Abstract:
The present invention relates generally to inducing ischemia and, more particularly, to a method of inducing ischemia via the introduction of a flowable thermopolymer into a target vessel or structure which, after injection, will cool and solidify to obstruct or occlude the vessel or structure. This method of inducing ischemia is particularly suited for the treatment of cancer, by cutting off blood supply to a tumor to facilitate its removal, as well as removing organs as method of treatment or for transplant and/or draining and subsequent reduction and isolation of an organ for removal or for an organ to maintain its contents for removal.

Description:
CROSS REFERENCES TO RELATED APPLICATIONS  
       [0001]     The present application is a nonprovisional patent application claiming benefit under 35 U.S.C. § 119(e) from U.S. Provisional Application Ser. No. 60/515,248, filed on Oct. 28, 2003, the entire contents of which are hereby expressly incorporated by reference into this disclosure as if set forth fully herein. 
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     I. Field of the Invention  
         [0003]     The present invention relates generally to inducing ischemia and, more particularly, to a method of inducing ischemia via the introduction of a flowable thermopolymer into a target vessel or structure which, after injection, will cool and solidify to obstruct or occlude the vessel or structure. This method of inducing ischemia is particularly suited for the treatment of cancer, by cutting off blood supply to a tumor to facilitate its removal, as well as removing organs as method of treatment or for transplant and/or draining and subsequent reduction and isolation of an organ for removal or for an organ to maintain its contents for removal.  
         [0004]     II. Discussion of the Prior Art  
         [0005]     Cancer is a disease that claims the lives of millions of people worldwide. Although there are treatments for the disease, to date there is no cure. Most treatment options are incredibly unpleasant for the patient, and none of them can predict successful recovery with any degree of certainty. Furthermore, many treatment options have debilitating side effects that can affect the lives of cancer patients and their families for the rest of their lives.  
         [0006]     All organs, limbs, and tumors rely on a nutrient supply to sustain life and maintain functionality. The greater the metabolic activity of a structure, the more nutrients are required to remain viable. Active or highly aggressive tumors require a rich blood supply in order for the tumor to proliferate.  
         [0007]     Much of the contemporary treatment of cancer addresses the cellular production or blood supply. Presently the most-utilized treatments for cancer include surgery, radiation, and chemotherapy. In addition, many alternative or experimental treatments are also available, including immunotherapy, hyperthermia, radio frequency ablation, hormonal therapy, angiogenesis inhibitors, photodynamic therapy, and vaccine therapy.  
         [0008]     Each of the primary cancer treatments is highly invasive to the human body, but each in a different way. Removal of tumors via surgery is the most physically invasive technique, yet it potentially carries the lowest degree of damage from side effects. In this treatment, the tumor is physically removed from the body through mechanical processes. Surgical removal can be effective for small tumors, but often it is not possible to extract the entire tumor, and the end result is that cancer remains in the patient. Even if the entire tumor can be removed, doctors must also remove significant portions of healthy tissue and lymph nodes along with the tumor, causing damage to the body.  
         [0009]     Radiation therapy, or radiotherapy, is a treatment method in which high-energy rays are used to treat the cancer cells. Radiation is often used in conjunction with surgical treatment, either pre-surgery to shrink the tumor to allow for easier removal, or post-surgery to remove any remaining cancer cells from the tissue. Radiotherapy does have serious, though mostly temporary, side effects. For instance, patients may experience fatigue, hair loss, skin discoloration, and a decrease in infection-fighting white blood cells.  
         [0010]     The third conventional method of treating cancer is chemotherapy, in which anticancer drugs are administered in a number of ways, including intravenously through a catheter, intrathecally (into the cerebral spinal fluid) through a needle placed in the spine, or by a heavy dosage of pills. The chemicals once introduced are intended to kill the cancer cells. However, chemotherapy also has side effects that are very similar to, if not more severe than, radiotherapy. For example, patients may experience fatigue, hair loss, nausea, vomiting, and general painful discomfort. More serious side effects include permanent infertility and cessation of the menstrual cycle in women. Unlike radiation, chemotherapy is systemic in nature and therefore exposes the entire body to chemicals, increasing the danger of side effects.  
