Patent Publication Number: US-9884028-B2

Title: Methods for treatment of bladder cancer

Description:
RELATED APPLICATIONS 
     This application is a continuation of U.S. non-provisional patent application Ser. No. 13/726,162 filed on Dec. 23, 2014, now U.S. Pat. No. 9,011,411, which is a divisional of U.S. non-provisional patent application Ser. No. 10/941,942 filed Sep. 16, 2004 now U.S. Pat. No. 8,361,490, the entirety of which are hereby incorporated herein by reference. 
    
    
     FIELD AND BACKGROUND OF THE INVENTION 
     The present invention relates to biocompatible drag delivery methods and systems and, more particularly, to systems and methods for treating cancer of an internal cavity such as the urinary bladder. 
     The most common form of bladder cancer is transitional cell carcinoma (TCC), involving the cells that line the urinary tract, accounting for more than 90% of bladder cancers. One treatment for patients with early stage bladder cancer is surgical removal of the tumor, known as Trans-Urethral Resectomy (TUR). However, even after complete excision of a superficial bladder tumor, recurrence rates are up to 75%. Although most recurrences are also superficial, bladder cancer is a multi-focal disease and new tumors may not necessarily occur at the same location. Accordingly, a post-surgery monitoring program is always initiated for early detection of recurrence. The standard monitoring procedure typically includes flexible cystoscopic examinations of the bladder every three to four months for the first two years and, in the absence of recurrence, less frequently thereafter. 
     Flushing of the bladder with different drugs on a regular basis has been shown to significantly reduce the recurrence rate. Specifically, the commonly used agents include Bacillus Calmette-Guerin (BCG), thiotepa, doxorubicin, mitomycin C, Taxol™ and Gemzar™. However, multiple invasive sessions are needed on a regular basis. 
     Furthermore, it has been shown that during TUR, cells released during surgical excision of the tumor tend to migrate, which can lead to new sites of tumor formation. It would be advantageous to provide means for preventing such occurrences while treating the cancer as well. 
     The present invention seeks to remedy the deficiencies of the commonly used method of flushing the internal cavity, providing a more constant treatment while protecting unaffected areas. 
     SUMMARY OF THE INVENTION 
     According to one aspect of the present invention, there is provided a method for treatment of an internal cavity. The method includes incorporating a drug within a biocompatible matrix to form a treatment solution, providing the treatment solution to an interior wall of the cavity, and adjusting the treatment solution so as to provide optimal contact between the treatment solution and the interior wall. 
     According to another aspect of the present invention, there is provided a method for coating an internal cavity. The method includes providing an adapted endoscope, the adapted endoscope including a passageway for the fluid, wherein the passageway has a proximal end located outside of a body, and a distal end configured for insertion into the interior cavity, introducing the distal end into the interior cavity, and introducing the fluid through the passageway and into the internal cavity. 
     According to yet another aspect of the present invention, there is provided a method for treating bladder cancer. The method includes incorporating a cancer-fighting drug into a biocompatible matrix to form a drug carrier solution, introducing the drag carrier solution into the bladder, and coating at least a portion of the bladder with the drug carrier solution. 
     According to further embodiments, the method further includes curing at least a portion of the biocompatible matrix thereby providing a substantially rigid biocompatible drug carrier coating, and leaving the substantially rigid biocompatible drug carrier coating within the bladder for a specified period of time, during which time the cancer-fighting drug is releasable into the bladder. 
     According to yet another aspect of the present invention, there is provided a system for treatment of an internal cavity. The system includes a delivery device with a body having a proximal end and a distal end and a delivery channel formed through the body, an adjuster positioned on the distal end of the body, and a stabilizing mechanism positionable within the adjuster. 
     According to yet an additional aspect of the present invention, there is provided a method for preventing cell migration and adherence within an internal cavity during tumor resection. The method includes coating the internal cavity with a substance, and resecting the tumor through the coating. In one embodiment, the method further includes curing the substance prior to resecting said tumor. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention is herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice. 
