Abstract:
A focal ablation assembly, used with an endoscope comprising an endoscopic tube, comprises a cryogenic catheter, a balloon and a reinforcing element. The cryogenic catheter is placeable within the endoscopic tube channel and has a distal end placeable at the distal end of the endoscopic tube. The balloon is mountable to the catheter distal end and extends distally of both of the distal ends. The reinforcing element at least partially defines the shape of the balloon in the expanded state. The balloon defines a balloon volume when expanded and has a thermally conductive therapeutic region which provides effectively no thermal insulation. In some examples the focal ablation assembly comprises a delivery catheter extending along the channel with a distal portion fluidly coupled to the balloon interior, whereby refrigerant can be introduced into the balloon interior and towards the therapeutic region by the delivery catheter.

Description:
CROSS-REFERENCE TO OTHER APPLICATIONS 
       [0001]    This application is related to the following US patent application publication: US 2010/0130970 A1 (attorney docket WILL 1002-2). 
     
    
     FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
       [0002]    None. 
       BACKGROUND OF THE INVENTION 
       [0003]    Throughout the GI tract in the human body there are focal lesions of unwanted or unhealthy tissue that physicians desire to remove or ablate in situ. Examples of these lesions include ‘islands’ of intestinal metaplasia and dysplasia in the esophagus or ‘flat’ polyps in the colon. Removal of these tissues through techniques such as Endoscopic Mucosal Resection (EMR) may create unwanted complications such as bleeding and current ablative modalities such as Argon Plasma Coagulation (APC) and Radio Frequency Ablation (RFA) suffer from a variety of drawbacks. Furthermore, existing cryoablation technologies, which spray the cryogen directly onto the body lumen do not adequately allow control of the energy dosage. 
       BRIEF SUMMARY OF THE INVENTION 
       [0004]    An example of a focal ablation assembly is used with an endoscope comprising an endoscopic tube having proximal and distal ends and defining a channel extending between the proximal and distal ends. The focal ablation assembly comprises a cryogenic catheter, a balloon and a reinforcing element. The cryogenic catheter is placeable within the channel. The cryogenic catheter defines a catheter lumen and has a distal end placeable at the distal end of the endoscopic tube. The balloon is mountable to at least one of the distal end of the endoscopic tube and the distal end of the catheter. The balloon extends distally of both of the distal ends of the endoscopic tube and the cryogenic catheter. The reinforcing element at least partially defines the shape of the balloon in the expanded state. The balloon defines a balloon volume when in the expanded state. The balloon comprises a thermally conductive therapeutic region, the thermally conductive therapeutic region providing effectively no thermal insulation. In some examples the therapeutic region comprises a flexible, tissue-conformable therapeutic region. In some examples the thermal conductivity of the balloon is greater at the therapeutic region than at a portion of the remainder of the balloon. In some examples the focal ablation assembly comprises a delivery catheter extending along the channel with a distal portion fluidly coupled to the balloon interior, whereby refrigerant can be introduced into the balloon interior and towards the therapeutic region by the delivery catheter. In some examples the reinforcing elements are formed integrally with the balloon. In some examples the reinforcing elements comprise at least two spaced-apart support wires extending at least part way along the balloon interior. In some examples the reinforcing elements cause the balloon to have a flattened cross-sectional shape in the expanded state. 
         [0005]    An example of a focal ablation system comprises an endoscope and a focal ablation assembly. The endoscope comprises an endoscopic tube having proximal and distal ends and defines a channel extending between the proximal and distal ends. The focal ablation assembly comprises a cryogenic catheter, a balloon, and a reinforcing element. The cryogenic catheter is located within the channel and defines a catheter lumen. The cryogenic catheter has a distal end at the distal end of the endoscopic tube. The balloon is mounted to the distal end of the catheter with the balloon extending distally of both of the distal ends of the endoscopic tube and the cryogenic catheter. The balloon is placeable in collapsed and expanded states and has a balloon interior. The reinforcing element at least partially defines the shape of the balloon in the expanded state. The balloon defines a balloon volume when in the expanded state. The balloon comprises a flexible, tissue-conformable, thermally conductive therapeutic region, the thermally conductive therapeutic region providing effectively no thermal insulation. Some examples of the focal ablation system include a delivery catheter extending along the channel and having a distal portion fluidly coupled to the balloon interior, whereby refrigerant can be introduced into the balloon interior and towards the therapeutic region by the refrigerant delivery catheter. Some examples of the focal ablation system include an exhaust lumen within at least one of (1) the channel of the endoscopic tube, and (2) the catheter lumen. 
