vehicle for minimally invasive surgery. 
         [0030]    The embodiments of the electrical therapy ablation devices may be employed for treating diseased tissue, tissue masses, tissue tumors, and lesions (diseased tissue). More particularly, the electrical therapy ablation devices may be employed in minimally invasive therapeutic treatment of diseased tissue. The electrical therapy ablation devices may be employed to deliver energy to the diseased tissue to ablate or destroy tumors, masses, legions, and other abnormal tissue growths. In one embodiment, the electrical therapy ablation devices and techniques described herein may be employed in the treatment of cancer by quickly creating necrosis of live tissue and destroying cancerous tissue in-vivo. These minimally invasive therapeutic treatment of diseased tissue where medical instruments are introduced to a tissue treatment region within the body of a patient through a natural opening are known as Natural Orifice Translumenal Endoscopic Surgery (NOTES)™. 
         [0031]    A biopsy is a medical procedure involving the removal of cells or tissues for examination. The tissue is often examined under a microscope and can also be analyzed chemically (for example, using polymerase chain reaction [PCR] techniques). When only a sample of tissue is removed, the procedure is called an incisional biopsy or core biopsy. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. When a sample of tissue or fluid is removed with a needle, the procedure is called a needle aspiration biopsy. A procedure called “optical biopsy” may be employed where optical coherence tomography may be adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope  1  millimeter in diameter. Optical biopsy may be used to obtain cross-sectional images of internal tissues. 
         [0032]    Biopsy specimens may be taken from part of a lesion when the cause of a disease is uncertain or its extent or exact character is in doubt. Vasculitis, for instance, is usually diagnosed on biopsy. Additionally, pathologic examination of a biopsy can determine whether a lesion is benign or malignant, and can help differentiate between different types of cancer. 
         [0033]      FIG. 1  illustrates one embodiment of an endoscopic ablation system  10 . The endoscopic ablation system  10  may be employed to electrically treat diseased tissue such as tumors and lesions. The endoscopic ablation system  10  may be configured to be positioned within a natural opening of a patient such as the colon or the esophagus and can be passed through the opening to a tissue treatment region. The illustrated endoscopic ablation system  10  may be used to treat diseased tissue via the colon or the esophagus of the patient, for example. The tissue treatment region may be located in the esophagus, colon, liver, breast, brain, and lung, among others. The endoscopic ablation system  10  can be configured to treat a number of lesions and ostepathologies including but not limited to metastatic lesions, tumors, fractures, infected site, inflamed sites, and the like. Once positioned at the target tissue treatment region, the endoscopic ablation system  10  can be configured to treat and ablate diseased tissue in that region. In one embodiment, the endoscopic ablation system  10  may be employed as a diagnostic instrument to collect a tissue sample using a biopsy device introduced into the tissue treatment region via an endoscope (e.g., the endoscopic ablation system  10 ). In one embodiment, the endoscopic ablation system  10  may be adapted to treat diseased tissue, such as cancers, of the gastrointestinal (GI) tract or esophagus that may be accessed orally. In another embodiment, the endoscopic ablation system  10  may be adapted to treat diseased tissue, such as cancers, of the liver or other organs that may be accessible trans-anally through the colon and/or the abdomen. 
