Patent Publication Number: US-2011071468-A1

Title: Systems and methods for applying a selected treatment agent into contact with tissue to treat sphincter dysfunction

Description:
RELATED APPLICATIONS 
     This application is a continuation of co-pending patent application Ser. No. 12/313,845 filed 25 Nov. 2008, which is a divisional of U.S. patent application Ser. No. 10/912,329, filed 5 Aug. 2004, which is a divisional of U.S. patent application Ser. No. 09/994,379, filed Nov. 26, 2001, which is a continuation-in-part of U.S. patent application Ser. No. 09/304,737, now U.S. Pat. No. 6,464,697, filed May 4, 1999, and a continuation-in-part of U.S. patent application Ser. No. 09/556,169, now U.S. Pat. No. 6,645,201, filed Apr. 21, 2000, which claims the benefit of U.S. Provisional Patent Application Ser. No. 60/143,749, filed Jul. 14, 1999, and a continuation-in-part of U.S. patent application Ser. No. 09/090,794, filed Jun. 4, 1998 and entitled “Method for Treating a Sphincter” (now abandoned). 
    
    
     FIELD OF THE INVENTION 
     In a general sense, the invention is directed to systems and methods for treating interior tissue regions of the body. More specifically, the invention is directed to systems and methods for treating dysfunction in body sphincters and adjoining tissue, e.g., in and around the lower esophageal sphincter and cardia of the stomach, or in and around the anal sphincter complex. 
     BACKGROUND OF THE INVENTION 
     Dysfunction of a sphincter in the body can lead to internal damage or disease, discomfort, or otherwise adversely affect patient quality of life. 
     Gastroesophageal reflux disease (GIRD), for example, is a common disorder caused most commonly by frequent transient relaxations of the lower esophageal sphincter (LES). If the lower esophageal sphincter fails to function properly, stomach contents, including acid, enzymes, and bile may flow backwards into the esophagus, causing heartburn or other disease symptoms, damage to the esophagus, and the development of precancerous lesions. 
     Fecal incontinence is the involuntary passage of solid or liquid stool through the anal canal. This is caused most commonly by previous damage to or aging of the external and/or internal sphincter muscles in the anal canal. Secondary causes are improper sensing and control of solid or liquid stool within the rectum. 
     The disease states of GERD and fecal incontinence have in common a defective sphincter barrier as a mechanism of the disease. The end result is the development of GERD and fecal incontinence symptoms due to inadequate barrier function. In both GERD and fecal incontinence, inadequate barrier function can be the result of either a mechanical defect in the sphincter, a low resting pressure in the sphincter, an overly compliant sphincter, abnormal afferent nerve impulses that trigger transient sphincter relaxations, or improper sensing of and control of lumenal contents. 
     SUMMARY OF THE INVENTION 
     The invention provides systems and methods that apply a selected treatment agent into contact with tissue at, or in, the region of a dysfunctional sphincter in order to affect improved sphincter barrier function and improve a disease state. The systems and methods may be used as either a primary treatment modality, or applied as a supplementary treatment before, during or after a primary intervention. 
     According to one aspect of the invention, the treatment agent includes at least one sub-type of a cytokine. Delivery of a cytokine to tissue evokes a desired tissue response, which can include, e.g., an initiation of a localized healing process including influx of white blood cells and fibroblasts, followed by deposition of collagen, and a subsequent reduction in tissue compliance and tightening. These effects will result in improved sphincter barrier function. The cytokine treatment agent may be applied to the surface of a tissue, or, alternatively, it may be injected below the surface of the tissue, including the submucosa, the sphincter itself, or the area surrounding the sphincter. 
     According to another aspect of the invention, the treatment agent may include a tissue bulking agent, which is injected into subsurface tissue, including the submucosa, the sphincter, or the area surrounding the sphincter. Presence of the bulking agent results in additional tissue compliance reduction and tightening to improve sphincter barrier function. 
     According to another aspect of the invention, the treatment agent includes at least one vanilloid compound. Presence of the vanilloid compound evokes a desired tissue response, which includes at least one of the following, e.g., the interruption of afferent nerve impulses which lead to impaired sphincter function or diminished pain impulses from the treated area. The vanilloid treatment agent may be applied to surface tissue, or, alternatively, it may be injected into subsurface tissue, including the submucosa, the sphincter, or the area surrounding the sphincter. In one embodiment, the systems and methods apply energy to the tissue region to form at least one lesion in conjunction with application of the treatment agent. 