       In the drawings: 
         FIGS. 1 a - d    are illustrations of a system positioned in a urinary bladder in accordance with a preferred embodiment of the present invention; 
         FIG. 2  is an illustration of a body of the system of  FIGS. 1 a - d    shown in greater detail; 
         FIG. 3  is a schematic diagram of a configuration of a coating substance in accordance with a preferred embodiment of the present invention; 
         FIGS. 4 a - c    are schematic illustrations of possible configurations of a coating substance in accordance with, several embodiments of the present invention; 
         FIGS. 5 a - d    are illustrations of a system in accordance with another embodiment of the present invention, further including a valve delivery channel; 
         FIGS. 6 a - d    are illustrations of a system in accordance with yet another embodiment of the present invention, showing a rotating aspect; 
         FIG. 7  is an illustration of a system in accordance with an alternative embodiment, wherein a stabilizing mechanism is activatable over a specific area within a bladder; 
         FIGS. 8 a - c    are illustrations of a system in accordance with yet another embodiment of the present invention, wherein tubes are situated on top of a balloon; 
         FIG. 9  is an illustration of a system for flushing an internal cavity, in accordance with an embodiment of the present invention; 
         FIG. 10  is an illustration of a system for delivery of a matrix to an internal cavity, in accordance with an embodiment of the present invention; and 
         FIG. 11  is an illustration of a combination system in accordance with another embodiment of the present invention. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The present invention is of systems and methods for treating an internal cavity by applying a treatment solution to a wall of the internal cavity. Specifically, the present invention can be used to treat the internal cavity by coating the wall with a treatment solution. The term “treatment solution” in the present application encompasses several different embodiments, including a solidifiable matrix with or without a drug or combination of drugs incorporated therein, or a drug solution without a solidifiable matrix, all of which are described in further detail hereinbelow. In a preferred embodiment, a drug or combination of drugs incorporated in a biodegradable polymer is coated onto at least a portion of the internal cavity, acting as a slow-release drug delivery system. The treatment solution can be distributed over an entire area or region for general treatment, or at a specific location for acute treatment. 
     The principles and operation of apparatus and methods according to the present invention may be better understood with reference to the drawings and accompanying descriptions. 
     Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting. 
     Reference is now made to  FIGS. 1 a - d   , which are illustrations of a system  10  positioned in an organ in accordance with a preferred embodiment of the present invention. The organ illustrated herein is a urinary bladder  11 ; however, it should be readily apparent that all descriptions may apply to other organs as well, such as the intestines, stomach, a blood vessel, esophagus, appendix, duodenum, lungs, or any other internal cavity, Urinary bladder  11  has an internal wall  13 , an internal cavity  15  and a neck  17 . Ureters  19 , which deposit urine into urinary bladder  11 , are partially positioned within internal cavity  15 . System  10  includes a delivery device  12  having a body  14  with a proximal end  16  and a distal end  18 , and a delivery channel  20  formed through body  14 . Delivery channel  20  includes an exit port  21  for communication with internal cavity  15 , preferably located at or near a distal end of delivery channel  20 . An adjustment channel  23  is also positioned through body  14 , and includes an adjustment exit port  25  for communication with an adjustor  28 . Proximal end  16  includes a hub  22  having a delivery port  24  and an adjustment port  26 , and is positioned outside of bladder  11 . A configuration of ports and channels in accordance with a preferred embodiment of the present invention is described in greater detail hereinbelow with respect to  FIG. 2 . 
     System  10  is Introduced through neck  17  of bladder  11 , such that distal end  18  is substantially within bladder  11 . Distal end  18  includes an adjustor  28 , designed to adjust a treatment solution  34  introduced through delivery channel  20  within bladder  11 , preferably adjusting the treatment solution so that, it is formed against and conforms to internal wall  13 . In a preferred embodiment, adjuster  28  is an inflatable balloon  30  in fluid communication with inflation port  26  via adjustment channel  23  and adjustment exit port  25 . In an alternative embodiment, adjustor  28  is a brushing mechanism, configured for brushing or spreading treatment solution  34  onto internal wall  13  such as, for example, an airbrush. Control of adjuster  28  is achieved from outside of urinary bladder  11  via adjustment port  26 . In a preferred embodiment, adjustment port  26  is an inflation port  29 , and balloon  30  is inflated or deflated by introduction and removal of a fluid into and out of inflation port  29 . In a preferred embodiment, the fluid is a gas or a combination of gases, such as air. In an alternative embodiment, the fluid is saline. In yet another embodiment, the fluid is water or any other suitable liquid. Inflatable balloon  30  is depicted in  FIGS. 1 a  and 1 b    in a deflated state, and in  FIGS. 1 c  and 1 d    in an inflated state. In an alternative embodiment, adjustment port  26  includes a control mechanism for controlling adjustor  28 , for example, a handle for manually controlling a brushing mechanism. 
     System  10  further includes a stabilizing mechanism  32  for stabilizing treatment solution  34  after it is introduced into urinary bladder  11  via delivery port  24  and adjusted within the bladder via adjustor  28 . In a preferred embodiment, stabilizing mechanism  32  is a curing mechanism  33 , wherein treatment solution  34  includes a curable biocompatible material, and wherein curing mechanism  33  allows at least a portion of treatment solution  34  to cure, forming a substantially rigid material within bladder  11 . In a preferred embodiment, stabilizing mechanism  32  is a light source. In a preferred embodiment, stabilizing mechanism is positioned on body  14 , such that upon insertion of body  14  into urinary bladder  11 , stabilizing mechanism  32  is in place within bladder  11 . In another embodiment, the light source is introduced via delivery channel  20 , and body  14  is transparent. In an alternative embodiment, the light source is introduced through an additional channel, positioned either coaxial with or adjacent to delivery channel  20 . A light source used for curing can be a source of electromagnetic radiation, for example, actinic light. In alternative embodiments, curing mechanism  33  is heat, pressure, or a curing agent or combination of curing agents. Any of the above curing mechanisms may be combined as well. Methods for curing polymers inside body lumens, suitable for the present invention, are disclosed in U.S. Pat. No. 5,849,035 to Pathak et al. and U.S. Pat. No. 5,779,673 to Roth et al., incorporated herein by reference in their entireties. In an alternative embodiment, no curing mechanism is present, and treatment solution  34  comprises self-coring material. 