         [0034]    One embodiment of the endoscopic ablation system  10  may be mounted on a flexible endoscope  12  (also referred to as endoscope  12 ), such as the GIF-100 model available from Olympus Corporation. The flexible endoscope  12  includes an endoscope handle  34  and a flexible shaft  32 . The endoscopic ablation system  10  generally comprises one or more therapeutic/diagnostic probe  20 , a plurality of conductors  18 , a handpiece  16  having a switch  62 , and an electrical waveform generator  14 . In one embodiment, the electrical waveform generator  14  may be a high voltage direct current (DC) irreversible electroporation (IRE) generator. The therapeutic/diagnostic probe  20  is located at a distal end of the flexible shaft  32  and the conductors  18  attach to the flexible shaft  32  using a plurality of clips  30 . The therapeutic/diagnostic probe  20  comprises an elongate member attached to an electrical energy delivery device comprising one or more electrical therapy electrodes  28 . In one embodiment, the therapeutic/diagnostic probe  20  extends through a bore in the flexible shaft  32  such as a working channel  36  ( FIG. 2 ). In one embodiment, the therapeutic/diagnostic probe  20  may comprise elongate diagnostic probes  26  attached or joined to the electrodes  28  that extend through the working channel  36 . In another embodiment, the flexible shaft  32  may comprise two working channels  36  and a first diagnostic probe  26  joined to a first electrode  28  that extends through the distal end of a first working channels  36  and a second diagnostic probe  26  joined to a second electrode  28  that extends through the distal end of a second working channel  36 . In one embodiment, the diagnostic probe comprises one or more diagnostic probes  26  attached or joined in any suitable manner to the electrodes  28 . For example, the diagnostic probes  26  may be joined or attached to the electrodes  28  by welding, soldering, brazing or other well known techniques. Many different energy sources may be used for welding, soldering, or brazing such as, for example, a gas flame, an electric arc, a laser, an electron beam, friction, and ultrasound. Thus, in one embodiment, the therapeutic/diagnostic probe  20  may be employed in a diagnostic mode to take a biopsy sample of the diseased tissue using the diagnostic probes  26  and, in one embodiment the therapeutic/diagnostic probe  20  may be employed in a therapeutic mode by treating diseased tissue with electrical current delivered by the electrodes  28 . In other embodiments, the therapeutic/diagnostic probe  20  may be employed in a combination of therapeutic and diagnostic modes. The therapeutic/diagnostic probe  20  may be passed though the one or more working channels  36  located within the flexible shaft  32 . The therapeutic/diagnostic probe  20  is delivered to the tissue treatment region endoscopically and is located on top of the diseased tissue to be electrically treated. Once the therapeutic/diagnostic probe  20  is suitably located by the operator, manual operation of the switch  62  on the handpiece  16  electrically connects or disconnects the electrodes  28  to the electrical waveform generator  14 . Alternatively, the switch  62  may be mounted on, for example, a foot switch (not shown). 
         [0035]    In one embodiment, the electrical waveform generator  14  may be a conventional, bipolar/monopolar electrosurgical generator (ICC200 Erbe Inc.) or an IRE generator such as one of many models commercially available, including Model Number ECM800, available from BTX Boston, Mass. The IRE generator generates electrical waveforms having predetermined frequency, amplitude, and pulse width. The application of these electrical waveforms to the cell membrane causes the cell to die. The IRE electrical waveforms are applied to the cell membranes of diseased tissue in order to kill the diseased cells and ablate the diseased tissue. IRE electrical waveforms suitable to destroy the cells of diseased tissues energy are generally in the form of direct current (DC) electrical pulses delivered at a frequency in the range of 1-20 Hz, amplitude in the range of 100-1000 VDC, and pulse width in the range of 0.01-100 ms. For example, an electrical waveform having amplitude of 500 VDC and pulse duration of 20 ms may be delivered at a pulse repetition rate or frequency of 10 HZ can destroy a reasonably large volume of diseased tissue. Unlike RF ablation systems which require high power and energy input into the tissue to heat and destroy the tissue, IRE requires very little energy input into the tissue, rather the destruction of the tissue is caused by high electric fields. It has been determined that in order to destroy living tissue, the waveforms have to generate an electric field of at least 30,000 V/m in the tissue treatment region. In one embodiment, the IRE generator  14  may generate voltages from about 100-1000 VDC. The IRE generator  14  may generate voltage pulses from 0.01-100 ms. These pulses may be generated at a suitable pulse repetition rate. The electrical current depends on the voltage amplitude, pulse width, pulse repetition rate, and the volume of tissue being treated. In one embodiment, the IRE generator  14  generates 20 ms pulses of 500 VDC amplitude between the electrodes  28 . The embodiments, however, are not limited in this context. 
         [0036]    When using the IRE generator  14  in monopolar mode with two or more electrical therapy electrodes  28 , a grounding pad is not needed on the patient. Because a generator will typically be constructed to operate upon sensing connection of ground pad to the patient when in monopolar mode, it can be useful to provide an impedance circuit to simulate the connection of a ground pad to the patient. Accordingly, when the electrical ablation system  10  is used in monopolar mode without a grounding pad, an impedance circuit can be assembled by one skilled in the art, and electrically connected in series with one of the electrical therapy electrodes  28  that would otherwise be used with a grounding pad attached to a patient during monopolar electrosurgery. Use of an impedance circuit allows use of the IRE generator  14  in monopolar mode without use of a grounding pad attached to the patient. 