         [0011]     In order to increase the effectiveness and decrease the discomfort associated with the conventional treatments discussed above, many alternative and experimental treatments have emerged in recent years. One such treatment is immunotherapy, in which the body&#39;s immune response is increased in order to fight disease or protect from the harmful side effects of other treatments. Some types of immunotherapy include herbal remedies, monoclonal antibodies, interferons, interleukin-2, and colony stimulating factors. Another type of immunotherapy is the use of cancer vaccines. Ordinarily vaccines are used as preventative treatment, administered prior to contraction of a disease in order to prepare the immune system to rapidly fight the disease. However, cancer vaccines are therapeutic in nature: instead of preparing the body to fight future cancer, they aid the body&#39;s immune system in fighting existing cancer. Immunotherapy as a primary treatment for cancer itself if ineffective at best, and as a result it is used primarily a means to combat side effects of more conventional treatments.  
         [0012]     Another method of treating cancer is hyperthermia, or heating the malignancy to its lethal capacity, heat-killing the tumor. The idea is that since cancer cells have a higher temperature than normal healthy cells, they will reach the lethal temperature for cells faster than the surrounding tissue. However, to date the conventional methods of heating are inadequate because they primarily use external sources of heat and thus cannot reach deep-rooted tumors without creating a toxic temperature gradient within the healthy tissue surrounding the cancer.  
         [0013]     An experimental derivative of the hyperthermia treatment currently in development is Intracellular Hyperthermia Therapy (ICHT). The idea behind ICHT is that if the cancer cells could be heated from the inside, then the damage to surrounding tissue from hyperthermia would be minimized. The suggested method is to introduce an “uncoupling agent” into the bloodstream, which would then infiltrate cells and boost their metabolism on the order of four-fold. Cancer cells, with a much higher metabolism, would be pushed beyond their lethal limit, while normal cells would in theory be unaffected. However, the problem with this treatment is that it still has some effect on normal cells. Specifically, the effect of increased metabolism on normal cells is unknown, and may turn out to be harmful.  
         [0014]     Another relatively new cancer treatment is radio frequency ablation (RFA), in which RF energy is deposited directly into the tumor by a probe. The energy heats the cells beyond their fatal temperature, destroying them. Although still experimental in nature and primarily used for treating liver cancer, this treatment is not without problems. First, the treatment can be extremely painful for the patient, and various forms of sedation are recommended, ranging from conscious sedation to general anesthesia. Secondly, in order to increase the likelihood of success, a zone of normal cells surrounding the tumor must also be killed. Thirdly, tumors located near major arteries cannot be killed completely since the arteries will siphon some of the heat away from the tumor.  
         [0015]     Hormone therapy is an alternative treatment in which cancer cells are starved of the hormones that they need to grow. This can be accomplished either through the administration of hormone-suppressing drugs or surgery to remove a hormone-producing organ. In addition to side effects that are similar to chemotherapy, hormone therapy is only effective against certain types of cancers.  
         [0016]     The use of angiogenesis inhibitors is currently under investigation. The idea behind this type of treatment is to arrest the formation of new blood vessels that provide nutrient-rich blood to the tumors. If such formation can be stopped, then the cancer cells will essentially die from malnutrition. However, the primary drawback to this treatment is that it is still highly experimental, and the effectiveness in fighting cancer is not yet known.  
         [0017]     Yet another type of alternative cancer treatment is photodynamic therapy (also called PDT, phototherapy, photochemotherapy, or photoradiation therapy). PDT is based on the use of photosensitizing agents that can kill one-celled organisms when exposed to a certain type of light. In this treatment, a photosensitizing agent is introduced into the bloodstream and absorbed by cells all over the body, including the target tumor. Since the agent will remain in cancer cells longer than in healthy cells, treatment is delayed for a period of time after introduction of the agent. The tumor is then treated with a laser, activating the photosensitizing agent and causing the production of an active form of oxygen, which will kill the cells. However, many problems are associated with this treatment. First, there is the aforementioned timing problem, and more specifically picking the right time to be most effective. Secondly, the patient&#39;s eyes and skin remain ultra-sensitive to light for at least a period of six weeks. Finally, since the lasers used cannot pass through more than three centimeters of tissue, PDT is not effective against deeper seeded tumors.  