     Reference is now made to  FIG. 2 , which is an illustration of body  14  of delivery device  12  in greater detail. Hub  22  located at proximal end  16  is positioned outside of the body, and includes two ports: delivery port  24  and adjustment port  26 . Delivery port  24  is in fluid communication, via delivery channel  20 , with exit port  21 . As such, deliver/port  24  is configured for introduction of treatment solution  34  from outside of the body into internal cavity  15  of bladder  11 . Adjustment port  26  is in communication, via adjustment channel  23 , with adjustment exit port  25 . As such, adjustment port is configured for controlling adjuster  28  via injection of a fluid such as air or saline, or via a mechanical method. In a preferred embodiment, adjuster  28  is a balloon  30 , which can be inflated and deflated by introduction and removal of liquid or air through adjustment port  26 . Delivery channel  20  and adjustment channel  23  are both formed within body  14  of delivery device  12 , and may be positioned side by side, coaxially, or in any suitable manner so as to separately deliver the appropriate materials to each of exit ports  21  and  25 . 
     A method of treating an internal cavity, in accordance with a preferred embodiment of the present invention, includes the following steps. Treatment solution  34  is introduced into bladder  11  and more specifically onto bladder wall  13  via delivery channel  20  and exit port  21 , as shown in  FIG. 1 b   . Introduction of treatment solution  34  into delivery channel is done by an infusion bag connected to delivery port  24  or by injection into delivery port  24 . In a preferred embodiment, treatment solution  34  comprises a drag incorporated in a biocompatible matrix. In an exemplary preferred embodiment, the biocompatible matrix is a biodegradable polymer, which can be cured into a substantially rigid biodegradable substance coated on internal wall  13  of bladder  11 . In alternative embodiments, treatment solution is a polymer without drugs or a drug solution without a polymer, as will be described in further detail hereinbelow. Treatment solution  24  is introduced by coating, spraying, smoothing or any other suitable method. After introduction of treatment solution  34  onto bladder wall  13 , adjuster  28  is controlled via adjustment port  26 . In a preferred embodiment, as shown in  FIG. 1 c   , adjuster  28  is a balloon  30  and adjustment port  26  is an inflation port  29 . Balloon  30  is inflated by introduction of a fluid through inflation port  29 . In a preferred embodiment, the fluid is saline. In alternative embodiments, the fluid is air or water. Inflation of balloon  30  causes treatment solution  34  to be trapped between balloon  30  and internal wall  13 . In this way, balloon  30  adjusts treatment solution  34  within bladder  11  by, for example, coating it onto internal wall  13 , adjusting a thickness of the coating, and positioning it in appropriate locations. Balloon  30  may be inflated and deflated several times during the procedure in order to improve the spreading and homogeneity of the polymer on internal wall  13 . Finally, treatment solution is stabilized via stabilizing mechanism  32  as shown in  FIG. 1 d   . Stabilizing can include, for example, curing a curable polymer, solidifying a liquid through thermal, chemical, photochemical, or any other means, or in any way changing a physical form of treatment solution  34  such that its position and properties within bladder  11  are optimized. In an exemplary preferred embodiment, stabilizing mechanism  32  is a curing mechanism such as, for example, a light source. In alternative embodiments, curing is accomplished by adding a curing agent, or by applying a pressure to treatment solution  34 . Treatment solution  34  may also be a self-curing material which is configured to self-cure shortly after it is introduced into bladder  11 . In yet another embodiment, treatment solution  34  is comprised of at least two materials, the combination of which leads to curing thereof. Each of the at least two materials are either mixed together just before introduction into bladder  11  through delivery channel  20 , or are each introduced separately, and mixed within bladder  11 . Finally, balloon  30  is deflated and separated from treatment solution  34 , and delivery device  12  is removed from bladder  11 . If the coating is biodegradable, it will eventually degrade on its own, eliminating the need for further intervention. If the coating is biostable, it will generally require a separate intervention to remove the substance from the cavity, although it may be expelled naturally as well. In an alternative embodiment, balloon  30  is left inside bladder  11  for as long as necessary. 