         [0037]      FIG. 2  is an enlarged view of one embodiment of the therapeutic/diagnostic probe  20  of one embodiment of the endoscopic ablation system  10  shown in  FIG. 1 . The therapeutic/diagnostic probe  20  extends through the distal end of the flexible shaft  32 . In one embodiment, the therapeutic/diagnostic probe  20  protrudes from the distal end of an internal lumen extending between the proximal and distal ends of the flexible endoscope  12 . In one embodiment, the therapeutic/diagnostic probe  20  may comprise a biopsy device adapted and configured to remove sample tissue using an incisional, core, needle aspiration, or optical biopsy techniques. In one embodiment, the biopsy device comprises one or more diagnostic probes  26 . As previously discussed, the electrical therapy electrodes  28  may be joined or attached to the diagnostic probes  26  in any suitable manner. 
         [0038]    As previously discussed, the electrical therapy electrodes  28  are connected to the diagnostic probes  26  in any known suitable manner and are located in a spaced-apart relationship so as to define a distance D between the electrodes. The distance D is adjustable and can be increased or decreased by rotating one or both of the diagnostic probes  26 . The therapeutic/diagnostic probe  20  are rotatable about a central axis  39 . Thus, the diagnostic probes  26  and the electrodes  28  are rotatable about the central axis  39 . The electrodes  28  may be rotated to increase or decrease the relative distance D between the electrode  28  either to focus the energy in a smaller tissue region or to enlarge the tissue treatment region. In this manner, the operator can surround the diseased tissue such as a cancerous lesion, a polyp, or a tumor. The electrodes  28  are energized with the electrical waveform generator  14  to treat the diseased tissue. The diagnostic probes  26  have a sharp tooth  33  at the distal end and are moveable from the distal end to the proximal end of the flexible shaft  32  capable of slicing a thin section of the tissue to obtain a biopsy sample (shown in more detail below). The diagnostic probes  26  may comprise a bore  35  ( FIGS. 3A , B) at the distal end extending from a proximal end to the distal end of the diagnostic probes  26 . Suction may be applied at the proximal end of the probes to remove a tissue sample before and/or after treatment through the bore  35  ( FIGS. 3A , B) formed through the diagnostic probes  26 . 
         [0039]    The electrical therapy electrodes  28  may be positioned in any orientation relative to the diagnostic probes  26 . The electrodes  28  and the diagnostic probes  26  may have any suitable shape. In the illustrated embodiment, the electrodes  28  may have a generally cuboidal shape and the diagnostic probes  26  may have an elongate cylindrical shape with a sharp tooth  33  and a bore  35  formed therein at the distal end. The electrical conductors  18  are electrically insulated from each other and surrounding structure except for the electrical connections the electrodes  28 . The distal end of the flexible shaft  32  of the flexible endoscope  12  may comprise a light source  40 , a viewing port  38 , and one or more working channels  36 . The viewing port  38  transmits an image within its field of view to an optical device such as a charge coupled device (CCD) camera within the flexible endoscope  12  so that an operator may view the image on a display monitor (not shown). In the embodiment shown in  FIG. 2 , the distal end of flexible shaft  32  is proximal to the electrodes  28  and is within the viewing field of the flexible endoscope  12  to enable the operator to see the diseased tissue to be treated between the electrodes  28 . 
         [0040]      FIG. 3A  is a side view of the distal end of one embodiment of the therapeutic/diagnostic probe  20  comprising a biopsy probe  26  and an electrical therapy electrode  28  assembly.  FIG. 3B  is a sectional view of one embodiment of a therapeutic/diagnostic probe  20  taken along section line  3 B- 3 B showing the geometric relationship between the electrodes  28  and the diagnostic probes  26 . In the embodiment illustrated in  FIGS. 3A , B, the cuboidal electrodes  28 , each have a width “w,” a length “l,” and a thickness or height “h.” The electrodes  28  have parallel, adjacent edges  8  separated by a distance “D.” This geometry of the electrodes  28 , the distance D between them, and the electrical waveform may be used to calculate an ablation index, which has particular significance to the location, size, shape, and depth of ablation achievable, as will be described later. The diagnostic probes  26  may be juxtaposed with the electrodes  28 . In this embodiment, the two cylindrically elongate diagnostic probes  26  have a bore  35  for removing ablated tissue or taking biopsy samples of the tissue by way of suction. The length of the diagnostic probes  26  may extend through the entire length of the flexible endoscope  12 . The conductors  18  are attached to the electrodes  28  in any suitable manner including welding, soldering, or brazing and may employ many different energy sources such as, for example, a gas flame, heat source, an electric arc, a laser, an electron beam, friction, and ultrasound. The electrodes  28  are attached to the diagnostic probes  26  and may be rotated about the central axis  39  in the directions indicated by arrows  31   a  and  31   b.    