     Features and advantages of the inventions are set forth in the following Description and Drawings, as well as in the appended Claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS. 1A and 1B  are schematic views of a system for treating tissue that includes a treatment device with a tissue piercing member that embodies features of the invention,  FIG. 1A  showing the treatment device deployed in a sphincter tissue region and  FIG. 1B  showing the treatment device piercing the tissue region to inject a treatment agent into the sphincter; 
         FIGS. 2A and 2B  are schematic views of a system for treating tissue that includes a treatment device with multiple tissue piercing members that embodies features of the invention,  FIG. 2A  showing the treatment device deployed in a sphincter tissue region and  FIG. 2B  showing the treatment device piercing the tissue region to inject a treatment agent into the sphincter; 
         FIG. 3  is an embodiment of a tissue treatment device that takes the form of a syringe and a needle for injecting a treatment agent into a sphincter tissue region that can be visualized from outside the body, e.g., the anal sphincter complex; 
         FIG. 4  is an embodiment of a tissue treatment device for injecting a treatment agent into a sphincter tissue region that cannot be visualized from outside the body, e.g., in and around the LES; 
         FIG. 5  is a schematic view of a system that includes an embodiment of a treatment device for injecting a treatment agent as well as forming lesions in and around the LES to treat GERD; 
         FIG. 6  is a perspective view, with portions broken away and in section, of the treatment device shown in  FIG. 5 , with the basket element carried by the device shown in a collapsed condition for deployment to a targeted tissue region; 
         FIG. 7  is a perspective view, with portions broken away, of the treatment device shown in  FIG. 5 , with the basket element carried by the device shown in an expanded condition, as it would be when ready for use in a targeted tissue region; 
         FIG. 8  is a perspective view, with portions broken away, of the treatment device shown in  FIG. 5 , with the basket element carried by the device shown in an expanded condition, and with electrodes carried by the basket element extended for use in a targeted tissue region; 
         FIG. 9  is an enlarged end view of one of the multiple lumen spines that form the basket element shown in  FIGS. 6 to 8 , showing the multiple interior lumens that the spine possesses; 
         FIG. 10  is a top view of the multiple lumen spine shown in  FIG. 9 , showing the different functional elements that the interior lumens of the spine carry; 
         FIG. 11  is an enlarged view of a portion of one of the multiple lumen spines that form the basket element shown in  FIGS. 6 to 10 , showing an electrode deployed through an opening in one of the spines; 
         FIG. 12  is a perspective view of an embodiment of a treatment device for injecting a treatment agent as well as forming lesions in and around tissue in the lower gastro-intestinal tract, the treatment device having an array of electrodes shown in a retracted position; and 
         FIG. 13  is a perspective view of the device shown in  FIG. 5 , with the array of electrodes shown in their extended position. 
     
    
    
     The invention may be embodied in several forms without departing from its spirit or essential characteristics. The scope of the invention is defined in the appended claims, rather than in the specific description preceding them. All embodiments that fall within the meaning and range of equivalency of the claims are therefore intended to be embraced by the claims. 
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     This specification discloses various catheter-based systems and methods for treating dysfunction of sphincters and adjoining tissue regions in the body. The systems and methods are particularly well suited for treating these dysfunctions in the lower gastrointestinal tract, e.g., in the intestines, rectum and anal canal. The systems and methods are also particularly well suited for treating these dysfunctions in the upper gastrointestinal tract, e.g., in the lower esophageal sphincter and adjacent cardia. For this reason, the systems and methods will be described in these contexts. 
     Still, it should be appreciated that the disclosed systems and methods are applicable for use in treating other dysfunctions elsewhere in the body, e.g., for restoring compliance to or otherwise tightening interior tissue or muscle regions. The systems and methods that embody features of the invention are also adaptable for use with systems and surgical techniques that are not necessarily catheter-based. 
     I. System Overview 
     A tissue treatment system  10  that embodies features of the invention is shown in  FIG. 1 . The tissue treatment system  10  includes a tissue treatment device  12  and an apparatus  14  to deliver the tissue treatment device  12  to a tissue region  16  where a sphincter targeted for treatment is located. The treatment system  10  also includes a source  18  of a treatment agent  20 . 
     A. The Tissue Treatment Device 
     The tissue treatment device  12  serves to apply the treatment agent  20  to the targeted sphincter tissue region  16  to obtain a desired therapeutic effect. The therapeutic effect can comprise either a physical alteration of the sphincter or tissue adjacent to the sphincter, or a neurologic alteration of nerve impulse pathways innervating the sphincter or tissue adjacent to the sphincter, or both. 
