Abstract:
A tissue sample collection assembly collects undamaged cells from a tissue specimen comprising a damaged tissue layer at a margin thereof. The assembly includes a tissue-severing device used to separate at least a portion of the damaged tissue layer. The tissue-severing device may have a tissue-adhesive surface so that undamaged cells may contact and adhere to the tissue-adhesive surface for subsequent analysis. The assembly may comprise an apertured device comprising inner and outer surfaces with apertures passing therebetween. The apertures may be sized and shaped so that when the inner surface of the apertured device is pressed against a tissue specimen, portions of an undamaged tissue layer of the tissue specimen pass through the apertures and past the outer surface so that the tissue-severing device can sever the undamaged tissue layer portions from the remainder of the tissue specimen. Exposed undamaged tissue may adhere to a tissue-adhesive surface of the tissue-severing device.

Description:
CROSS-REFERENCE TO RELATED APPLICATION  
       [0001]    This application claims the benefit of provisional patent application No. 60/315,913 filed on Aug. 29, 2001 and entitled Diagnostic Apparatuses And Methods For Use. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    This invention relates to medical devices and methods, in particular apparatus and methods for the collection of undamaged tissue from a tissue specimen of the type having damaged tissue at the margin of the tissue specimen.  
           [0003]    To be able to analyze tissue intraoperatively, immediately postoperatively as well as postoperatively is extremely advantageous to the physician. This tissue analysis is often necessary for definitive surgical planning or other postoperative therapy or care.  
           [0004]    Cancer results in over 1,500 deaths every day in the U.S. (550,000 every year). Therapy modalities for cancer are plentiful and continued to be researched with vigor. Still, the preferred treatment continues to be physical removal of the cancer. When applicable, surgical removal is preferred (breast, colon, brain, lung, kidney, etc.). Open, excisional, surgical removal is often extremely invasive and efforts to remove cancerous tissue in a less invasive way continue, but have not yet been perfected.  
           [0005]    Still, the only cure for cancer continues to be early diagnosis and subsequent early treatment. As cancer therapies continue at an earlier stage of diagnosis, the cancerous tissue is smaller and smaller. Early removal of these smaller cancers demands new techniques for removal and obliteration that are less invasive than present techniques. Patent applications and patents assigned to Artemis Medical, Inc., as well as other technologies of such companies as SenoRx, Vivant Medical, NeoThermia, Sanarus, Calypso Medical, USSC, etc., describe percutaneous, potentially less traumatic tissue removal techniques. In the case of tissue removal from the breast (but this is often true for other tissue such as the variety of different types of sinuous tissue often found in plaque build up in arteries in the case of occlusive vascular disease), the tissue being removed is often difficult to cut and hence difficult to remove. See, for example, U.S. Pat. Nos. 6,270,464; 6,179,860; and 6,221,006; and International Publication No. WO 00/74561.  
           [0006]    There are many techniques available today, such as the USSC ABBI and the Site Select from Imagine Corporation that attempt to accomplish this but with results that leave the breast physician desiring. The Mammotome from J&amp;J and the MIBB from USSC also require large bore access to accomplish biopsy but only remove slivers of tissue. Further, as reported at the Mar. 13, 2000 symposium of the American Society of Surgical Oncologists (SSO) in New Orleans, Stereotactic Core Biopsy (SCB) such as those accomplished with the BARD TRU-CUT, Mammotome or MIBB (the Mammotome and MIBB are referred to as ‘vacuum assisted’ biopsy devices) fall short in providing definitive answers to detail precise surgical regimens after this SCB type biopsy, especially with DCIS (Ductal Carcinoma In Situ), LCIS (Lobular Carcinoma In Situ), ADH (Atypical Ductal Hyperplasia) and other discordant findings usually of early detected cancers or pre-cancerous lesions. In this study presented by Dr. Ollila et al from the University of North Carolina, Chapel Hill, the investigators discovered that there is evidence that histology and pathology is compromised due to the damage that is done by these conventional techniques. Hence for many reasons, the least of which is not that DCIS, LCIS and ADH are becoming more detectable and hence more prevalent in breast cancer diagnosis in the U.S., there is a growing need to improve upon these core (BARD TRU-CUT and others (Medi-Tech, Cook, MD Tech, etc.)), vacuum assisted core biopsy systems (Mammotome or MIBB) as well as the established large core biopsy systems (Site Select and ABBI). Hence these improved systems that realize a large, contiguous piece of tissue through a smaller puncture site as described above (Artemis, Vivant, SenoRx, NeoThermia, Sanarus, Calypso, etc.) yield many of the preferred characteristics that the physician needs and wants. However there are always trade-offs. As far as the inventors know, all of the aforementioned technologies that remove a large contiguous piece of tissue through a smaller cannula, as well as the ABBI that uses a large coring (20-40 mm) technology from the skin all the way to the suspect lesion (or cancer), utilize an external energy source to ‘sever’ or cut the tissue for removal because of the odd characteristics of breast tissue. The aforementioned external energy sources include, but are not limited to RF (Radio Frequency), electrocut or electrocautery, cryosurgical, mechanical (i.e. vibrational, ultrasonic, etc.), laser, etc.  