     In another embodiment, a relatively heavy liquid is first introduced into bladder  11 . A heavy liquid is defined as a liquid with a high molecular weight or a high gravitational weight. Treatment solution  34  is then introduced into bladder  11 , wherein treatment solution  34  is lighter than the heavy liquid. When the patient stands up, the heavy liquid drops to the bottom of the bladder while treatment solution  34  remains at a top portion of bladder  11 . The heavy liquid is, in a preferred embodiment, an oil-based liquid and treatment solution includes a water-based liquid, such that the two are configured to stay separate from one another. In this way, treatment solution  34  does not reach a bottom portion of bladder  11 , including, for example, ureters  19 . 
     In one embodiment, delivery device  12  is an adapted standard endoscope, which includes a delivery channel  20  as one of its lumens. A standard endoscope for use in the present application includes ones available, for example, from Bard Endoscopic Technologies, C.R, Bard Inc. (Billerica, Mass., USA) or Circon Corporation (Richmond, British Columbia, Canada), or any other source for a standard endoscope. By using an endoscope as a delivery vehicle, it is possible to delivery treatment solution  34  while performing a procedure, and while viewing the process through a viewing lens in the endoscope, This would be particularly useful when only specific areas of the bladder are targeted, such as after a tumor resection. Several lumens may be present within delivery device  12  including, for example, an irrigation channel, a viewing channel, a light source, a working channel and a delivery channel. In one embodiment, an endoscope is modified to provide a light guiding channel for delivering light of a variety of wavelengths, such as, for example, ultraviolet light. 
     In an alternative embodiment, treatment solution  34  Is applied to a balloon prior to introduction into bladder  11 . Balloon  30  is then Inserted Into bladder  11  and inflated. Inflation of the balloon with treatment solution  34  thereon results in application of treatment solution  34  to internal wall  13 . 
     In a preferred embodiment, several layers of materials are coated onto internal wall  13 , in addition to treatment solution  34 . For the purposes of description, the combination of layers is referred to herein as coating substance  40 . Reference is now made to  FIG. 3 , which is a diagram of a configuration of coating substance  40  in accordance with a preferred embodiment of fee present invention. A first layer, termed adhesion layer  42 , is closest to internal wall  13  and includes an agent to increase the adherence of treatment solution  34  to internal wall  13 . Adhesion layer  42  has elasticity and an ability to expand and contract, thus conforming to the anatomical morphology of internal wall  13 . An example of such an agent is an eosin based primer. A second layer is a buffering layer  44 . Buffering layer  44  provides control over the amount and/or concentration of treatment solution  34  which reaches internal wall  13 . This is done by manipulating the porosity, thickness and other relevant properties of buffering layer  44 . An example of a material used for buffering layer  44  is cyanoacrylate. A third layer is comprised of treatment solution  34 , coated onto adhesion and buffering layers  42  and  44 . Details regarding possible compositions and configurations of treatment solution  34  are described in greater detail further hereinbelow. A fourth layer is a blocking layer  46 , Blocking layer  46  is designed to control an amount and/or concentration of treatment solution  34  to reach an inner volume of the bladder. In one preferred embodiment, blocking layer  46  is configured to completely prevent treatment solution  34  from reaching internal cavity  15 . In alternative embodiments, blocking layer  46  is configured to allow some amount of treatment solution  34  to reach internal cavity  15 . In one preferred embodiment, blocking layer  46  is a high molecular weight PEG-lactide diacrylate hydrogel. A fifth layer is a separation layer  48 , which can reduce adhesion of the matrix to delivery device  12  and/or adjuster  28 . This layer is virtually non-adhesive, a property which may be achieved by polymer casting or curing. Separation layer  48  prevents adhesion when, for example, balloon  30  is removed from bladder  11  and when bladder  11  is collapsed. An example of a material used for separation layer  48  is cyanoacrylate. Any or all of the layers described above with reference to  FIG. 3  may be used alone or in combination in accordance with the present invention. Furthermore, some or all of the layers may be combined into a polymer matrix and applied to internal wall as a unit. Alternatively, each layer is introduced separately into bladder  11  via delivery channel  20 , or via additional channels which can be included within system  10 . In a preferred embodiment, at least one of the layers is biodegradable. 
     Many different configurations of coating substance  40  are possible. Reference is now made to  FIGS. 4 a - c   , which are schematic illustrations of possible configurations of coating substance  40  in accordance with several embodiments of the present invention. In one embodiment as shown in  FIG. 4 a   , coating substance  40  is a polymer patch, having a middle portion  41  and an edge portion  43 . Middle portion  41  includes treatment solution  34 , while edge portion  43  includes adhesion layer  42  or any type of adhesive substance which enables coating substance  40  to attach to internal wall  13 . Other layers may be included as well. According to another embodiment, as shown in  FIG. 4 b   , an entire surface  45  includes an adhesive portion and treatment solution combined. According to yet another embodiment as shown in  FIG. 4 c   , a multi-layer coating substance includes several layers, each with varying drug concentrations. 