     The tissue treatment device  12  includes one or more agent delivery ports  22 . The one or more delivery ports  22  can apply the treatment agent  20  to surface tissue in the region  16 . Desirably (as  FIG. 1  shows), the port  20  is located at the end of a tissue piercing member  24 . In this arrangement, the treatment agent  20  may be injected into subsurface tissue, including the submucosa, the sphincter, or the area surrounding the sphincter. 
     The tissue treatment device  12  can include single or multiple ports  22  located single or multiple tissue piercing members  24  to inject the treatment agent  20 . As  FIG. 1  shows, a single tissue piercing member  24  (with a single port  22 ) may be used. Alternatively, as  FIG. 2  shows, the treatment device  24  can carry multiple tissue piercing members  24 , each with a port  22 . Desirably, the multiple tissue piercing members  24  are arranged in a spaced-apart array, to apply the treatment agent  20  in a prescribed pattern at the targeted site. 
     Alternatively, the tissue treatment device  12  may employ air powered, needle-less injection technology. 
     B. The Delivery Device 
     The configuration of the delivery apparatus  14  for the device  12  can also vary, depending upon the accessibility of the treatment site and the particular treatment objectives desired. 
     If the treatment site can be directly visualized—for example, sphincters in the anal canal—the delivery apparatus  14 , the source  18 , and the treatment device  12  can comprise a syringe  100  and a needle  102 , as  FIG. 3  shows. 
     If the treatment site can not be directly visualized or is otherwise not as readily accessible—for example, the LES or cardia—the delivery apparatus  14  can comprise an endoscope  106  having an interior lumen  104  passed down the esophagus through the mouth, as  FIG. 4  shows. In this arrangement, the treatment device  12  is desirably carried on the distal end of a catheter tube  108  for passage through the endoscope lumen  104  to the targeted site. A guidewire may be used, if desired, to further facilitate deployment of the endoscope and treatment device to the targeted site. 
     As  FIGS. 5 to 11  and  12  to  13  further show (and as will be described in greater detail later), the treatment device  12  can be integrated with other sphincter treatment devices, particularly if another treatment modality or therapeutic result is contemplated in combination with the application of the treatment agent  20 , e.g., the formation of lesions. 
     C. The Tissue Treatment Agent 
     The treatment agent  20  is selected from a group of candidate agents based upon the physiologic effect or effects that are desired. One or more candidate agents may be applied simultaneously, or an agent(s) may be applied as a supplementary treatment before, during or after a primary intervention. 
     In the illustrated embodiment, the group consists essentially of three candidate agents: (1) Cytokine Sub-Types; (2) Tissue Bulking Agents; and (3) Vanilloid Compounds 
     1. Cytokine Subtypes 
     The treatment agent  20  can include one or more subtypes of cytokines. A cytokine, in the natural state within the body, is a protein produced and released by a biological cell that has an effect on the local environment surrounding the cell. Cytokines are involved in many cellular processes, such as wound healing. Application of cytokines to a sphincter could be performed with an intent to improve the barrier function. The mechanism of action would depend on the specific cytokine utilized. The term “cytokine subtype” as used herein means any polypeptide that affects the functions of other cells, and is a molecule which modulates interactions between cells in the immune or inflammatory response. A cytokine subtype includes, but is not limited to monokines and lymphokines regardless of which cells produce them. For instance, a monokine is generally referred to as being produced and secreted by a mononuclear cell, such as a macrophage and/or monocyte but many other cells produce monokines, such as natural killer cells, fibroblasts, basophils, neutrophils, endothelial cells, brain astrocytes, bone marrow stromal cells, epideral keratinocytes, and B-lymphocytes. Lymphokines are generally referred to as being produced by lymphocyte cells. Examples of cytokine subtypes include, but are not limited to, interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF alpha) and tumor necrosis factor beta (TNF beta). 
     Other cytokine subtypes include TGF-β, (transforming growth factor); PDGF (platelet derived growth factor); FGF (basic fibroblast growth factor): IGF-1 (insulin-like growth factor 1); EGF (epidermal growth factor); and VEGF. Some of these cytokines are available commercially, could be produced commercially, or can be extracted from a persons harvested platelets (platelet releasates). The effects of a given cytokine upon tissue physiology can include one or more of the following: smooth muscle and fibroblast mitogenic effects (induces division and growth of cells) stimulation of the release of cytokines from other cells; chemoattractant (bringing new healing cells into local region); decrease of collagen enzyme activity allowing collagen to build up; inflammation; and angiogenesis (development of new blood vessels). 