         [0018]     In addition to the specific problems with each treatment discussed above, the central disadvantage to many of these cancer treatments is that it is difficult to isolate the tumors and apply the treatment method only to the target area. As a result, many healthy cells are destroyed along with the tumor. If the treatment is systemic in nature, this can cause a multiplicity of problems all over the body. Similarly, localized treatments can damage significant portions of the body surrounding the tumor.  
         [0019]     Furthermore, treatments involving introduction of foreign elements not accepted by the body—such as chemicals, radiation, or excessive heat—can cause uncomfortable, painful, or even debilitating side effects that may be more than temporary in nature.  
         [0020]     The present invention is directed at overcoming, or at least improving upon, the disadvantages of the prior art.  
       SUMMARY OF THE INVENTION  
       [0021]     The present invention accomplishes the above-identified problems by providing a method of treating cancer using a thermopolymer composition to block arterioles feeding the tumor and induce ischemia, thereby killing the cancer cells. Prior to injection, the thermopolymer material is heated to a temperature sufficient to create a flowable form, whereby it may then be injected into the body. After injection into the arterioles, the material will cool to body temperature and solidify, creating an artificial barrier.  
         [0022]     According to one broad aspect of the present invention, this method of treating cancer comprises a nonreactive thermopolymer composition capable of injection in flowable form and an injection apparatus. It is contemplated that the injection apparatus may itself be able to heat the thermopolymer to flowable form.  
         [0023]     The thermopolymer composition contains the thermopolymer matrix and a dispersion compound. The thermopolymer matrix may include any number of suitable materials capable of being heated to flowable form and injected into an artery, filling the artery and solidifying upon cooling to body temperature in order to form a barrier. The thermopolymer must not react negatively with the body. By way of example only, the thermopolymer matrix may include bone wax, paraffin, gutta percha, balata, polyisoprene and/or any mixture of bone wax, paraffin, gutta percha, balata and/or polyisoprene.  
         [0024]     The dispersion compound may include any number of compositions having suitable mechanical, chemical, radiopacity, anti-microbial and/or anti-inflammatory characteristics. By way of example only, the dispersion compound may include, but is not necessarily limited to, titanium, crystalline particles, gold (in any form) and/or and combination of titanium, crystalline particles, and/or gold.  
         [0025]     The injection device may include any number of mechanisms capable of injecting molten thermopolymer into the body. By way of example only, the injection device may include an injection gun or simple syringe. In a preferred embodiment, the injection gun would be capable of heating the thermopolymer to the desired temperature in order to facilitate dispersion in a molten form. The preferred injection gun would also be able to maintain the temperature of the thermopolymer composition so as to maintain molten consistency throughout application. The preferred embodiment would also contain a specialized injection needle to facilitate optimal dispersion of the thermopolymer compound. In an alternative embodiment, the thermopolymer composition would be heated using an independent device such as a hot pot, open flame, or microwave, and then transferred to a syringe for injection.  
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0026]     Many advantages of the present invention will be apparent to those skilled in the art with a reading of this specification in conjunction with the attached drawings, wherein like reference numerals are applied to like elements and wherein:  
         [0027]      FIG. 1  is a flow chart of a method of treating cancer according to an exemplary embodiment of present invention;  
         [0028]      FIG. 2  illustrates the in vivo mechanics of the method of the present invention;  
         [0029]      FIG. 3  illustrates an exemplary embodiment of an injection gun suitable for use in injecting a thermopolymer according to the present invention;  
         [0030]      FIG. 4  illustrates a cannula for use in an exemplary embodiment of an intravascular injection system for use in injecting a thermopolymer according to the present invention;  
         [0031]      FIGS. 5-7  illustrate an enlarged view of the distal end of a cannula for use in an exemplary embodiment of an intravascular injection system for use in injecting a thermopolymer according to the present invention; and  
         [0032]      FIG. 8  illustrates an exemplary embodiment of an endoscopic delivery system for use in injecting a thermopolymer according to the present invention. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT  
       [0033]     Illustrative embodiments of the invention are described below. In the interest of clarity, not all features of an actual implementation are described in this specification. It will of course be appreciated that in the development of any such actual embodiment, numerous implementation-specific decision must be made to achieve the developers&#39; specific goals, such as compliance with system-related and business-related constraints, which will vary from one implementation to another. Moreover, it will be appreciated that such a development effort might be complex and time-consuming, but would nevertheless be a routine undertaking for those of ordinary skill in the art having the benefit of this disclosure. The method of inducing ischemia according to the present invention will be discussed in detail below with respect to its exemplary utility in treating cancer. However, it will be appreciated by those skilled in the art (and is within the scope of the present invention) that the methodology of the present invention may also find use in removing organs as method of treatment or for transplant and/or draining and subsequent reduction and isolation of an organ for removal or for an organ to maintain its contents for removal. The method of inducing ischemia disclosed herein boasts a variety of inventive features and components that warrant patent protection, both individually and in combination.  