           [0007]    The trade-off with using these external energy sources is the fact that they tend to modify or damage tissue characteristics that may be detrimental to accurate or definitive tissue analysis. In the case of breast cancer this damaged tissue is detrimental to doing definitive pathological analysis of the cancer or suspect lesion. This analysis is often realized in a procedure known as ‘conization’. Conization is used in a procedure often referred to as a loop procedure. When a woman is presented with an atypicical pap smear of the cervix, the OB/GYN or other physician often refers her to this procedure. The physician usually uses an ‘electrocut loop’ device to trim off a small piece of the cervix for analysis. The energized loop often leaves what is referred to as an ‘electrocautery artifact’, that is a change of the tissue due to the electrical energy generated. The pathologist usually takes the removed cervical tissue sample and begins to analyze the tissue by cutting back from the area with the artifact. He/she removes small layers of tissue until reaching non-affected tissue (i.e. tissue with no electrocautery artifact). Upon reaching that tissue, if tissue is found with normal cells (not atypical cells), the patient is told that the conization was successful and no additional treatment/diagnosis/care is necessary until the next scheduled pap smear. If the pathologist finds atypical (not normal) cells then the patient is required to come back a few (or several) days later for additional conization or other treatment.  
           [0008]    In the case of breast cancer surgery, the patient is usually on the operating room table. The surgeon removes the cancerous tissue, hoping to ‘get it all’ by removing the cancer and healthy tissue known as ‘clean’ margins. There is significant controversy as to what defines ‘clean’ margins. Some physicians call ‘clean’ margins as one cell of ‘normal’ tissue between the cancerous tissue and the external surface of the removed tissue. Other physicians prefer to define clean margins as 10 mm of tissue between the cancer and the healthy tissue. Regardless of the controversy that exists on what constitutes clean margins, all physicians agree that they must know what the margin distance is. Certainly other criteria exist, but if margins are poor or good determines how the patient is followed. For example if no margins exist, most often additional tissue is removed via an additional surgical procedure. If margins are only fair, the physician may prefer to use an adjunctive therapy that is aggressive with no additional surgery. If margins are good, usually the physician will still prescribe additional adjunctive therapy, but not necessarily as aggressive as with only fair margins.  
           [0009]    Hence with the importance put upon margins, it would be extremely beneficial for the surgeon/physician to know if clean margins exist at the time of surgery. For example if they were to know, at the time of surgery, with the patient still on the operating room table, that there are bad margins (AKA ‘dirty margins’), the surgeon could re-enter the cavity where the cancerous tissue was removed and then remove additional tissue. This would allow the patient to have fewer surgeries and thus fewer potentially deleterious effects that accompany every surgical procedure. Such a deleterious effect could be as severe as death.  
           [0010]    Because of this important need of determining margins at the time of surgery, a technique known as ‘Touch Prep’ has been developed. Touch Prep refers to a preparation of the cancerous tissue that is removed and an immediate analysis of that tissue intraoperatively or immediately post operatively. Touch Prep can basically described as follows.  
           [0011]    Upon removal of the tissue from the patient, the surgeon marks the orientation of the tissue with respect to how it was removed from the body. This marking convention is different at each institution, but is usually done with the placement of sutures on the tissue removed. For example, the surgeon may place one suture on the anterior side; two sutures on the posterior side, three sutures on the medial side and the lateral side would be defined with no sutures.  
           [0012]    The tissue is then immediately sent to pathology where it is stained with various colors again using a convention in the particular institution that would indicate the orientation of how the tissue was removed from the patient (i.e. anterior, posterior, medial, lateral, etc.). This color staining allows the pathologist and the surgeon to communicate as to the condition of the margins on the tissue. The staining does not affect pathological analysis except for the fact that the pathologist knows which side of the tissue he/she is analyzing.  
           [0013]    At this point, the pathologist takes the tissue and smears tissue samples from the different colors onto ‘analyzing slides’ for immediate microscopic evaluation. As the pathologist is searching each individually ‘colored’ slide, he/she knows the particular orientation of where these cells came from in the patient. If the pathologist sees irregular or cancerous cells on a particular slide, he/she can then immediately notify the surgeon that there exist irregular margins on a particular side of the tissue sample removed.  
           [0014]    Once ‘irregular margins’ is communicated to the surgeon, re-intervention is usually accomplished. Because the surgeon knows that irregular margins exist on a particular side of the tissue removed, they are able to re-enter the cavity and remove additional tissue from the patient in that particular area.  
           [0015]    At that point, often, the Touch Prep is repeated again until ‘clean margins’ have been determined. This procedure allows the patient to usually have only one surgical intervention as opposed to doing analysis on the tissue post operatively and then having subsequent pathology only after the patient has left the operating room and thus requiring an additional surgical intervention with the accompanying risks.  