     The treatment agent  20  can include a cytokine sub-type or combination of cytokine sub-types, alone or in combination with other substances. The cytokine-containing treatment agent can be applied by the port or ports  22  to the mucosal lining, or injected into the sphincter muscle, or applied extrinsically to the outside of the sphincter. 
     The cytokine-containing treatment agent  20  can be a solution, a gel, a powder, a pellet, or other form. The treatment agent may be released immediately, or, be a sustained release product such as a slow released implant, slow release gel, coated pellet, microsphere, or other form. 
     The cytokine-containing agent  20  may be applied or injected as primary therapy, or applied as a supplementary treatment before, during or after a primary intervention. For example, as will be described later, radio frequency (RF) energy may be used to induce the wound healing process, followed by cytokine application to facilitate more exuberant wound healing. 
     The application of a single cytokine or mixture thereof, as primary, neoadjuvant, or adjuvant therapy for a sphincter disease could have the various mechanical and therapeutic effects. With or without an inciting wound event (such as RF), cytokines can serve to initiate the process of healing within the local region. This process includes, but is not limited to, influx of white blood cells and macrophages, stimulation of fibroblast and smooth muscle division and collagen secretion, new blood vessel growth, wound contraction and tightening, maturation of the new or existing collagen framework, and reduced tissue compliance. These tissue effects could improve the barrier function of defective sphincter complexes in GERD, fecal incontinence, and other possible disorders. 
     Examples of cytokine materials that can be used include commercially available Regranex, which is recombinant human PDGF-BB. This material has been applied as a gel for promoting the healing of diabetic foot ulcers. Platelet granules contain many of the cytokines listed above, and the cytokines can be extracted with a fairly simple technique (platelet releasates technique). Platelets (harvested as a pooled platelet product or from autologous donation) provide a source of cytokines for extraction. TGF-β and PDGF are considered to be the most important substances for the purpose of initiating the wound healing process. 
     2. Tissue Bulking Agents 
     The treatment agent  20  can include one or more tissue bulking agents. Examples of tissue bulking agents that can be used include collagen, dermis, cadaver allograft material, or ePTFE (expanded poly-tetrafluoroethyene) pellets. 
     The tissue bulking treatment agent  20  can injected by the port or ports  22  into the sphincter muscle, or applied extrinsically to the outside of the sphincter. 
     The tissue bulking treatment agent  20  may be applied or injected as primary therapy, or, or applied as a supplementary treatment before, during or after a primary intervention. For example, as will be described later, radio frequency (RF) energy can be applied to the injected bulking agent  20  to change its physical characteristics, e.g., to expand or harden the bulking material, to achieve a desired effect. 
     3. Vanilloids and Related Substances 
     The treatment agent  20  can comprise a vanilloid compound. Vanilloid compounds have a unique capacity to bind to a membrane receptor in sensory neurons. Capsaicin is one of many vanilloid compounds. Capsaicin is a powerful basic compound which is derived from chili peppers. 
     The specific neuron for capsaicin is deemed “VR1”. This receptor is expressed only on small unmyelinated C-fibers (nerves typically involved in special visceral sensation and pain) 
     Exposure to vanilloid compounds variably reduces the responsiveness of the neuron to stimuli. In many cases, the neuron may actually degenerate temporarily or permanently, thus impairing transmission of pain signals or other special sensory signals. 
     The term “vanilloid compound” as used herein means a compound or a mixture of compounds having a biologically active vanillyl group. Vanilloid compounds include both naturally occurring vanilloids, synthetic vanilloids, pharmaceutically acceptable salts of the vanilloid compound (whether natural or synthetic) as well as pharmaceutically acceptable derivatives and/or analogues thereof (whether natural or synthetic). 
     Examples of natural vanilloid compounds include both the crude extracts and the purified extracts of active vanilloid compounds from: capsicum, cayenne pepper, black pepper, paprika, cinnamon, clove, mace, mustard, ginger, turmeric, papaya seed and the cactus-like plant Euphorbia resinifera. 
     Synthetic vanilloid compounds such as synthetic capsaicin are disclosed in WO 96/40079, which is incorporated herein by reference. The vanilloid compound family includes: Capsaicin; Dihydrotapsaicin: Nordihydrocapsaicin Homocapsaicin Homodihydrocapsaicin. Alternatively, resiniferotoxin (RTX) is derived from the euphorbia cactus and is considered a capsaicin-like compound. This substance also activates the VR1 receptor and attenuates or eliminates afferent nerve function, although it may not illicit the rapid heat sensation that other vanilloids produce. 
