Abstract:
An intracorporeal marker includes a fibrous unitary marker body having bioabsorbable fibers compressed into a compressed configuration, and bound in the compressed configuration by a polymer binding agent. The intracorporeal marker may be incorporated into an intracorporeal marker delivery device having a delivery cannula which has a distal tip, an inner lumen and a discharge opening in communication with the inner lumen. The compression and binding occur prior to insertion of the fibrous unitary marker body into the inner lumen of the delivery cannula. The fibrous unitary marker body is slidably disposed within and pushable through the inner lumen of the elongated delivery cannula proximal to the discharge opening.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a continuation of U.S. patent application Ser. No. 10/444,770, filed May 23, 2003, entitled, “FIBROUS MARKER AND INTRACORPOREAL DELIVERY THEREOF”. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The invention is directed generally to a fibrous marker and devices and systems for the intracorporeal delivery thereof to a target site within a patient. 
       BACKGROUND OF THE INVENTION 
       [0003]    In diagnosing and treating certain medical conditions, it is often desirable to mark a suspicious body site for the subsequent taking of a biopsy, delivery of medicine, radiation, or other treatment, to mark a location from which a biopsy was taken, or at which some other procedure was performed. As is known, obtaining a tissue sample by biopsy and the subsequent examination are typically employed in the diagnosis of cancers and other malignant tumors, or to confirm that a suspected lesion or tumor is not malignant. The information obtained from these diagnostic tests and/or examinations is frequently used to devise a therapeutic plan for the appropriate surgical procedure or other course of treatment. 
         [0004]    In many instances, the suspicious tissue to be sampled is located in a subcutaneous site, such as inside a human breast. To minimize surgical intrusion into a patient&#39;s body, it is often desirable to insert a small instrument, such as a biopsy needle, into the body for extracting the biopsy specimen while imaging the procedure using fluoroscopy, ultrasonic imaging, x-rays, magnetic resonance imaging (MRI) or any other suitable form of imaging technique. Examination of tissue samples taken by biopsy is of particular significance in the diagnosis and treatment of breast cancer. In the ensuing discussion, the biopsy and treatment site described will generally be the human breast, although the invention is suitable for marking biopsy sites in other parts of the human and other mammalian body as well. 
         [0005]    Periodic physical examination of the breasts and mammography are important for early detection of potentially cancerous lesions. In mammography, the breast is compressed between two plates while specialized x-ray images are taken. If an abnormal mass in the breast is found by physical examination or mammography, ultrasound may be used to determine whether the mass is a solid tumor or a fluid-filled cyst. Solid masses are usually subjected to some type of tissue biopsy to determine if the mass is cancerous. 
         [0006]    If a solid mass or lesion is large enough to be palpable, a tissue specimen can be removed from the mass by a variety of techniques, including but not limited to open surgical biopsy, a technique known as Fine Needle Aspiration Biopsy (FNAB) and instruments characterized as “vacuum assisted large core biopsy devices”. 
         [0007]    If a solid mass of the breast is small and non-palpable (e.g., the type typically discovered through mammography), a biopsy procedure known as stereotactic needle biopsy may be used. In performing a stereotactic needle biopsy of a breast, the patient lies on a special biopsy table with her breast compressed between the plates of a mammography apparatus and two separate x-rays or digital video views are taken from two different points of view. With the assistance of a clinician, a computer calculates the exact position of the lesion in the breast. Thereafter, a mechanical stereotactic apparatus is programmed with the coordinates and depth information calculated by the computer and such apparatus is used to precisely advance the biopsy needle into the lesion. Depending on the type of biopsy needle(s) used, this stereotactic technique may be used to obtain histologic specimens e.g., obtained through coring needle biopsy or, more commonly, a biopsy with a vacuum assisted large core biopsy device. Usually at least five separate biopsy specimens are obtained at or around the lesion. 