         [0006]    Other features, aspects and advantages of the present invention can be seen on review the figures, the detailed description, and the claims which follow. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0007]      FIGS. 1A and 1B  are overall views showing focal ablation systems made according to the invention. 
           [0008]      FIGS. 1A-11  are directed to a first type of a focal ablation system according to a first aspect of the invention. 
           [0009]      FIG. 2  is a simplified enlarged cross-sectional view of the distal end of one example of the system of  FIG. 1A  showing a cryogenic catheter passing through the channel of an endoscopic tube with a cap mounted to the distal end of the endoscopic tube, the cap having a thermally conductive therapeutic region located at the distal end of the cap. 
           [0010]      FIG. 3  is a view similar to that of  FIG. 2  of an alternative example of the system of  FIG. 1A  in which the therapeutic region is along a sidewall of the cap. 
           [0011]      FIG. 4  is a view similar to that of  FIG. 2  wherein the cap is mounted to the distal end of the cryogenic catheter instead of the endoscopic tube as shown in  FIG. 1B . 
           [0012]      FIGS. 5A-5C  are simplified cross-sectional views of examples of three different caps in which the cross-sectional area of the therapeutic region at the distal end of each cap is different while the cross-sectional area of the endoscopic tube to which it is mounted remains the same. 
           [0013]      FIG. 6  illustrates an example in which the therapeutic region has a convex outer surface. 
           [0014]      FIGS. 7A ,  8 A and  9 A are simplified end views showing caps having round, generally oval and rectangular cross-sectional shapes, respectively, each mounted to the distal end of an endoscope, each Fig. illustrating a conventional endoscope having, in this example, a camera, two lights for illumination and a working channel. 
           [0015]      FIGS. 7B ,  8 B and  9 B show the caps of  FIGS. 7A ,  8 A and  9 A having distal ends oriented perpendicular to the centerlines of the respective caps. 
           [0016]      FIGS. 7C ,  8 C and  9 C show the caps of  FIGS. 7A ,  8 A and  9 A having distal ends oriented obliquely to the centerlines of the respective caps. 
           [0017]      FIG. 10  shows an example of a cap similar to the cap of  FIG. 2  but in which the cap has an extension defining an exhaust lumen coaxial with the endoscopic tube. 
           [0018]      FIGS. 11-15  show balloon-type of focal ablation systems according to a second aspect of the invention. 
           [0019]      FIG. 11  shows an example of a balloon type focal ablation system in which an elastomeric balloon is mounted to the distal end of the cryogenic catheter and expands within the cap, a portion of the balloon forming a barrier to the refrigerant along the therapeutic region at the distal end of the cap. 
           [0020]      FIGS. 12 and 12A  are simplified side and end cross-sectional views of a balloon type focal ablation system in which a balloon type focal ablation assembly is used with an endoscopic tube, the balloon being mounted to the distal end of a cryogenic catheter, the cryogenic catheter passing through the channel of the endoscopic tube, the therapeutic region being along a sidewall of the balloon.  FIG. 12A  shows the use of reinforcing elements within the balloon to cause the balloon to have a flattened or oval cross-sectional shape to better conform to the sidewall of the body lumen. 
           [0021]      FIGS. 13 and 13A  are simplified side and end cross-sectional views of a focal ablation balloon and reinforcing elements similar to those of  FIGS. 12 and 12A . 