     Other examples of vanilloid compounds include capsaicin ((E)-(N)-[(4-hydroxy-3-methoxyphenyl)-methyl]-8-methyl-6-nonenamide); eugenol (2-methoxy-4-(2-pro-penyl)phenol); zingerone (4-(4-hydroxy-3-methoxyphenyl-2-butanone); curcumin (1,7-bis(4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione); piperine (1-[5-(1,3-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine) ; resin-iferatoxin(6,7-deepoxy-6,7-didehydro-5-deoxy-21-dephenyl-21-(phenylmethyl)- 20 -(4-hydroxy-3-thoxybenzene-acetate)) or pharmaceutically effective salts, analogues, derivatives or equivalents thereof. The treatment agent  20  can include capsaicin, another vanilloid compound, RTX, or combination thereof, alone or in combination with other substances (which will be generically called a vanilloid-containing treatment agent  20 ). 
     The vanilloid-containing treatment agent can be applied through the port  22  or ports  22  to the mucosal lining or extrinsically to the outside of the sphincter. 
     The vanilloid-containing treatment agent can also be injected into the target organ wall, such as the gastric cardia and LES for the treatment of GERD or the anal sphincters for treatment of fecal incontinence. 
     The treatment agent  20  can be a solution, a gel, a powder, a pellet, or other form. The treatment agent may be released immediately, or, be a sustained release product such as a slow released implant, slow release gel, coated pellet, microsphere, or other form. 
     The vanilloid-containing treatment agent  20  may be applied or injected as primary therapy, or applied as a supplementary treatment before, during or after a primary intervention. For example, RF energy may be used to incite a wound, followed by application of the vanilloid-containing treatment agent to facilitate exuberant wound healing. 
     In GERD and fecal incontinence, the use of a vanilloid-containing treatment agent can serve to interrupt afferent nerve impulses could therefore be of significant therapeutic benefit. In GERD, the use of a vanilloid-containing treatment agent can serve to interrupt afferent impulses which trigger transient lower esophageal sphincter relaxations, a common mechanism for GERD. 
     In fecal incontinence, the use of a vanilloid-containing treatment agent can serve to potentially limit the fecal sampling reflex, which may lead to fecal leakage events. Additionally, fecal incontinence may be caused in some patients by abnormal nerve feedback pathways in the anal canal and rectum, which could be favorably modulated by application of vanilloid-containing agents. 
     An example of vanilloid materials that can be used is produced by Afferon and is called RTX, which has been instilled into the lumen of the urinary bladder for the treatment of urge incontinence. There are also several topical, over-the-counter capsaicin products for topical analgesic applications. 
     II. Devices for the Treatment of GERD 
     Another tissue treatment device  26  well suited for treating GERD by injecting one or more treatment agents  20  in tissue regions at or near the LES or cardia is shown in  FIG. 5 . The device  26  is also well suited for applying radio frequency energy to these tissue regions, alone or in combination with injection of the treatment agent  20 , to form lesions. 
     The device  26  includes a handle  28  made, e.g., from molded plastic. The handle  28  carries a flexible catheter tube  30 . The catheter tube  30  can be constructed, for example, using standard flexible, medical grade plastic materials, like vinyl, nylon, poly(ethylene), ionomer, poly(urethane) poly(amide), and poly(ethyleneterephthalate). The handle  28  is sized to be conveniently held by a physician, to introduce the catheter tube  30  into the tissue region targeted for treatment. The catheter tube  30  may be deployed with or without the use of a guide wire (not shown). 
     The catheter tube  30  carries on its distal end an operative element  36 . The operative element  36  can take different forms and can be used for either therapeutic purposes, or diagnostic purposes, or both. The operative element  36  can support, for example, a device for imaging body tissue, such as an endoscope, or an ultrasound transducer. The operative element  36  can also support a device to deliver a drug or therapeutic material to body tissue. The operative element  36  can also support a device for sensing a physiological characteristic in tissue, such as electrical activity, or for transmitting energy to stimulate tissue or to form lesions in tissue. 
     In the illustrated embodiment (shown in greater detail in  FIGS. 6 ,  7 , and  8 ), one function that the operative element  36  performs is to apply one or more treatment agents  20  to a targeted sphincter or adjoining tissue. The operative element  36  can be configured to apply the treatment agent in various ways. For example, the operative element  36  can apply the treatment agent directly to mucosal tissue overlying the sphincter. Alternatively, the operative element  36  can apply the treatment agent extrinsically to the sphincter through mucosal tissue overlying the sphincter. Still alternatively, the operative element  36  can inject the treatment agent into the sphincter. In combination with any of these application modalities, the operative element  36  can apply ablation energy in a selective fashion to a targeted tissue region, to create one or more lesions, or a prescribed pattern of lesions, below the mucosal surface. 