         [0034]      FIG. 1  is a flowchart illustrating the major steps of a method  10  of treating cancer according to an exemplary embodiment of the present invention. The first step  12  is to locate and diagnose the malignant tumor. This may be accomplished in any number of suitable fashions (currently existing or later developed), including but not limited to the use of Magnetic Resonance Imaging (MRI), X-ray imaging, ultrasound, and/or physical inspection. The second step  14  is to locate each arteriole supplying blood to the tumor. This may be accomplished in any number of suitable fashions (currently existing or later developed), including but not limited to the use of MRI, X-ray imaging, ultrasound, and/or physical inspection. The next step  16  is to inject a flowable thermopolymer into the arterioles leading to cells in and around the tumor. This can be accomplished in any number of suitable fashions (currently existing or later developed), including but not limited to needle injection, intravascular delivery (e.g. catheter based), and/or endoscopic devices. After the thermopolymer cools and solidifies  18 , it will act as a dam to block the arteriole and close off the blood supply to the tumor. In time  20 , the tumor will in effect suffocate and die. At this point  22 , the dead cell mass may be surgically removed if desired.  
         [0035]      FIG. 2  is a schematic illustrating the thermopolymer injection step. In this diagram  30  one can see that the nutrient-rich blood flows from the arteries through arterioles to capillaries that feed cells. Preventing the blood from flowing through the arterioles will divert nutrients from the tumor, and the cells will starve to death. To achieve this, the thermopolymer  32  is injected through an injection needle  34  such that it enters the arterioles leading to cells in and around the tumor. Upon cooling, the thermopolymer  32  will form internal dams within the arterioles that will block the arterioles and divert the blood flow from the tumor.  
         [0036]      FIG. 3  illustrates an exemplary embodiment of an injection gun  50  suitable for use in inserting a thermopolymer  32  according to the present invention. Specifically, injection of thermopolymer  32  through cannula  82  by injection gun  50  is shown. Injection gun  50  has a body  52  with a removable plunger  54  adapted to receive a cylindrical plug of the thermopolymer material  32 . A heater  56  may be provided to heat thermopolymer material  32  and a heater control unit  58  having an adjustable temperature control knob  60  may be provided with a temperature readout at  62 . Electrical leads  64  extend to heater  56 . An injection needle  34  extends from body  52  and has a ceramic sheath  66  about a portion of the proximal end of needle  34 . Cannula  82  may be attached to distal end of needle  34  to facilitate injection into the body. Injection needle  34  may be composed of any number of suitable materials, including but not limited to silver, aluminum, or stainless steel. A hand-operated trigger  68  may be activated for forcing thermopolymer material  32  from the end of needle  34  into cannula  82  upon heating of the thermopolymer material to a predetermined temperature. To assist trigger  68  in exerting an axial force against the plug of thermopolymer  32  in gun  50 , a foot operated hydraulic pump  70  may be provided to supply fluid through lines  72 ,  74  to hydraulic cylinder  76 . A pressure readout is provided at  78 . A suitable piston  80  may exert an axial force against the thermopolymer material  32 . A hydraulic system is effective in providing an axial injection force that may be easily regulated and controlled by personnel performing the procedure.  