         [0008]    The available treatment options for cancerous lesions of the breast include various degrees of lumpectomy or mastectomy and radiation therapy, as well as chemotherapy and combinations of these treatments. However, radiographically visible tissue features, originally observed in a mammogram, may be removed, altered or obscured by the biopsy procedure, and may heal or otherwise become altered following the biopsy. In order for the surgeon or radiation oncologist to direct surgical or radiation treatment to the precise location of the breast lesion several days or weeks after the biopsy procedure was performed, it is desirable that a biopsy site marker be placed in or on the patient&#39;s body to serve as a landmark for subsequent location of the lesion site. A biopsy site marker may be a permanent marker (e.g., a metal marker visible under X-ray examination), or a temporary marker (e.g., a bioresorbable marker detectable with ultrasound). While current radiographic type markers may persist at the biopsy site, an additional mammography generally must be performed at the time of follow up treatment or surgery in order to locate the site of the previous surgery or biopsy. In addition, once the site of the previous procedure is located using mammography, the site must usually be marked with a location wire which has a hook on the end which is advanced into site of the previous procedure. The hook is meant to fix the tip of the location wire with respect to the site of the previous procedure so that the patient can then be removed from the confinement of the mammography apparatus and the follow-up procedure performed. However, as the patient is removed from the mammography apparatus, or otherwise transported the position of the location wire can change or shift in relation to the site of the previous procedure. This, in turn, can result in follow-up treatments being misdirected to an undesired portion of the patient&#39;s tissue. 
         [0009]    As an alternative or adjunct to radiographic imaging, ultrasonic imaging and visualization techniques (herein abbreviated as “USI”) can be used to image the tissue of interest at the site of interest during a surgical or biopsy procedure or follow-up procedure. USI is capable of providing precise location and imaging of suspicious tissue, surrounding tissue and biopsy instruments within the patient&#39;s body during a procedure. Such imaging facilitates accurate and controllable removal or sampling of the suspicious tissue so as to minimize trauma to surrounding healthy tissue. 
         [0010]    For example, during a breast biopsy procedure, the biopsy device is often imaged with USI while the device is being inserted into the patient&#39;s breast and activated to remove a sample of suspicious breast tissue. As USI is often used to image tissue during follow-up treatment, it may be desirable to have a marker, similar to the radiographic markers discussed above, which can be placed in a patient&#39;s body at the site of a surgical procedure and which are visible using USI. Such a marker enables a follow-up procedure to be performed without the need for traditional radiographic mammography imaging which, as discussed above, can be subject to inaccuracies as a result of shifting of the location wire as well as being tedious and uncomfortable for the patient. 
         [0011]    Placement of a marker or multiple markers at a location within a patient&#39;s body requires delivery devices capable of holding markers within the device until the device is properly situated within a breast or other body location. Accordingly, devices and methods for retaining markers within a marker delivery device while allowing their expulsion from the devices at desired intracorporeal locations are desired. 
       SUMMARY OF THE INVENTION 
       [0012]    The invention is directed to a fibrous, swellable marker which positions a long-term radiographically detectable marker element within a target site of a patient&#39;s body. Preferably, short term ultrasound detectable markers are also delivered into the target site along with the fibrous marker. 
         [0013]    The fibrous marker embodying features of the invention is formed at least in part of a fibrous material, such as oxidized, regenerated cellulose, polylactic acid, a copolymer of polylactic acid and glycolic acid, polycaprolactone, in a felt and/or fabric or woven structure. The fibrous marker material is swellable in the presence of body fluid, such as blood or plasma, or other water based fluid. The fibrous material is formed into an elongated member and bound in a compressed condition to provide sufficient column strength to facilitate introduction into and discharge from a tubular delivery device. Suitable binding agents for holding the fibrous marker in a compressed condition are water soluble polymers such as polyvinyl alcohol, polyethylene glycol, polyvinyl pyrollidone. One or more radiographically detectable marker elements are provided with the fibrous marker, preferably centrally located, to ensure that the radiographically detectable element is disposed at a more or less central location within the target site rather than at a site margin. 
         [0014]    The one or more short term ultrasonically detectable markers, which are preferably delivered with the fibrous markers, are formed of bioabsorbable materials. Details of suitable short term ultrasonically detectable markers can be found in U.S. Pat. No. 6,161,034, issued Dec. 12, 2000, U.S. Pat. No. 6,347,241, issued Feb. 12, 2002, application Ser. No. 09/717,909, filed Nov. 20, 2000, now U.S. Pat. No. 6,725,083, and application Ser. No. 10/124,757, filed Apr. 16, 2002, now U.S. Pat. No. 6,862,470. These patents and applications are assigned to the present assignee and are incorporated herein in their entirety by reference. 