     In one treatment modality, the treatment agent  20  is selected from a class of agents that lead to a physical tightening of the sphincter, for example, a cytokine subtype or a tissue bulking agent, as already described. In this arrangement, the formation of lesions by the selective application of energy can incite a wound event, which interacts with the process of healing that the treatment agent initiated, to achieve the desired physiologic result. In another treatment modality, the treatment agent is selected from a class of agents that interrupt afferent nerve impulses that trigger transient sphincter relation, or that cause pain, or that otherwise contribute to the dysfunction, for example, a vanilloid compound, as already described. In this arrangement, the formation of lesions by the selective application of energy can result in the interruption of aberrant electrical pathways that may cause spontaneous sphincter relaxation. Further details of this treatment modality will be described later. 
     The treatment modalities can restore normal barrier function to the sphincter. 
     As  FIG. 5  shows, the treatment device  26  can operate as part of a system  24 . The system  24  includes an external treatment agent delivery apparatus  44 . A luer fitting  48  on the handle  28  couples to tubing  34  to connect the treatment device  26  to the treatment agent delivery apparatus  44 , to delivery the treatment agent for discharge by or near the operative element  36 . The system  24  can also include a generator  38  to supply energy to the operative element  36 , if formation of lesions to augment the treatment agent is desired. A cable  40  coupled to the handle  28  conveys the generated energy to the operative element  36 . 
     In the illustrated embodiment, the generator  38  supplies radiofrequency energy, e.g., having a frequency in the range of about 400 kHz to about 10 mHz. Of course, other forms of tissue ablation energy can be applied, e.g., coherent or incoherent light; heated or cooled fluid; resistive heating; microwave; ultrasound; a tissue ablation fluid; or cryogenic fluid. 
     The system  24  also desirably includes a controller  52 . The controller  52  is linked to the generator  38  and the treatment agent delivery apparatus  44 . The controller  52 , which preferably includes an onboard central processing unit, governs the power levels, cycles, and duration that the radio frequency energy is distributed to the operative element  36 , to achieve and maintain power levels appropriate to achieve the desired treatment objectives. In tandem, the controller  52  also desirably governs the delivery of the treatment agent. 
     The controller  52  desirably includes an input/output (I/O) device  54 . The I/O device  54  allows the physician to input control and processing variables, to enable the controller to generate appropriate command signals. 
     A. The Operative Element 
     In the embodiment shown in  FIGS. 6 to 8 , the operative element  36  comprises a three-dimensional basket  56 . The basket  56  includes one or more spines  58 , and typically includes from four to eight spines  58 , which are assembled together by a distal hub  60  and a proximal base  62 . In  FIGS. 6 to 8 , four spines  58  are shown, which are equally circumferentially spaced apart. 
     Each spine  58  preferably comprises a flexible body made, e.g. from molded plastic, stainless steel, or nickel titanium alloy. The cross sectional shape of the spine body  58  can vary, possessing, e.g., a circular, elliptical, square, or rectilinear shape. In the illustrated embodiment, the spine bodies  58  each possess a rectilinear shape to resist twisting. 
     In the illustrated embodiment (see  FIG. 9 ), each spine body  58  defines two or more interior lumens or passages. As  FIG. 9  shows, in the illustrated embodiment, three lumens or passages, designated L 1 , L 2 , and L 3 , are present. For each spine  58 , each passage L 1 , L 2 , and L 3  is dedicated to perform a different function. 
     In the illustrated embodiment (see  FIG. 10 ), a first or center passage L 1  carries a movable, elongated electrode element  66 . A second passage L 2  along one side the first passage L 1  carries a temperature sensing element  80 . A third passage L 3  along the opposite side of first passage L 1  is coupled to tubing  82  that carries the treatment agent from the treatment agent delivery device  44 . 
     1. The Electrodes 
     Each electrode  66  is carried within the first passage L 1  for sliding movement. Each electrode  66  slides from a retracted position, withdrawn in the spine  58  (as shown in  FIG. 7 ), and an extended position, extending outward from the spine  58  through an opening  84  in the spine  58  (as shown in  FIGS. 8 and 11 ). A push-pull lever  68  on the handle  28  (as  FIGS. 6 to 10  also show) controls the sliding movement of the electrodes with the spines  58  between the retracted position (by pulling rearward on the lever  68 ) and the extended position (by pushing forward on the lever  68 ). 