         [0041]      FIG. 4  is a sectional view of the lower end of an esophagus  42  and the upper portion of a stomach  54  of a human being. The esophagus  42  has a mucosal layer  46 , a muscular layer  44 , and a region of diseased tissue  48 . The boundary between the mucosal layer  46  of the esophagus  42  and a gastric mucosa  50  of the stomach  54  is a gastro-esophageal junction  52 , which is approximately the location for the lower esophageal sphincter (LES). The LES allows food to enter the stomach  54  while preventing the contents of the stomach  54  from refluxing into the lower esophagus  42  and damaging the mucosal layer  46 . The diseased tissue  48  can develop when chronic reflux is not treated. In one form, the diseased tissue  48  may be, for example, intestinal metaplasia, which is an early stage of Barrett&#39;s esophagus. As can be seen in  FIG. 4 , the esophagus  42  is relatively flaccid and contains numerous folds and irregularities on the interior lining. 
         [0042]      FIG. 5  illustrates the use of one embodiment of the endoscopic ablation system  10  to treat the diseased tissue  48  in the lower esophagus  42 . The operator positions the therapeutic/diagnostic probe  20  using endoscopic visualization so that the diseased tissue  48  to be treated is within the field of view of the flexible endoscope  12 . Once the operator positions the therapeutic/diagnostic probe  20  such that the electrical therapy electrodes  28  are located above the diseased tissue  48 , the operator may energize the electrodes  28  with the electrical waveform generator  14  to destroy the diseased tissue  48  in the tissue treatment region. For example, the electrodes  28  may be energized with an electrical waveform having amplitude of approximately 500 VDC and a pulse width of approximately 20 ms at a frequency of approximately 10 Hz. In this manner, the diseased tissue  48  in the tissue treatment region may be destroyed. This procedure may take very little time and may be repeated to destroy relatively larger portions of the diseased tissue  48 . Suction may be applied to remove the treated tissue sample through the bore  35  formed in the diagnostic probes  26 . 
         [0043]      FIG. 6  illustrates the use of the endoscopic ablation system  10  to treat the diseased tissue  48  in the lower esophagus  42 . As shown in the illustrated embodiment, the electrical therapy electrodes  28  can be rotated about the central axis  39  in the direction indicated by arrows  31   a  and  31   b.  The treated tissue can be sucked into the bore  35  of the biopsy probe  26  by applying suction to thereto. 
         [0044]      FIG. 7  illustrates one embodiment of a necrotic zone  70  defined by the geometry and placement of the electrical therapy electrodes  28 . The energy delivered by the waveform to the electrodes  28  in terms of frequency, amplitude, and pulse width should be suitable to destroy the tissue in the necrotic zone  70 . Based on the location and geometry of the electrodes  28 , and the energy delivered thereto, the necrotic zone  70  in the illustrated embodiment may be approximated generally as a volume of width “wnz,” a thickness “tnz,” and a length “lnz.” Energizing the electrodes  28  destroys the diseased tissue  48  within the necrotic zone  70 . In one embodiment, electrodes  28  with a width “w=0.5 mm,” a length “l=10 mm,” and a thickness “h=0.5 mm” (as shown in  FIGS. 3A , B) and a waveform of approximately 500 VDC, a pulse width of 20 ms, and a frequency of 10 Hz, would define a necrotic zone  70  with dimensions of approximately wnz=6 mm wide, lnz=10 mm long, and hnz=2 mm deep. If a biopsy indicates that the treatment region includes dysplastic or malignant cells, or if the treatment region is larger than the necrotic zone  70 , the process may be repeated until all the diseased tissue  48  is destroyed in the treatment region and clean margins are recorded. In one embodiment, optical biopsy may be used as an alternative to the vacuum diagnostic probes  26  shown in the illustrated embodiments. 