         [0015]    Marker delivery systems embodying features of the invention include an elongated cannula with an inner lumen extending therein and a discharge opening or port in a distal portion of the cannula which is in fluid communication with the inner lumen. The fibrous marker embodying features of the invention is slidably disposed within the inner lumen of the cannula, preferably along with at least one short term marker. The short term marker is preferably disposed distal to the fibrous marker so that upon discharge from the cannula into a target site cavity, the fibrous marker will swell upon contact with body fluids to block the accessing passageway. The discharge opening of the delivery device is preferably closed with a plug to hold in the markers during handling and delivery and to prevent tissue and fluid from entering the inner lumen through the discharge opening during delivery. Any water based fluid which may enter into the inner lumen of the delivery device can result in the expansion or swelling of the marker bodies within the inner lumen and prevent their deployment. Preferably, the plug is formed of a water swellable material, so that the plug occludes the opening upon contact with a water based fluid and thereby prevents the premature expansion of the markers within the inner lumen. The plug is easily pushed out of the discharge opening of the tubular delivery device. 
         [0016]    A movable plunger is slidably disposed within the inner lumen of the delivery cannula from an initial position accommodating the marker or markers and the plug within the tube, to a delivery position to push a marker against the plug to push the plug out of the discharge opening and to then eject one or more markers through the opening into the target tissue site. 
         [0017]    Upon being discharged into the intracorporeal target site, the fibrous marker swells on contact with body fluid, e.g. blood. The expanded fibrous marker fills or partially fills the cavity at the target site, positioning the radiopaque marker element within the interior of the target cavity. Additionally, a therapeutic agent, a diagnostic agent or other bioactive agent may be incorporated into the fibrous marker body. Such agents include a hemostatic agent to accelerate thrombus formation within the target cavity, an anesthetic agent, a coloring agent, an antibiotic agent, an antifungal agent, an antiviral agent, a chemotherapeutic agent, a radioactive agent and the like. 
         [0018]    The plug secures the discharge opening on the distal portion of the cannula, but it is easily ejected or removed from the orifice, allowing the delivery of the markers to a desired site within a patient&#39;s body. The plug or the cannula itself may have retaining features, such as recesses, protuberances, detents and the like which are configured to releasably retain the plug or the short term markers proximal to the plug until ejection of the plug from the delivery tube is desired. The retaining features may be complementary pairs, such as a plug protuberance configured to fit into a recess in the cannula interior. For further plug details see application Ser. No. 10/174,401, filed on Jun. 17, 2002, now U.S. Pat. No. 7,651,505, entitled Plugged Tip Delivery Tube For Marker Placement. This application is assigned to the present assignee and is incorporated herein in its entirety by reference. 
         [0019]    The invention, in one form thereof, is directed to an intracorporeal marker including a fibrous unitary marker body having bioabsorbable fibers compressed into a compressed configuration, and bound in the compressed configuration by a polymer binding agent. 
         [0020]    The invention, in another form thereof, is directed to an intracorporeal marker comprising a fibrous unitary marker body configured as a roll of bioabsorbable fiber material having at least one wrap. 
         [0021]    The invention, in another form thereof, is directed to an intracorporeal marker delivery device. The intracorporeal marker delivery device includes a delivery cannula which has a distal tip, an inner lumen and a discharge opening in communication with the inner lumen. A fibrous unitary marker body includes bioabsorbable fibers compressed into a compressed configuration and bound in the compressed configuration by a binding agent prior to insertion into the inner lumen of the delivery cannula. The fibrous unitary marker body is slidably disposed within and pushable through the inner lumen of the elongated delivery cannula proximal to the discharge opening. 