     As  FIGS. 6 to 8  show, the lever  68  is exposed on the handle  28  for manipulation by the thumb of an operator. A suitable ratchet assembly  118  (see  FIG. 6 ) may be provided to advance the sliding movement of the lever  68  in a controlled, stepwise fashion. A slot  119  on the handle  28  stops advancement of the lever  68  beyond a predetermined distance. 
     In the illustrated arrangement, the electrodes  66  are intended for monopolar operation. Each electrode  66  serves as a transmitter of energy, and an indifferent patch electrode on the patient=s skin (not shown) serves as a common return for all electrodes  66 . It should be appreciated, however, the operative element  36  could include bipolar pairs of electrodes  66 , if desired. 
     In the embodiment shown in  FIGS. 6 to 8 , an expandable structure  72  comprising, e.g., a balloon, is located within the basket  56 . The balloon structure  72  can be made, e.g., from a Polyethylene Terephthalate (PET) material, or a polyamide (non-compliant) material, or a radiation cross-linked polyethylene (semi-compliant) material, or a latex material, or a silicone material, or a C-Flex (highly compliant) material. Non-compliant materials offer the advantages of a predictable size and pressure feedback when inflated in contact with tissue. Compliant materials offer the advantages of variable sizes and shape conformance to adjacent tissue geometries. 
     The balloon structure  72  presents a normally, generally collapsed condition, as  FIG. 6  shows. In this condition, the basket  56  is also normally collapsed about the balloon structure  72 , presenting a low profile for deployment into the targeted tissue region. 
     The catheter tube  30  includes an interior lumen  94  (see  FIG. 7 ), which communicates with the interior of the balloon structure  72 . A fitting  76  (e.g., a syringe-activated check valve) is carried by the handle  28 . The fitting  76  communicates with the lumen. The fitting  76  couples the lumen  94  to a syringe  78  (see  FIG. 7 ), which injects fluid under pressure through the lumen  94  into the balloon structure  72 , causing its expansion, as  FIG. 7  shows. 
     Expansion of the balloon structure  72  urges the spines  58  of the basket  56  to open and expand (as  FIG. 7  shows). The force exerted by the balloon structure  72  upon the spines  58 , when expanded, is sufficient to exert an opening force upon the tissue surrounding the basket  56 . When moved to their extended positions, the electrode  66  penetrate tissue contacted by the spines  58 . 
     The electrodes  66  can be formed from various energy transmitting materials, e.g., nickel titanium, stainless steel (e.g., 304 stainless steel), or a combination of nickel titanium and stainless steel. The electrodes  66  have sufficient distal sharpness and strength to penetrate a desired depth into the smooth muscle of the targeted sphincter. The desired depth can range from about 4 mm to about 5 mm. 
     To further facilitate penetration and anchoring in the targeted tissue region, each electrode  66  is preferably biased with a bend (as  FIGS. 8 and 11  show). Movement of the electrode  66  into the spine  58  overcomes the bias and straightens the electrode  66  for passage through the lumen L 1 . An electrical insulating material (not shown) is desirably coated about the distal end of each electrode  66 , a distance below the distal tip. When the distal end of the electrode  66  that penetrates the targeted tissue region transmits radio frequency energy, the material insulates the surface of the tissue region from direct exposure to the radio frequency energy. 
     B. Application of The Treatment Agent 
     In the illustrated embodiment, the treatment agent delivery apparatus  44  conveys a selected treatment agent  20  through the third passage  13  in the spine  58  for discharge at the treatment site. The third passage  13  conveys the selected treatment agent from the apparatus  44  through an opening  120  formed in the spine  58 . The opening  120  in each spine  58  is generally aligned with the needle opening  84  in the spine  58  (see  FIG. 8 ), so that ablation and application of treatment agent  20  can occur in the same general tissue region. In this arrangement, the treatment agent can be applied either directly to mucosal tissue overlying the targeted sphincter, or extrinsically to the sphincter through mucosal tissue overlying the sphincter. 
     A given electrode  66  deployed by the operative device in a sphincter can also be used to inject the treatment agent  20  into the sphincter. In this arrangement, the electrode  66  includes an interior lumen  136  (see  FIG. 11 ). In this arrangement, the treatment agent delivery apparatus  44  is coupled to the lumen  136 . 