         [0037]      FIGS. 4-7  illustrate an exemplary embodiment of an intravascular injection system for use in inserting a thermopolymer according to the present invention.  FIG. 4  shows the main body and distal end  84  of cannula  82 . Located at distal end  84  of cannula  82  is the distal opening of inner lumen  88 .  FIG. 5  represents an enlarged side prospective view of distal end  84  of cannula  82 . Inner lumen  88  contains retractable plunger  94 , shown in the closed position. Inner lumen  88  extends in a generally central manner along the length of cannula  82  and is attached to the distal end of injection needle  34  of injection gun  50  of  FIG. 3  to permit flowage of thermopolymer  32 . Surrounding inner lumen  88  is catheter body  86 . Catheter body  86  may be comprised of any material capable of providing a solid yet flexible and insular housing for inner lumen  88 , including but not limited to rubber, plastic, latex, or silicon. Guide wire  90  extends the length of cannula  82  through guide wire lumen  92 . Guide wire lumen  92  is generally a smaller tube than inner lumen  88 , and is located in a generally superior orientation to inner lumen  88  within catheter body  86 .  
         [0038]      FIG. 6  illustrates the distal end  84  of cannula  82  with retractable plunger  94  in the open position. Retraction of plunger  94  allows for flowage of thermopolymer  32  into the targeted arteriole.  FIG. 7  is a frontal view of the distal end  84  of cannula  82 , illustrating the general orientation of the components. Inner lumen  88  is oriented in a generally central location of cannula  82 . Retractable plunger  94  is located in the interior of inner lumen  88 . Heating element  96  may surround inner lumen  88  in order to facilitate heating (or prevent premature cooling) of thermopolymer  32 . Heating element  96  may comprise any number of suitable elements for heating, including but not limited to ceramics, coils, and the like. Catheter body  86  surrounds inner lumen  88  and, if present, heating element  96 . Guide wire  90  is located inside guide wire lumen  92 , which extends through catheter body  86  and is generally located in a superior position to inner lumen  88  and heating element  96  (if present).  
         [0039]     Guide wire  90  can be inserted into the body by any of a number of well-known methods, such as the Seldinger technique. Once guide wire  90  is placed, cannula  82  is advanced by introducing the proximal end of guide wire  90  into guide wire lumen  92  located at distal end  84  of cannula  82 . Cannula  82  is then passed along guide wire  90  until the desired location is reached within the body. Once cannula  82  is properly inserted, trigger  68  of insertion gun  50  is activated, forcing heated thermopolymer  32  through needle  34 , into cannula  82 , and eventually into the proper arteriole.  
         [0040]      FIG. 8  illustrates an exemplary embodiment of an endoscopic delivery system for use in injecting a thermopolymer according to the present invention. Once a malignant tumor is located in the patient (shown here in the torso, but could be anywhere), the method  10  of treating cancer may be utilized. A trocar  98 , or any other device commonly used by those skilled in the art to insert intravenous cannulae, may be used to facilitate insertion of cannula  82  into the proper arteriole. Once cannula  82  is properly inserted, trigger  68  of insertion gun  50  is activated, forcing heated thermopolymer  32  through needle  34 , into cannula  82 , and eventually into the proper arteriole. Once thermopolymer  32  has been inserted, only a short time is needed to allow for solidification and consequential blockage of the tumor feeding arteriole.  
         [0041]     While the present invention has been shown and described in terms of preferred embodiments thereof, it should be understood that this invention is not limited to any particular embodiment, and that changes and modifications may be made without departing from the true spirit and scope of the invention as defined in the appended claims. By way of example only, the method of inducing ischemia according to the present invention may also find use in removing organs as method of treatment or for transplant. This may be accomplished via oblation or occluding the blood flow, which facilitates the removal of the target organ by restricting blood flow within the organ prior to removal and hence blood loss during removal. In addition, the method of inducing ischemia of the present invention may also find use in maintaining the contents of the target organ during removal, such as by occluding the egress portal (         ) of the target organ via injecting a thermopolymer according to the present invention (as described above with respect to blood flow obstruction).