         [0022]    The invention provides the advantages of a relatively long term fibrous marker which is easily deployed into a target site and which positions a permanent radiographically detectable marker element within a central portion of the target site. When combined with short term ultrasound markers, the target site is easily detected at a later date by personnel with minimal training. These and other advantages of the invention will become more apparent from the following description when taken in conjunction with the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0023]      FIG. 1A  is a partly cut-away perspective view of a marker delivery assembly showing a fibrous marker embodying features of the invention and several short term markers within a marker delivery device and a plug embodying occluding the discharge opening of the delivery device. 
           [0024]      FIG. 1B  is a transverse cross-sectional view of the marker delivery assembly of  FIG. 1A  taken at line  1 B- 1 B. 
           [0025]      FIG. 1C  is a transverse cross-sectional view of the marker delivery assembly of  FIG. 1A  taken at line  1 C- 1 C. 
           [0026]      FIGS. 2A-2F  schematically illustrate the manufacture and use of a fibrous marker embodying features of the invention. 
           [0027]      FIG. 3  is a partially cut away, perspective view of a human breast having a biopsy cavity from which a biopsy specimen has been removed, and showing the delivery of a marker to the cavity. 
           [0028]      FIG. 4  schematically illustrates the deployment of a plurality of markers, including a marker embodying features of the invention, into a biopsy cavity. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0029]    A marker delivery assembly  10  embodying features of the invention and illustrated in  FIGS. 1A-1C , includes a marker delivery cannula  11  which has an inner lumen  12 , a plunger  13  slidably disposed within the inner lumen  12 , a fibrous marker  14  and a plurality of short term ultrasonically detectable markers  15  slidably disposed within the inner lumen, and a plug  16  occluding a discharge opening  17  in the distal portion of the cannula  11 . The delivery cannula  11  has an elongated shaft  18  which defines at least in part the inner lumen  12  and has a handle  20  on the proximal end of the cannula shaft  18  to facilitate handling and advancement of the device. The plunger  13  has a plunger shaft  21  and a plunger handle  22  to facilitate advancement of the plunger shaft  21  within inner lumen  12  of cannula  11  to discharge markers  14  and  15  from the discharge opening  17  in the cannula. As shown a plurality of short term ultrasonically detectable markers  15  are disposed within the inner lumen  12  distal to the fibrous marker  14 . The cannula  11  has a sharp, tissue penetrating distal tip  23  to facilitate advancement through tissue to the target site within the patient. A ramp  24  within the discharge opening  17  of the cannula  11  is provided to guide the markers  14  and  15  out through the discharge opening  17 . 
         [0030]    The manufacture and use of fibrous marker  14  is schematically illustrated in  FIGS. 2A-2F . A felt pad or mat  31  of oxidized, regenerated cellulose about 0.125 to about 0.375 inch (3.2-9.3 mm), preferably about 0.25 inch (6.4 mm) thick is compressed and impregnated with a 10% (Wt.) polyethylene glycol in a 70% isopropyl alcohol solution to a mat about 0.03 to about 0.05 inch (0.76-1.3 mm) thick with a length of about 20 mm. A reduction in thickness of 80% or more may be suitable. The compressed mat  31  is cut up into elongated strips  32  with square or near square transverse cross-sectional shapes. The strips  32  are wrapped in a fabric  33  of oxidized regenerated cellulose about 5 to about 10 mm in width and about 20 mm in length, compressed and impregnated with a 10% PEG dispersion and then dried at elevated temperatures (e.g. about 70° F. to about 150° F.) to a diameter of about 0.065 inch (1.65 mm). The fabric  33  should make at least one, preferably two or more complete wraps about the strip  32 . The wrapped and compressed strip may then be cut to a desired length to form the fibrous marker  13 . Alternatively, the uncompressed mat  31 , the strip  32  and fiber wrap  33  may be provided at the desired length for the fibrous marker  13 . A radiographically detectable marker element  34  may be formed of a radiopaque material such as 316L stainless steel or titanium wire  35  (OD about 0.005-0.01 inch, 0.13-0.25 mm) may then be crimped about or embedded in a central portion (or other desired portion) of the marker  14 . The fibrous marker  14  is then ready for deployment. 