     C. Temperature Sensing 
     In the illustrated embodiment (see  FIGS. 10 and 11 ), the second passage  12  in each spine  58  carries a temperature sensing element  80 . In the illustrated embodiment, the temperature sensing element  80  comprises a thermocouple assembly. The temperature sensor is exposed through an opening  140  in the spine body  38 . The temperature sensor rests against surface tissue when the basket structure is deployed for use. Desirably (as  FIG. 11  shows), the temperature sensor opening  140  is generally aligned with the electrode and treatment agent openings  84  and  120 , so that ablation, temperature sensing, and application of treatment agent occur generally in the same localized tissue region. 
     III. Devices for the Treatment of Fecal Incontinence 
       FIGS. 12 and 13  show another tissue treatment device  302  well suited for injecting one or more treatment agents  20  in tissue regions at or near sphincter regions in the lower gastro-intestinal tract. More particularly, the device  302  is well suited for injecting the treatment agent  20  at or near the internal and/or external sphincter muscles in the anal canal to treat fecal incontinence. The device  302  is also well suited for applying radio frequency energy to these tissue regions, alone or in combination with injection of the treatment agent  20 , to form lesions. 
     As  FIGS. 12 and 13  show, the device  302  includes a hand grip  304  that carries an operative element  36   b . In the illustrated embodiment, the operative element  36   b  takes the form of a hollow, tubular barrel  306  made from a transparent, molded plastic material. The barrel  306  terminates with a blunt, rounded distal end  308  to aid passage of the barrel  306  through the anal canal, without need for a separate introducer. The hand grip  304  includes a viewing port  312  for looking into the transparent, hollow interior of the barrel  306 , to visualize surrounding tissue. 
     An array of needle electrodes  316  are movably contained in a side-by-side relationship along an arcuate segment of the barrel  306 . The needle electrodes  316  are mechanically linked to a finger-operated pull lever  318  on the hand grip  304 . By operation of the pull lever  318 , the distal ends of the needle electrodes  316  are moved between a retracted position ( FIG. 12 ) and an extended position ( FIG. 13 ). An electrical insulating material  344  is coated about the needle electrodes  316  (see  FIG. 13 ), except for a prescribed region of the distal ends, where radio frequency energy is applied to tissue. The generator  38  is coupled via the cable  10  to a connector  352 , to convey radio frequency energy to the electrodes  316 . 
     In use, the physician grasps the hand grip  304  and guides the barrel  306  into the anal canal  320 . The pull lever  318  is in the neutral position and not depressed, so the needle electrodes  316  occupy their normal retracted position, looking through the viewing port  312 , the physician visualizes the pectinate (dentate) line through the barrel  306 . Looking through the barrel  306 , the physician positions the distal ends of the needle electrodes  316  at a desired location above the pectinate (dentate) line. A fiberoptic can also be inserted into the barrel  306  to provide local illumination, or the physician can wear a headlamp for this purpose. Once the distal end of the barrel  306  is located at the targeted site, the physician depresses the pull lever  318 . The needle electrodes  316  advance to their extended positions. The distal ends of the electrodes  316  pierce and pass through the mucosal tissue into the muscle tissue of the target sphincter muscle. The distal end of the electrodes  316  can, e.g., penetrate the involuntary, internal sphincter muscle. The physician commands the controller  52  to apply radio frequency energy through the needle electrodes  316 . The energy can be applied simultaneously by all electrodes  316 , or in any desired sequence. 
     The treatment agent delivery apparatus  44  is coupled via tubing  12  to a connector  348  to convey the treatment agent  20 , e.g., through holes in the barrel  306 , to contact tissue at a localized position surrounding the electrodes  316 . In this arrangement, the treatment agent can be applied either directly to mucosal tissue overlying the targeted sphincter, or extrinsically to the sphincter through mucosal tissue overlying the sphincter. 
     Alternatively, one or more electrodes  316  deployed by the operative device in a sphincter can also be used to inject the treatment agent  20  into the sphincter. In this arrangement, the electrode  316  includes an interior lumen. In this arrangement, the treatment agent delivery apparatus  44  is coupled to the lumen  136 . 
     The barrel  306  (see  FIG. 13 ) also preferably carries temperature sensor  364 , one of which is associated with each needle electrode  316 . The sensors  364  sense tissue temperature conditions in the region adjacent to each needle electrode  316 . Preferably, the distal end of each needle electrode  316  also carries a temperature sensor  372  (see  FIG. 13 . 
     Further details of the construction and use of the device  26   b  and other devices that can be deployed to treat sphincter regions in the lower gastro-intestinal tract are disclosed in co-pending U.S. patent application Ser. No. 09/305,123, filed Apr. 21, 2000, and entitled “Systems and Methods for Treating Dysfunctions in the Intestines and Rectum,” which is incorporated herein by reference. 
     Various features of the invention are set forth in the following claims.