     Reference is now made to  FIGS. 5 a - d   , which are illustrations of system  10  in accordance with another embodiment of the present invention wherein system  10  includes a valve delivery channel  36  instead of or in addition to delivery channel  20 . Valve delivery channel  36  allows treatment solution  34  to be introduced into internal cavity  15  in various locations, and not solely through one delivery channel  20  as in the previously described embodiment, thus providing improved spreading of treatment solution  34 . In one embodiment, delivery channel  20  separates into several channels, each of which is formed through balloon  30  to form valve delivery channel  36 . Each section of valve delivery channel  36  provides a different section of bladder  11  with treatment solution  34 . In another embodiment, several channels are directly connected to one or more ports at proximal end  16 . 
     A method of delivering treatment solution  34  to internal cavity  15  using valve delivery channel is described with reference to  FIGS. 5 a - d   . As shown in  FIG. 5 a   , system  10  is introduced into bladder  11 , with balloon  30  in an unexpanded state. Next, as shown in  FIG. 5 b   , balloon  30  with valve delivery channel  36  therethrough is expanded via inflation port  26 . Once balloon  30  is expanded, treatment solution  34  is introduced through valve delivery channel  36  and onto bladder wall  13 , shown in  FIGS. 5 c  and 5 d   . Balloon  30  may be inflated and deflated as many times as necessary for smoothing and improved spreading of treatment solution  34 . Treatment solution  34  will naturally fill in the gaps and be positioned in between balloon  30  and internal wall  13 . Treatment solution is stabilized via stabilizing mechanism  32  as shown and described in detail with reference to  FIG. 1 d    above. Finally, balloon  30  is deflated and separated from treatment solution  34 , and delivery device  12  is removed from bladder  11 . In an alternative embodiment, balloon  30  is left inside bladder  11  for as long as necessary. 
     Reference is now made to  FIGS. 6 a - d   , which are illustrations of system  10  in accordance with yet another embodiment of the present invention. As shown in  FIG. 6 b   , a single valve delivery channel  36  is positionable within system  10 , and is rotatable around an axis. In a preferred embodiment, a section of balloon  30  is removed, the thickness of which defines a thickness of a delivered amount of treatment solution  34 , The embodiment disclosed in  FIGS. 6 a - d    allows for bursts of delivery of treatment solution  34  into specific areas of bladder  11 . Furthermore, delivery channel  36  is rotatable about an axis, providing a controllable amount of treatment solution application at any point around an inner circumference of internal wall  13 . 
     A method of delivering treatment solution  34  to internal cavity  15  using single valve delivery channel  36  is described with reference to  FIGS. 6 a - d   . System  10  is placed through neck  17  of bladder  11  and positioned within internal cavity  15 . Balloon  30  is then expanded, as shown in  FIG. 6 b   . Treatment solution  34  is introduced into bladder  11  via delivery channel  36 , positioned through balloon  30  such that treatment solution  34  exits through delivery channel and into an inner space between balloon  30  and internal wall  13 , as shown in  FIG. 6 c   . In one embodiment, balloon  30  has a smaller diameter in the area of delivery channel  36  to allow for an increased amount of treatment solution  34  to collect in that space. In another embodiment, balloon  30  has a variable geometry so as to predefine an area of application. System  10  can men be rotated up to 360 degrees, with introduction of additional treatment solution  34  occurring at predetermined times. In one embodiment, treatment, solution  34  is introduced during the entire time of the rotation of system  10 , providing extensive coverage within the parameters of the balloon dimensions and geometry. In another embodiment, treatment solution is introduced only at specific times, resulting in coverage at specific locations. It should be noted that rotation capabilities may be included in any of the other described embodiments as well. Stabilizing mechanism  32 , depicted herein as a curing light, is activated as shown in  FIG. 6 d   . Finally, balloon  30  is deflated and separated from treatment solution  34 , and delivery device  12  is removed from bladder  11 . 
     Reference is now made to  FIG. 7 , which is an illustration of system  10  in accordance with an alternative embodiment. Stabilizing mechanism  32  Is activatable over only a specific area within bladder  11 . Thus, although treatment solution  34  may be applied throughout, an entire internal area of bladder  11 , only one portion of treatment solution  34  is stabilized. Providing partial stabilization and/or curing may be accomplished by, for example, illuminating only a certain portion of bladder  11  with optical collimator lenses. Alternatively, adjustments to balloon  30  may provide partial stabilization by, for example, partially coating balloon  30  with an opaque substance while the remainder of balloon  30  is transparent to a curing light. System  10  can also be rotated up to 360 degrees, with stabilization occurring at predetermined times. In one embodiment, stabilization is done during the entire time of the rotation of system  10 , providing extensive curing. In another embodiment, stabilization is done only at specific times. In a preferred embodiment, treatment solution  34  is a mixture of a drug or drugs incorporated within a biocompatible polymer matrix, wherein the matrix is curable by, for example, a light source. By controlling the emittance area of the light source, the amount of cured matrix can be controlled. This can be done at predetermined locations within bladder  11 . 