         [0031]    The delivery of the markers into the target site within a human patient is illustrated in  FIG. 3 . In this particular illustration, the biopsy specimen has already been removed leaving a cavity  40  with the patient&#39;s breast  41 . A guide cannula  42  remains in the patient from the biopsy procedure. Marker delivery assembly  10  is held by the handle  20  and the shaft  18  thereof containing the markers  14  and  15  is introduced into the inner lumen  44  of the guide cannula  42 . The delivery cannula  11  is advanced within the inner lumen  44  until the discharge opening  17  of the delivery cannula is disposed within the cavity  40 . The operator then presses the handle  22  on plunger  13  to eject markers  14  and  15  out the discharge opening  17 . The pressure on the markers  14  and  15  is sufficient to dislodge the plug  16  which closes off the discharge opening  17 . A ramp  24  provided in the discharge opening  17  ensures that the markers  14  and  15  and plug  16  are discharged from the delivery device into the biopsy cavity  40 . 
         [0032]    Once the markers  14  and  15  are disposed within the biopsy cavity  40 , the fibrous marker  14  begins to swell from the body fluids located in the biopsy cavity. The short term, markers  15  are preferably ejected first and the fibrous marker  14  ejected last. This allows the fibrous marker  14  to swell and unfurl so as to extend across a significant portion of the cavity  40 . With a radiographically detectable wire or clip holding a central portion of the marker  14  in a constricted condition, the marker expands into a bow-tie could also place clip/wire to allow full unrolling form rectangular mat shape, as shown in  FIG. 4 , to center the radiopaque marker element  34  within the cavity  40 . This expansion will also tend to block off the accessing passageway  43  leading to the cavity  40  to prevent excursions of the markers  14  or other elements back into the passageway  43  which can cause the physician to miss the biopsy site cavity on subsequent examination. The marker  14  is schematically illustrated in  FIG. 2F  as having felt layer  32  over the entire surface of fabric layer  33 . However, in a clinical setting the layer  32  will cover only a portion of the layer  33 . 
         [0033]    The fibrous marker is preferably formed of a felt and/or fiber material formed of oxidized regenerated cellulose. However, the fibrous marker may be formed of a bioabsorbable polymer such as polylactic acid, a co-polymer of polylactic acid and glycolic acid, polycaprolactone, collagen and mixtures thereof, including mixtures with oxidized regenerated cellulose. Suitable oxidized, regenerated cellulose includes SURGICEL™ from the Ethicon Division of Johnson &amp; Johnson or other suitably oxidized regenerated cellulose. The fibrous marker may be formed of naturally hemostatic materials such as oxidized, regenerated cellulose or a hemostatic agent such as collagen or gelatin may be incorporated into the fibrous material to provide the hemostasis upon contact with blood. A wide variety of other hemostatic agents may be incorporated into the marker. The thrombus formed by the hemostasis is formed very quickly to fill the cavity at the biopsy site and at least temporarily hold the markers  14  and  15  in position within the cavity. Anesthetic agents to control post procedure pain, chemotherapeutic agents to kill any residual neoplastic tissue, coloring agents (e.g. carbon black and methylene blue) for visual location of the biopsy site, may also be incorporated into the fibrous marker. 
         [0034]    The radiopaque marker element is preferably clamped about the exterior of the fibrous material. However, a suitable radiopaque marker may be incorporated or otherwise embedded into the fibrous material to facilitate the location of the marker element by the fibrous marker within the biopsy cavity. The fibrous marker is generally configured to be slidably disposed within the inner lumen of the delivery cannula, and before delivery is about 0.5 mm to about 12 mm, preferably about 1 to about 8 mm in diameter and about 5 to about 30 mm, preferably about 10 to about 25 mm in length. Upon contact with a body fluid or other water based fluid, the length of the fibrous marker remains about the same but the wrapped structure unfolds upon swelling to a width of about 5 to about 25 mm, usually about 10 to about 20 mm. With a radiopaque marker element clamped about a center portion of the wrapped fibrous marker, the fibrous marker expands into a generally bow-tie shape when exposed to body fluids. However, even though secured to the fibrous marker, the radiopaque marker element need not restrict the expansion of the fibrous marker. 