           [0022]      FIG. 14  illustrates another example of a balloon type focal ablation system in which the distal end of a reinforcing element extends through the delivery catheter and is secured to the distal portion of the balloon. 
           [0023]      FIG. 15  shows a further example of a balloon type focal ablation system comprising a balloon type cap. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0024]    The following description will typically be with reference to specific structural embodiments and methods. It is to be understood that there is no intention to limit the invention to the specifically disclosed embodiments and methods but that the invention may be practiced using other features, elements, methods and embodiments. Preferred embodiments are described to illustrate the present invention, not to limit its scope, which is defined by the claims. Those of ordinary skill in the art will recognize a variety of equivalent variations on the description that follows. Like elements in various embodiments are commonly referred to with like reference numerals. 
         [0025]    The control of three primary factors is necessary for repeatable cryoablation via evaporative cooling. These factors are evaporation temperature of the cryogen, the mass flow rate of the cryogen/surface area, and the amount of time that the cryogen is applied. The present invention directly addresses two of these factors. (1) Evaporation temperature of the cryogen is set by controlling the evaporation pressure. The evaporation pressure can be controlled by appropriately sizing the cryogenic refrigerant delivery and exhaust lumens. (2) The mass flow rate/surface area can be controlled by appropriately sizing the cryogenic refrigerant delivery lumen (to control mass flow rate) and defining a fixed treatment area either by physically defining a treatment area or by controlling distribution of the cryogen delivery onto a treatment surface. 
         [0026]      FIG. 1A  is an overall view showing a generalized example of a focal ablation system  10  including broadly an endoscope  12  and a focal ablation assembly  14 . Endoscope  12  includes an endoscopic tube  16  having an accessory channel port  18  at a proximal end  20  of endoscopic tube  16  and a cap  22  at the distal end  24  of endoscopic tube  16 . Endoscope  12  may be a conventional endoscope such as Olympus GIF-140 or GIF-Q160Z, that connects to an image processor  19 , which then displays the image on monitor  21 .  FIG. 1B  is similar to  FIG. 1A  but shows cap  22  mounted to the distal end  34  of cryogenic catheter  26  instead of endoscopic tube  16 . 
         [0027]      FIGS. 2-12  are directed to a first type of a focal ablation system  10  according to a first aspect of the invention. Focal ablation assembly  14 , see  FIGS. 1 and 2 , includes a cap  22  mounted to the distal end  24  of an endoscopic tube  16  and a cryogenic catheter  26  passing through the channel  28  of endoscopic tube  16 . Focal ablation assembly  14  also includes a cryoablation controller  25  at the proximal end of  27  of cryogenic catheter  26 . In some examples, described below with reference to  FIGS. 1B and 4 , cap  22  can be mounted to the distal end  34  of cryogenic catheter  26 . Cap  22  in  FIG. 2  has a generally cylindrical cross-sectional shape and defines a centerline  30 . Cap  22  has a distal end  32  extending distally of the distal end  24  of endoscopic tube  16  and the distal end  34  of cryogenic catheter  26 . In this example cap  22  is oriented obliquely to centerline  30  to facilitate tissue apposition. Cryogenic catheter  26  defines a catheter lumen  29  through which a delivery catheter  31  passes. As is discussed in more detail below, distal end  32  of cap  22  will be placed against tissue at the target site to be treated. 