         [0045]      FIG. 8  is a sectional view taken along the longitudinal axis of one embodiment of an endoscopic ablation system  10  shown in  FIG. 1 . The distal portion of the flexible shaft  32  is located inside a rotation tube  22  of the endoscopic ablation system  10 . The pair of electrical conductors  18  pass through a strain relief  66  of a rotation knob  58 . In the illustrated embodiment an external tube  64  may be located over the flexible shaft  32  such that the conductors  18  pass between the external tube  64  and the rotation tube  22 . Each of the conductors  18  connect electrically to the electrical therapy electrodes  28  in the therapeutic/diagnostic probe  20 . The rotation tube  22  rotatably joins the rotation knob  58 . The operator can rotatably orient the electrodes  28 , even after insertion into the esophagus, by remotely rotating the diagnostic probes  26  about the central axis  39  of each of the therapeutic/diagnostic probe  20 . The therapeutic/diagnostic probe  20  is within the field of view of the flexible endoscope  12 , thus enabling the operator to see on a display monitor the tissue that is located between the electrodes  28 . Optionally, in one embodiment, a valve element (not shown) may extend from the distal end of therapeutic/diagnostic probe  20  to prevent tissue or fluids from entering the therapeutic/diagnostic probe  20 . 
         [0046]      FIG. 9  is an end view taken along line  9 - 9  of one embodiment of the therapeutic/diagnostic probe  20  of the endoscopic ablation system  10  shown in  FIG. 8 . The electrical conductors  18  connect to the electrical therapy electrodes  28 . The rotation tube  22  retains the flexible shaft  32 . The inside diameter of the rotation tube  22  is larger than the outer diameter of the flexible endoscope  12  to allow rotation of the rotation tube  22  while holding the flexible endoscope  12  stationary, or vice versa. Each of the therapeutic/diagnostic probe  20  comprising the diagnostic probes  26  attached to the electrodes  28  extend outwardly from the distal end of the flexible shaft  32  through each of the working channels  36 . In this embodiment, the operator may endoscopically view the tissue between the electrodes  28 . The flexible endoscope  12  includes the light source  40 , the viewing port  38 , and the one or more working channels  36 . 
         [0047]      FIG. 10  is a sectional view taken along line  10 - 10  of the rotation tube  22  of the endoscopic ablation system  10  shown in  FIG. 8 . The external tube  64  and the rotation tube  22  assemble and retain the electrical conductors  18  as already described. The light source  40 , the viewing port  38 , and the one or more working channels  36  of the flexible endoscope  12  are shown. 
         [0048]      FIG. 11  shows one embodiment of the distal portion of the endoscopic ablation system  10  shown in  FIG. 1  partially inserted into the esophagus  42  of a patient. A tapered end cover  84  dilates the esophagus  42  as the operator gently inserts the therapeutic/diagnostic probe  20  for positioning near the diseased tissue  48  to be ablated. A flexible coupling  88  flexes as shown, reducing the required insertion force and minimizing trauma (and post-procedural pain). 
         [0049]    The operator may treat the diseased tissue  48  using the embodiment of the endoscopic ablation system  10  comprising the therapeutic/diagnostic probe  20  shown in  FIGS. 1-3 and 5-11  as follows. The operator inserts the flexible shaft  32  of the endoscope  12  into the lower esophagus  42  trans-orally. A rigid support member at the distal end of the endoscope  12  holds the lower esophagus  42  open as the operator uses endoscopic visualization through the therapeutic/diagnostic probe  20  to position the electrical therapy electrodes  28  next to the diseased tissue  48  to be treated. The rigid support member opens and supports a portion of the flaccid, lower esophagus  42  and helps to bring the diseased tissue  48  to be treated into intimate contact with the electrodes  28  and within the field of view of the flexible endoscope  12 . While watching through the viewing port  38 , the operator actuates the switch  62 , electrically connecting the electrodes  28  to the electrical waveform generator  14  through the electrical conductors  18 . Electric current then passes through the portion of the diseased tissue  48  positioned between the electrodes  28  and within the field of view. When the operator observes that the tissue in the field of view has been ablated sufficiently, the operator deactuates the switch  62  to stop the ablation. The operator may reposition the electrodes  28  for subsequent tissue treatment, or may withdraw the therapeutic/diagnostic probe  20  (together with the flexible endoscope  12 ). 
         [0050]      FIG. 12  is a diagram of one embodiment of a control loop  80  for one embodiment of an IRE therapy procedure to treat diseased tissue as described herein. As previously discussed, the IRE therapy may be effective in quickly creating necrosis of live tissue and destroying diseased (e.g., cancerous) tissue in-vivo. Real time information feedback about the size in volume of a necrotic zone may be helpful during an IRE therapy procedure for focal treatment of diseased tissue  48 . 