     A method of stabilizing treatment solution  34  or coating substance  40  is described with reference to  FIG. 7 . Treatment solution  34  is introduced via delivery channel  20  and exit port  21  to internal cavity  15 . Alternatively, treatment solution  34  or coating substance  40  is introduced via other delivery channels described in accordance with other embodiments of the present invention, such as valve delivery channel  36 , for example. Once treatment solution  34  is within bladder  11 , balloon  30  is inflated so as to smooth or spread treatment solution onto internal wall  13 . A specified area is then stabilized. In a preferred embodiment stabilization is curing and is accomplished by exposure of one specific area of treatment solution  34  to a curing mechanism, such as a light source, a heat source or a curing agent. System  10  can also be rotated so as to provide, curing and/or stabilization at several specific areas of treatment solution  34 . Finally, balloon  30  is deflated and separated from treatment solution  34 , and delivery device  12  is removed from bladder  11 . 
     Reference is now made to  FIGS. 8 a - c   , which are illustrations of system  10  in accordance with yet another embodiment of the present invention. Delivery device  12  includes at least one external channel  50 , positioned on an exterior portion of balloon  30  and movable with respect to balloon  30 . In a preferred embodiment, pressure can be applied to channel  50 , thereby causing material contained within channel  50  to be pushed out. The pressure is controllable from outside the body, either by manual means or via a strain release mechanism (not shown). The strain release mechanism may be, for example, a cap or a ring positioned on a proximal end of channel  50 . When balloon  30  is in an inflated state, external channel  50  is squeezed between balloon  30  and internal wall  13 . A distal end of external channel  50  is initially located at a top portion of balloon  30 . As treatment solution  34  is introduced, external channel  50  is pulled proximally, and strain release mechanism causes treatment solution to be squeezed out of channel  50  and onto balloon  30 . In another embodiment, external channel  50  is positioned within a groove  52  formed in a body of balloon  30 . Thus, an exact path of treatment solution delivery can be mapped out, providing many different options for coverage. For example, if groove  52  is formed in a zigzag configuration, treatment solution  34  will be delivered and spread in approximately the zigzag configuration, providing more coverage than a straight, line. Any other shape for groove  50  can be envisioned and is included within the scope of the present invention. Furthermore, external channel  50  can include any number of external channels. 
     A method of delivering treatment solution  34  to internal cavity  15  using external channels  50  is described with reference to  FIGS. 8 a - c   . First, treatment solution  34  is introduced into external channels  50 . One or several external ports provide access to external channels  50  from outside the body. Once treatment solution  34  is fully located within external channels  50 , balloon  30  is inflated. External channels  50  are then pulled in a proximal direction, either one by one or simultaneously. By providing pressure either manually or via strain release mechanism, treatment solution  34  is released as external channels  50  are pulled back. During the procedure, balloon  30  may be inflated and deflated as many times as necessary, until treatment solution is sufficiently distributed onto internal wall  13 . Stabilization is then done, as described above, followed by deflation of balloon  30  and removal of delivery device  12  from bladder  11 . Three stages of pulling are shown in  FIGS. 8 a   - c.    
     Reference is now made to  FIG. 9 , which is an illustration of a system  10  for delivery of treatment solution  34  in accordance with another embodiment of the present invention. Treatment solution  34  is a drug solution, and does not include a polymer or curable matrix. In this embodiment, treatment solution  34  is designed as a wash for bladder  11 . In a preferred embodiment no adjustor  28  is included, since treatment solution  34  is designed to flow freely within internal cavity  15 . Delivery device  12  further includes a stopper  60 , designed to prevent treatment solution  34  from blocking ureters  19 . Stopper  60  is positioned on body  14  of delivery device  12 . In a preferred embodiment, stopper  60  includes inflatable balloons, which are deflated daring introduction of delivery device  12  into bladder  11  and inflated prior to introduction of treatment solution  34 . In alternative embodiments, stopper  60  is a double-J stopper or of a pig-tail configuration, a ureter catheter, or any other mechanism for blocking. 
     A method of treating a bladder  11  in accordance with an embodiment of the present invention is described with reference to  FIG. 9 . First, delivery device  12  is inserted into bladder  11 . Next, stopper  60  is activated. In one embodiment, activation of stopper  60  is via inflation of balloons. In another embodiment, activation of stopper  60  is via a mechanical mechanism, such as removal of a sheath for release of stopper  60 . Treatment solution  34  is then introduced into bladder  11  and allowed to flush internal cavity  15 . Finally, stopper  60  is deactivated, either by deflation of balloons or by mechanical means, and delivery device  12  is removed from the bladder. Treatment solution  34  then flows out of the bladder automatically. 