         [0028]    Cap  22  is preferably of a clear, semi-rigid, soft, flexible material, or a combination of materials, such as a polymer material, so to substantially maintain its shape during use while not causing tissue trauma. Examples of the material for  22  include silicone, polyurethane, polyvinyl chloride, and C-Flex®, a thermoplastic elastomer, specifically styrene-ethylene-butylene modified block copolymer with silicone oil. Cap  22  may be manufactured by, for example, injection molding, casting, or thermoforming. Distal end  32  of cap  22  defines a thermally conductive therapeutic region  36  having a typical cross-sectional area of 0.5 cm 2  to 3.0 cm 2 . In this example therapeutic region  36  is covered by a cover  38  of a thin transparent polymer, such as polyurethane having a thickness of typically less than 0.05 mm (0.002 inch). In this way the liquid refrigerant  40  passing through the delivery lumen of delivery catheter  31  and out through the exit opening  41  of delivery catheter  31  does not contact tissue outside the target site but rather heat is removed from the tissue at the target site as the liquid refrigerant evaporates while in contact with cover  38 . Although polyurethane may not be considered to be highly thermally conductive, the thinness of cover  38  allows cover  38  to provide effectively no thermal insulation between the evaporating liquid refrigerant and the target tissue. In addition, it is preferable that cover  38  be transparent or at least translucent so that the physician can see what is happening to the tissue at the target site. The selection of the size of therapeutic region  36  is typically chosen according to the size of the treatment site or the desired mass flow rate/surface area for refrigerant  40 , or both. Evaporated refrigerant  42  passes out of cap volume  39  through catheter lumen  29  between delivery catheter  31  and the inner wall of cryogenic catheter  26 . 
         [0029]    Cover  38  is stated to provide effectively no thermal insulation between the evaporating liquid refrigerant in the target tissue. In this application the phrase effectively no thermal insulation is meant to mean that tissue necrosis can occur at the target site upon the application of a cryogenically ablative liquid refrigerant, such as nitrous oxide (N 2 O), to the surface of cover  38 . 
         [0030]    Cryogenic catheter  26  may be sized appropriately for introduction through, for example, 2.0 mm, 2.8 mm or 3.7 mm diameter instrument channels  28 . Cryogenic catheter  26  may be constructed from materials such as PEBAX or nylon. Delivery catheter  31  may be constructed from a rigid polymer such as polyimide or a metal such as stainless steel, sufficient to withstand internal pressure approaching 1000 psig. The diameter of delivery lumen  44  defined by delivery catheter  31  is typically in the range of 0.15 mm (0.006 inch) to 0.30 mm (0.012 inch). The diameter of delivery lumen  44  can be chosen according to the desired mass flow rate/surface area for refrigerant  40  contacting therapeutic region  36 . 
         [0031]      FIG. 3  is a view similar to that of  FIG. 2  of an alternative example of the focal ablation system  10  of  FIG. 1  in which the therapeutic region  36  is along a sidewall  35  of the cap. Delivery catheter  31  extends completely through cap volume  39  and is secured to a distal end of cap  22 . Delivery catheter  31  has a laterally oriented exit opening  41  positioned opposite the therapeutic region  36  along sidewall  46  of cap  22 . This feature permits liquid refrigerant  40  to be directed against sidewall  46  at therapeutic region  36  so the target tissue at the target treatment site  78  against which therapeutic region  36  is pressing, see  FIG. 12 , can be thermally ablated due to the low temperature of the liquid refrigerant. 
         [0032]      FIG. 4  is a view similar to that of  FIG. 2  wherein the cap  22  is mounted to the distal end  34  of the cryogenic catheter  26  instead of the endoscopic tube  16 . See also  FIG. 1B . 
         [0033]      FIGS. 5A-5C  are simplified cross-sectional views of examples of three different caps  22  in which the cross-sectional area  48  of the therapeutic region  36  at the distal end  32  of each cap  22  is different while the cross-sectional area  50  of the endoscopic tube  16  to which it is mounted remains the same. This concept is used to allow the physician to choose the appropriately sized cap  22  according to the size of the target site, or the mass flow rate/surface area of refrigerant  40 , or both. 
         [0034]      FIG. 6  illustrates an example in which the therapeutic region  36  has a convex outer surface  52 . This configuration may be useful to improve the amount of contact between the therapeutic surface of the cap and the target tissue.  FIGS. 7A ,  8 A and  9 A are simplified end views showing caps  22  having round, generally oval and rectangular cross-sectional shapes, respectively. Each cap  22  is mounted to the distal end  24  of an endoscopic tube  16 . Each figure illustrates a conventional endoscope  12  having, in this example, a camera  53 , two lights  54  for illumination and a working channel  28 . 