         [0051]    Prior to an IRE therapy procedure, a patient  82  will have an image of the diseased tissue  48  taken for clinical purposes in an effort to reveal, diagnose, or examine the diseased tissue  48  and to identify its location more precisely. The image information  84  will generally include geometric information about the volume of the diseased tissue  48 . The image information  84  is provided to an image processing module  86  to calculate the volume of the diseased tissue  48  and to display a virtual model of the diseased tissue  48  on a monitor. The image processing module  86  may comprise, for example, image processing software applications such as Comsol Multiphysics available by Comsol, Inc. to receive the image information  84 , extract the geometric information, and determine (e.g., calculate) the voltage required to treat the proper volume and outline of the necrotic zone required to treat the diseased tissue  48 . The image processing module  86  creates a virtual model of a treatment zone necessary to treat the diseased tissue  48 . The image processing module  86  then determines waveform parameters  88  of a suitable electrical waveform necessary to destroy the diseased tissue  48 . The waveform parameters  88  include the frequency, amplitude, and pulse width of the electrical waveform to be generated by the waveform generator  14 . The waveform generator  14  would then generate the suitable electrical waveform to destroy the diseased tissue  48  based on the calculated waveform parameters  88 . 
         [0052]    The image processing module  86  also comprises image processing software applications such as Matlab available by Math Works, Inc. to receive the image information  84  and the virtual model and display an image of the diseased tissue  48  overlaid with an image of the virtual model. The overlaid images enable the operator to determine whether the calculated electrical waveform parameters  88  are suitable for destroying the diseased tissue  48 , whether too strong or too weak. Thus, the IRE waveform parameters  88  may be adjusted such that the virtual model image substantially over-lays the entire diseased tissue image. The calculated parameters  88  are provided to the waveform generator  14  and the diseased tissue may be treated with an electrical waveform  89  based on the calculated parameters  88  as discussed herein. After the diseased tissue  48  is treated with the electrical waveform  89 , a new image of the diseased tissue  48  can be generated to determine the extent or effectiveness of the treatment. The cycle may be repeated as necessary to ablate the diseased tissue  48  as much as possible. 
         [0053]      FIG. 13  illustrates one embodiment of an electrical scalpel  90  for dissecting tissue  92 . In one embodiment, the electrical scalpel  90  may be driven by an IRE waveform previously described. The scalpel  90  comprises a blade  98  that is formed of metal such as hardened and tempered steel (and/or stainless in many applications). The blade  98  is connected to the electrical waveform generator  14  by multiple electrical conductors  96 . The electrical waveform generator  14  may generate an IRE waveform (e.g., 10 Hz frequency, 500 VDC amplitude, and 20 ms pulse). As the blade  98  dissects the tissue  92  along an incision  100 , the electrical waveform generator  14  may be activated or pulsed to create a tissue destruction zone  94  surrounding the blade  98 . Accordingly, as the blade  98  dissects the diseased tissue  92  it generates the tissue destruction zone  94  beyond the incision  100 . This may help to ensure the destruction of any diseased tissue cells left behind. The pulse repetition rate or frequency of the electrical waveform generated by the generator  14  may be selected to provide a continuous zone of tissue destruction  94  as the blade  98  moves through the diseased tissue  92 . In one embodiment, a feedback signal (e.g., audio, visual, or cut-off of electrical power to the blade  98 ) may be provided to the operator to indicate that the scalpel  90  is moving too quickly. 
         [0054]      FIG. 14  is a graphical representation  110  (graph) of electric field strength (along the y-axis) as a function of distance from an electrical therapy electrode  28  under various conductivity environments near the diseased tissue  48 .  FIG. 15  is a close up of the graph  110  shown in  FIG. 14A . In electrical therapy of diseased tissue  48 , the volume of tissue that can be destroyed by an electrical waveform (e.g., the necrotic zone) may be defined by a minimum electric field strength applied to the tissue treatment region. The electric field strength in the tissue treatment region varies throughout the tissue as a function of the applied electrical waveform parameters frequency, amplitude, and pulse width as well as the conductivity of the tissue in the treatment region. When a single electrical therapy electrode  28  is located in a first position in the tissue treatment region of interest and a return pad is placed at a distance relatively far from the first position, an electric field is generated around the electrode  28  when it is energized with a particular electrical waveform. The magnitude of the electric field, however, diminishes rapidly in the radial direction away from the electrode  28 . When two electrodes  28  are placed relatively close together, a larger pattern of tissue can be destroyed. Injecting a fluid having a higher conductivity than the tissue into the tissue treatment region extends the electric field of sufficient strength to destroy the tissue radially outwardly from the electrode  28 . Thus, the addition of a fluid having higher conductivity than the tissue to be treated creates a larger tissue destruction zone by extending the electric field radially outwardly from the electrodes  28 . 