         [0035]    The short term marker, which is primarily designed for ultrasound detection over a period of several hours to several months, is preferably formed of a bioabsorbable material such as polylactic acid-glycolic acid copolymer. However, the short term marker may be formed of other bioabsorbable materials including polylactic acid and porcine gelatin. The short term marker materials are processed to include bubbles about 20 to about 1000 micrometers in diameter for ultrasound detection. The bubble formation is preferably formed by the addition of sodium bicarbonate, but air may be physically incorporated while mixing the bioabsorbable material. The life of a particular short term marker may be controlled by the molecular weight of the polymer material from which it is made, with the higher molecular weights providing longer marker life. Suitable short term markers include the GelMark, which is a gelatin based marker, and GelMark Ultra which is a polylactic acid-glycolic acid copolymer based marker, sold by the present assignee. See also U.S. Pat. No. 6,161,034, U.S. Pat. No. 6,427,081, U.S. Pat. No. 6,347,241 and application Ser. No. 09/717,909, filed on Nov. 20, 2000, now U.S. Pat. No. 6,725,083, and application Ser. No. 10/174,401, filed on Jun. 17, 2002, now U.S. Pat. No. 7,651,505, which are incorporated herein by reference in their entirety. The short term markers are configured to be slidably disposed within the inner lumen of the delivery cannula and generally are about 0.5 mm to about 12 mm, preferably about 1 to about 3 mm in diameter, typically about 1.5 mm, and about 1 to about 20 mm, preferably about 2.5 to about 15 mm in length. The short term markers are preferably shorter than the fibrous marker. 
         [0036]    The plug used to occlude the discharge opening of the delivery cannula may be formed of the same material as the short term marker and indeed may be employed as a short term marker itself. The plug is preferably formed of or coated with polyethylene glycol which readily hydrates in the presence of body fluids and which causes the plug to swell and occlude the discharge opening. This prevents premature contact between body fluids and the markers within the inner lumen of the delivery device which can cause the markers to swell in the lumen and prevent or retard their deployment to the target site. 
         [0037]    An operator may grasp a device handle  20  to guide the device  10  during insertion, and to steady the device  10  during depression of the plunger  13 . Insertion of a device  10  results in the placement of at least a portion of the device  10  adjacent a desired location. The device  10 , in particular the distal tip  23  and orifice  17  of the device  10 , may be guided adjacent a desired location such as a lesion site, or a biopsy cavity, or other internal body site where delivery of a marker  14  is desired. 
         [0038]    The short term marker typically should remain in place and be detectable within a patient for a period of at least 2 weeks to have practical clinical value, preferably at least about 6 weeks, and may remain detectable for a time period of up to about 20 weeks, more preferably for a time period of up to about 12 weeks. The fibrous marker should have a life period of short duration, e.g. less than 30 days but the radiographically detectable marker element of the fibrous marker should have a life of at least one year and preferably is permanently radiographically detectable. 
         [0039]    While stainless steel and titanium are preferred radiopaque materials, the radiopaque elements may be made of suitable radiopaque materials such as platinum, gold, iridium, tantalum, tungsten, silver, rhodium, nickel, NiTi alloy. MRI contrast agents such as gadolinium and gadolinium compounds, for example, are also suitable for use with plugs and/or markers embodying features of the invention. 
         [0040]    Marker delivery devices other than those shown in  FIGS. 1A-1C  may be employed. Other suitable delivery devices are depicted in U.S. Pat. No. 6,347,241 and application Ser. No. 09/717,909, now U.S. Pat. No. 6,725,083, which have been incorporated herein by reference. 
         [0041]    While particular forms of the invention have been illustrated and described herein, it will be apparent that various modifications and improvements can be made to the invention. Moreover, those skilled in the art will recognize that individual features of one embodiment of the invention can be combined with any or all the features of another embodiment. Accordingly, it is not intended that the invention be limited to the specific embodiments illustrated. It is therefore intended that this invention to be defined by the scope of the appended claims as broadly as the prior art will permit. 
         [0042]    Terms such a “element”, “member”, “device”, “sections”, “portion”, “section”, “steps” and words of similar import when used herein shall not be construed as invoking the provisions of 35 U.S.C. §112(6) unless the following claims expressly use the terms “means” or “step” followed by a particular function without specific structure or action. 
         [0043]    All patents and patent applications referred to above are hereby incorporated by reference in their entirety.