     Reference is now made to  FIG. 10 , which is an illustration of a system  10  for delivery of treatment solution to a bladder  11  in accordance with another embodiment of the present invention. Treatment solution  34  is a polymer solution, with or without a drug or drug combination incorporated within. Treatment solution is introduced via delivery channel  20  and allowed to spread freely within internal cavity  15 . Delivery device  12  further includes a stopper  60 , designed to prevent treatment solution  34  from blocking ureters  19 . Stopper  60  is positioned on body  14  of delivery device  12 . In a preferred embodiment, stopper  60  includes inflatable balloons, which are deflated during introduction of delivery device  12  into bladder  11  and inflated prior to introduction of treatment solution  34 . In alternative embodiments, stopper  60  is a double J stopper or of a pig-tail configuration is a double-J stopper or of a pig-tail configuration, a ureter catheter, or any other mechanism for blocking. 
     A method of treating an internal cavity  15  in accordance with an embodiment of the present Invention is described with reference to  FIG. 10 . First, delivery device  12  is inserted into internal cavity  15 . Next, stopper  60  is activated. In one embodiment, activation of stopper  60  is via inflation of balloons. In another embodiment, activation of stopper  60  is via a mechanical mechanism, such as removal of a sheath for release of stopper  60 . Treatment solution  34  is then introduced into bladder  11  and allowed to spread freely. Next, stabilizing mechanism  32  stabilizes treatment solution  34 . In a preferred embodiment, stabilization is curing and is done by a curing mechanism such as a light source, a heat source, or a curing agent. Alternatively, treatment solution  34  is self-curing. Stopper  60  is then deactivated, either by deflation of balloons or by mechanical means, and delivery device  12  is removed from the bladder. In one embodiment, treatment solution  34  does not include a drug or drug combination, and is used for coating internal surface  13 . In another embodiment, treatment solution  34  does include a drug or drug combination as described in further detail hereinbelow. 
     Reference is now made to  FIG. 11 , which is an illustration of a system  10  in accordance with yet another embodiment of the present invention. System  10  includes a delivery device  12  having a proximal end  16 , a distal end  18  and a body  14  connecting proximal and distal ends  16  and  18 . Adjuster  28  is positioned at distal end  18 . In a preferred embodiment, adjustor  28  is a balloon  30 , in fluid communication with adjustment port  26 , as described above with reference to  FIG. 2 . Further, stopper  60  is positioned on body  14 , proximal to adjustor  28 . In a preferred embodiment, stopper  60  is a stopper balloon  62 , having an inflation channel which is separate from adjustment channel  23  and is controlled separately via a stopper port  64 . In alternative embodiments, stopper  60  is a double-J stopper or of a pig-tail configuration, a ureter catheter, or any other mechanism for blocking. 
     A method of treating an internal cavity  15  in accordance with an embodiment of the present invention is described with reference to  FIG. 11 . First, delivery device  12  is inserted into internal cavity  15 . Next, stopper  60  is activated. In one embodiment, activation of stopper  60  is via inflation of balloons. In another embodiment, activation of stopper  60  is via a mechanical mechanism, such as removal of a sheath for release of stopper  60 . Treatment solution  34  is then introduced into bladder  11  and allowed to spread freely. Adjustor  28  is then activated so as to adjust treatment solution  34  within internal cavity  15 . In a preferred embodiment, adjustor  28  is a balloon, which can be inflated and deflated as needed so as to provide optimum spreading of treatment solution  34 . Next, stabilizing mechanism  32  stabilizes treatment solution  34 . In a preferred embodiment, stabilization is curing and is done by a curing mechanism such as a light source, a heat source, or a curing agent. Alternatively, treatment solution  34  is self-curing. Balloon  30  is then deflated. Stopper  60  is then deactivated, either by deflation of balloons or by mechanical means, and delivery device  12  is removed from the bladder. It should be readily apparent that any of the embodiments described herein may be combined with a stopper such as the one described in reference to  FIG. 12 . 
     Alternative methods for preventing blockage of ureters  19  are also possible. For example, ureter catheters can be inserted prior to insertion of delivery device  12 . Alternatively, stoppers can be inserted prior to insertion of delivery device  12 . In an alternative method, a patient can be relieved of urine prior to stabilization of treatment solution  34 . In an alternative embodiment, a heavy liquid solution introduced into bladder  11  prevents treatment solution  34  from reaching and blocking ureters  19 . Alternatively, when selective application of treatment solution and/or stabilization thereof is performed, such as described above with reference to  FIGS. 6 a - c   ,  7  and  8   a - b , it is possible to deliberately avoid application and/or stabilization of treatment solution  34  at the locations of the ureter orifices, thereby protecting the orifices. If internal cavity  15  is a cavity other than bladder  11 , any other branching member can be similarly protected. 