         [0035]      FIGS. 7B ,  8 B and  9 B show the caps  22  of  FIGS. 7A ,  8 A and  9 A having distal ends  32  oriented perpendicular to the centerlines  30  of the respective caps.  FIGS. 7C ,  8 C and  9 C show the caps  22  of  FIGS. 7A ,  8 A and  9 A having distal ends  32  oriented obliquely to the centerlines  30  of the respective caps. 
         [0036]      FIG. 10  shows an example of cap  22  similar to the cap  22  of  FIG. 2  but in which an exhaust lumen  56  is defined by a coaxial extension  58  of cap  22 . Extension  58  will lie generally parallel to the endoscopic tube  16 . This permits and a larger cross-sectional area for the exhaust lumen than would be typically available if the exhaust lumen was defined by an accessory channel of endoscopic tube  16 . Exhaust lumen  56  is typically in the range of 2-5 mm in diameter. The cross-sectional areas provided by catheter lumen  29  when used as exhaust lumens in the above examples are typically of a similar size. 
         [0037]      FIG. 11  shows another example in which an elastomeric balloon  60  is mounted to the distal end  34  of the cryogenic catheter  26 . Balloon  60  expands within the cap volume  39  of cap  22  with a portion  62  of the balloon forming the cover  38  along the therapeutic region  36  at the distal end  32  of the cap. A vent hole  63  is formed in the sidewall  35  of cap  22  to facilitate the expansion of balloon  60 . 
         [0038]    In use, the physician will typically select a cap  22  having the appropriate size and shape for the particular target treatment site  78 . The size of therapeutic region  36  may also be chosen according to the desired mass flow rate/surface area for refrigerant  40 . Assuming the focal ablation system  10  of  FIG. 2  is being used, cap  22  can be installed on the distal end  24  of endoscopic tube  16 . Cryogenic catheter  26 , typically with delivery catheter  31  therein, can be placed through accessory port  18  of the endoscope  12  and passes through channel  28  of the endoscopic tube  16  until the distal end  34  of cryogenic catheter  26  is at cap volume  39 . Note that the installation of cap  16  could occur after positioning cryogenic catheter  26  within endoscope  12 . The distal portion of focal ablation system  10  is placed in the patient so that region  36  is properly positioned at the target treatment site  78 . The refrigerant from cryoablation controller  25  is then directed through delivery catheter  31  and against cover  38  at to the target treatment site  78 . The evaporation of the refrigerant on cover  38  lowers the temperature of the tissue at the target treatment site enough to cause necrosis of the tissue. The evaporated refrigerant  42  passes out of cap volume  39  through catheter lumen  29 . 
         [0039]      FIGS. 12-15  show balloon type of focal ablation systems, somewhat different from the focal ablation system of  FIGS. 1-11 , according to a second aspect of the invention. 
         [0040]      FIGS. 12 and 12A  are simplified side and end cross-sectional views of a balloon type focal ablation system  70  in which a balloon type focal ablation assembly  72  is used with an endoscopic tube  16  of an endoscope  12 . A balloon  74  is mounted to the distal end  34  of cryogenic catheter  26 . The cryogenic catheter  26  extends through the channel  28  of endoscopic tube  16 . The therapeutic region  36  is along a sidewall  76  of balloon  74 . In this example cryogenic catheter  26  has a dogleg shape distal portion to facilitate placement of therapeutic region  36  along sidewall  76  and against a target treatment site  78  of the body structure  80 . Delivery catheter  82  passes through lumen  29  with its distal end  84  secured to the distal end  86  of balloon  74 . Delivery catheter  82  has, in this example, a number of laterally directed exit openings  41  acting as delivery ports to direct liquid refrigerant  40  into the interior  85  of balloon  74  and against sidewall  76  of balloon  74  at target site  78 . The size, number and positions of openings  41  can be chosen according to the size of the target treatment site  78  and desired mass flow rate/surface area for refrigerant  40 .  FIG. 12A  shows the use of reinforcing elements  88 , such as nitinol support wires, within the balloon  74  to cause the balloon to have a flattened or oval cross-sectional shape to better conform to the shape of the body structure  80 . The use of reinforcing elements  88  also helps to maintain balloon  74  in direct contact with the body structure during the procedure. 