         [0055]    The graph  110  illustrates the electric field strength, along the y-axis, as a function of the radial distance from the electrical therapy electrode  28 . The y-axis is labeled in units of volts/meter (V/m×e 5 ) and the x-axis is labeled in units of mm. The graph  110  illustrates a family of three functions with conductivity as a parameter. A first function  112  illustrates the electric field strength as a function of the radial distance from one of the electrodes  28  with no conductivity plug introduced into the tissue treatment region. A second function  114  illustrates the electric field strength as a function of the radial distance from one of the electrodes  28  with a conductivity plug of 0.2 S/m introduced in the tissue treatment region. A third function  116  illustrates the electric field strength as a function of the radial distance from one of the electrodes  28  with a conductivity plug of 0.5 S/m introduced in the tissue treatment region. As shown in the graph  110 , the peak electric field strength of each of the functions  112 ,  114 ,  116  decreases with increased conductivity in the tissue treatment region in proximity to the electrode  28 . However, the threshold  118  of each of the functions  112 ,  114 ,  116  where the electric field strength drops below the minimum threshold  118  of electric field strength required to destroy tissue becomes wider as the conductivity increases. In other words, increasing the conductivity of the tissue in the tissue treatment region extends the range of an effective electric field to destroy tissue or creates a larger necrotic zone. In one embodiment, the minimum electric field strength threshold  118  is approximately 30,000V/m. 
         [0056]    The devices disclosed herein can be designed to be disposed of after a single use, or they can be designed to be used multiple times. In either case, however, the device can be reconditioned for reuse after at least one use. Reconditioning can include any combination of the steps of disassembly of the device, followed by cleaning or replacement of particular pieces, and subsequent reassembly. In particular, the device can be disassembled, and any number of the particular pieces or parts of the device can be selectively replaced or removed in any combination. Upon cleaning and/or replacement of particular parts, the device can be reassembled for subsequent use either at a reconditioning facility, or by a surgical team immediately prior to a surgical procedure. Those skilled in the art will appreciate that reconditioning of a device can utilize a variety of techniques for disassembly, cleaning/replacement, and reassembly. Use of such techniques, and the resulting reconditioned device, are all within the scope of the present application. 
         [0057]    Preferably, the various embodiments of the invention described herein will be processed before surgery. First, a new or used instrument is obtained and if necessary cleaned. The instrument can then be sterilized. In one sterilization technique, the instrument is placed in a closed and sealed container, such as a plastic or TYVEK bag. The container and instrument are then placed in a field of radiation that can penetrate the container, such as gamma radiation, x-rays, or high-energy electrons. The radiation kills bacteria on the instrument and in the container. The sterilized instrument can then be stored in the sterile container. The sealed container keeps the instrument sterile until it is opened in the medical facility. 
         [0058]    It is preferred that the device is sterilized. This can be done by any number of ways known to those skilled in the art including beta or gamma radiation, ethylene oxide, steam. 
         [0059]    Although the various embodiments of the invention have been described herein in connection with certain disclosed embodiments, many modifications and variations to those embodiments may be implemented. For example, different types of end effectors may be employed. Also, where materials are disclosed for certain components, other materials may be used. The foregoing description and following claims are intended to cover all such modification and variations. 
         [0060]    Any patent, publication, or other disclosure material, in whole or in part, that is said to be incorporated by reference herein is incorporated herein only to the extent that the incorporated materials does not conflict with existing definitions, statements, or other disclosure material set forth in this disclosure. As such, and to the extent necessary, the disclosure as explicitly set forth herein supersedes any conflicting material incorporated herein by reference. Any material, or portion thereof, that is said to be incorporated by reference herein, but which conflicts with existing definitions, statements, or other disclosure material set forth herein will only be incorporated to the extent that no conflict arises between that incorporated material and the existing disclosure material.