     In one embodiment of the present invention, treatment solution  34  is used to coat an internal cavity prior to surgical removal of a cancerous tumor, so as to prevent cell migration from causing a new cancerous growth elsewhere in the cavity. Treatment solution  34  includes a curable matrix with or without drugs. Treatment solution  34  is applied to an entire internal wall  13  and optionally cured as described with respect to the embodiments above. When a transparent matrix is used, such as a hydrogel, for example, removal of the tumor can be done through the coating. Thus, the covered areas are protected from cell migration. The resected area can then be recoated, if desired, according to any of the methods described above. 
     In an alternative embodiment of the present invention, treatment solution  34  is used to treat an ulcer of the stomach. Treatment solution  34  is applied to the specific location of the ulcer within the stomach, in accordance with one of the embodiments described above, wherein selective application of treatment solution  34  is possible. In a preferred embodiment, for treatment of stomach ulcers, treatment solution  34  is comprised of a halobacter bacteria with an antibiotic in a polymer gel. 
     Treatment Solution: 
     Treatment solution  34  comprises a solidifiable matrix with or without a drug or combination of drugs incorporated therein, or a drug solution without a solidifiable matrix. In a preferred embodiment, treatment solution  34  comprises a drug or drug combination incorporated into a biocompatible matrix. The drug may be dissolved or dispersed therein. In one embodiment, the drug or drag combination is incorporated within the matrix prior to delivery through system  10 . In an alternative embodiment, the drug or drug combination is mixed with the matrix once it is within bladder  11  by separate introduction into internal cavity  15 . In a preferred embodiment, the biocompatible matrix is a polymer matrix, which can be chemically or physically altered while in vivo. Such alterations include, but are not limited to solidification, curing, cross-Sinking and the like. Examples of such polymers are well known in the art, and may include, for example, carboxylic acids such as glycolic acid and lactic acid, polyurethanes, polyesters such as poly(ethlene terephthalate), polyamides such as nylon, polyacrylonitriles, polyphosphazines, polylactones such as polycaprolactone, and polyanhydrides such as poly[bis(p-carboxyphenoxy)propane anhydride] and other polymers or copolymers such as polyethylene, polyvinyl, chloride and ethylene vinyl acetate. The polymers can include hydrophobic and hydrophilic polymers. 
     Other bioabsorbable polymers could also be used either singly or in combination, such as homopolymers and copolymers of delta-valerolactone, and p-dioxanone as well as their copolymers with caprolactone. Further, such polymers can be cross-linked with bis-caprolactone. Any of the commonly known drug carrier polymeric materials may be used as well, such as polyanhydrides. Examples of biodegradable polymer matrix materials which are suitable for use in the present application are disclosed in U.S. Pat. No. 5,914,345 to Slepian et al., U.S. Pat. No. 6,443,941. to Slepian et at, U.S. Pat. No. 6,689,200 to Scarborough et al. and U.S. Pat. No. 6,352,710 to Sawhney et al., incorporated by reference herein in then entireties. 
     In an alternative embodiment, biostable polymers can be used. Examples of biostable polymers are PVP, polyurethane, or any other biocompatible polymer. Since biostable polymers will not degrade in the body, they will need to be retrieved separately after the treatment process is complete. Alternatively, such a material may be naturally released from the body a little at a time. 
     In a preferred embodiment, the drug is an anti-cancer agent, which can include but is not limited to Bacillus Calmette-Guerin, thiotepa, doxorubicin, Gemzar™, Mitomicin C, epirubicin, thiotepa, or Taxol™. Other therapeutic agents may be included as well, including, for example, an antibiotic for treatment of intra-cavity ulcer, gastritis, colitis etc. Gemzar™ is a commercially available form of gemcitabine (2′, 2′-difluoro-deoxycytidine, dFdC), which is a pyrimidine analogue of deoxycytidine in which the deoxyribose moiety contains two fluorine atoms at the 2′-position. (See Heinemann et al. Cancer Res 1988 48:4024). Taxol™ is a commercially available form of paclitaxel. 
     In a preferred embodiment, treatment solution  34  comprises Gemzar™ with polyethylene glycol, biodegradable polylactic acid, thimethylene carbonated and polymerizable acrylic ester. In an alternative embodiment, treatment solution  34  includes an antibiotic in a polymer matrix. In an alternative embodiment, treatment solution  34  includes a halobacter bacterium in a polymer gel matrix. It should be apparent that any combination of drugs and carriers can be used and are included in the scope of the invention. 
     It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination. 
     Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.