         [0041]      FIGS. 13 and 13A  are simplified side and end cross-sectional views of a focal ablation balloon  74  and reinforcing elements  88  similar to those of  FIGS. 12 and 12A . 
         [0042]      FIG. 14  illustrates another example of a balloon type focal ablation system  70  in which the distal end of the reinforcing element  88  extends through the delivery catheter  31 . The distal end  90  of reinforcing element  88  is secured to the central portion of the working region  36  of balloon  74  in the following manner. Balloon  74  has a stem portion  92  at the center of therapeutic, working region  36  extending inwardly into the volume  93  defined by the balloon. A thermally conductive filler material  94  is used to secure distal end  90  of reinforcing element  88  to stem portion  92 . As indicated by liquid refrigerant arrows  40 , liquid refrigerant is directed toward the center of working region  36  surrounding stem portion  92 . 
         [0043]      FIG. 15  shows an example of a balloon type focal ablation system comprising a balloon type cap  98 , which is not generally rigid as caps  22  in the examples above  FIGS. 1-11 . Rather, cap  98  is typically made of one or more materials similar to those used with balloon  74  and includes reinforcing elements  88 , not shown in  FIG. 15 , which may be made of, for example, a metal, such as nitinol, or of the same material as the rest of cap  98 . Cap  98  also includes a cover  38 , typically made of a thin film of silicone, polyurethane, or PET. As with the balloon type focal ablation systems  70  of  FIGS. 12-14 , the full expansion of cap  98  is typically the result of reinforcing elements  88  and the internal pressure created by the vaporization of refrigerant  40  and expansion due to the creation of exhaust gas  42 . 
         [0044]    In the use of the focal ablation system  70  of  FIGS. 12-13A , the physician will typically select a focal ablation assembly  72  including a balloon  74  having the appropriate size and shape for the particular target treatment site  78 . Cryogenic catheter  26 , typically with delivery catheter  82  therein and the balloon  74  at the distal end  34 , can be placed through accessory port  18  of the endoscope  12  and pass through channel  28  of the endoscopic tube  16  until sidewall  76  of balloon  74  is adjacent to therapeutic region  36  of body structure  80 . The refrigerant  40  from cryoablation controller  25  is then directed through delivery catheter  82  and against balloon sidewall  76  at to the target treatment site  78 . The evaporation of the refrigerant on sidewall  76  of balloon  74  lowers the temperature of the tissue at the target treatment site  78  enough to cause necrosis of the target tissue. The evaporated refrigerant  42  passes out of the interior of balloon  74  through catheter lumen  29 . The use of the examples of  FIGS. 14 and 15  are carried out in similar manners with the working region  36  positioned at target treatment site  78   
         [0045]    The above descriptions may have used terms such as above, below, top, bottom, over, under, et cetera. These terms may be used in the description and claims to aid understanding of the invention and not used in a limiting sense. 
         [0046]    While the present invention is disclosed by reference to the preferred embodiments and examples detailed above, it is to be understood that these examples are intended in an illustrative rather than in a limiting sense. It is contemplated that modifications and combinations will occur to those skilled in the art, which modifications and combinations will be within the spirit of the invention and the scope of the following claims. For example, cryogenic catheter  26  may also contain features related to measuring the performance of the system for either safety or efficacy reasons. Examples of these features include a pressure sensing lumen for monitoring pressure in the volumes  39 ,  93 , and a temperature sensing device (e.g. thermistor or thermocouple) for monitoring temperature in the cap  22 , especially at working region  36 . 
         [0047]    Any and all patents, patent applications and printed publications referred to above are incorporated by reference.