           [0016]    This new Touch Prep type of analysis is not completely perfect, but is becoming more commonplace due to the obvious advantages that come with it. However, with the addition of the new technologies described above, those being removal of tissue with external energy sources, the Touch Prep procedure can be compromised. If electro-cautery artifacts (or any type of damaged tissue for that matter) exist on the external sample of the tissue removed, this Touch Prep may be compromised.  
           [0017]    Further, many physicians are now beginning to use such a modification of the Touch Prep procedure at the time of biopsy so that determination of the biopsy sample is known immediately at the time of diagnosis during biopsy. For example, some physicians using a ‘core’ type technology may smear the cored tissue sample onto a pathology slide. The slide is then immediately taken to pathology so that a determination of the tissue can be at least partially accomplished immediately. The coloring or other orientation of the biopsy sample may or may not be done. In the case where it is not done, the orientation is not necessarily accomplished, but only whether cancer or other irregularity exists. In either case it allows the physician immediate determination of whether irregular cells exist instead of waiting the usual day or more for said analysis.  
         SUMMARY OF THE INVENTION  
         [0018]    The present invention relates to the analysis of undamaged tissue from a tissue specimen in which some of the tissue at the margin of the tissue sample may have been damaged during removal procedures, such as electrocautery (RF or other electrosurgical apparatus), mechanical cutting using wire and scalpel-like devices, vibrational devices, cryogenic procedures, thermal procedures, and compression techniques.  
           [0019]    A first aspect of the invention is directed to a tissue sample collection assembly, for collecting undamaged cells from a tissue specimen, comprising a reference surface placeable against a tissue specimen, the tissue specimen comprising a damaged tissue layer at a margin of the tissue specimen, the damaged tissue layer having a first, expected thickness. The assembly also includes a tissue-severing device spaced apart from the reference surface by a second distance, the second distance being at most about 40% greater than the first thickness. The tissue-severing device may be used to separate at least a portion of the damaged tissue layer of the tissue specimen so that undamaged cells may be analyzed. The tissue-severing device may have a tissue-adhesive surface facing the reference surface so that undamaged cells may contact and adhere to the tissue-adhesive surface. The tissue-severing device and the reference surface may be fixed or movable relative to one another.  
           [0020]    A second aspect of the invention is directed to a tissue sample collection assembly, for collecting undamaged cells from a tissue specimen, comprising a reference surface placeable against a tissue specimen, the tissue specimen comprising a damaged tissue layer at a margin of the tissue specimen, the damaged tissue layer having a first, expected thickness. The assembly also includes a tissue-severing device spaced apart from the reference surface by a second distance, said second distance chosen to be at least as great as the first thickness. The tissue-severing device has a tissue-adhesive surface facing the reference surface. The tissue-severing device may be used to separate at least a portion of the damaged tissue layer of the tissue specimen so that undamaged cells may contact and adhere to the tissue-adhesive surface. The tissue-severing device and the reference surface may be fixed or movable relative to one another.  
           [0021]    A third aspect of the invention is directed to a tissue sample collection assembly, for collecting undamaged cells from beneath a damaged tissue layer at a margin of a tissue specimen, the damaged tissue layer having a first thickness. The assembly comprises an apertured device comprising inner and outer surfaces with apertures passing therebetween and a tissue-severing device having a tissue-adhesive surface placeable adjacent to the outer surface. The apertures are sized and shaped so that when the inner surface of the apertured device is pressed against a tissue specimen, portions of an undamaged tissue layer of the tissue specimen pass through the apertures and past the outer surface so that the tissue-severing device can sever the undamaged tissue layer portions from the remainder of the tissue specimen. Exposed undamaged tissue may adhere to the tissue-adhesive surface of the tissue-severing device.  
           [0022]    A fourth aspect of the invention is directed to method for analyzing undamaged tissue from a margin of a tissue specimen of a type in which the margin comprises a damaged tissue layer overlying undamaged tissue, said damaged tissue layer comprising damaged tissue. The expected thickness of the damaged tissue is determined. The thickness of the damaged tissue to be removed is chosen, the chosen thickness being greater than the expected thickness. At least a portion of the damaged tissue layer is removed to expose a region of the undamaged tissue. Tissue from at least a chosen one of the undamaged tissue region and the inner surface of the portion of the damaged tissue region is analyzed. The chosen thickness is minimized to help ensure that the tissue analyzed is close to the margin of the tissue specimen to help with the determination of whether there is tissue of interest at the margin. The removing step may comprise pressing an apertured device and the damaged tissue layer against one another causing damaged tissue to protrude through one or more apertures, and separating at least some of the protruding damaged tissue from the remainder of the tissue specimen to expose the region of undamaged tissue. The separating step may comprise passing a blade over the apertured device. The apertured device may comprise a generally tubular braided device. The removing step may also comprise passing a tissue-separating tool over the damaged tissue layer; the passing step may comprise adhering tissue from the undamaged tissue region to a tissue sample region of the tissue-separating tool.  
           [0023]    A fifth aspect of the invention is directed to method for analyzing undamaged tissue from a margin of a tissue specimen of a type in which the margin comprises a damaged tissue layer overlying undamaged tissue, said damaged tissue layer comprising damaged tissue. A tissue sample is removed from the margin of the tissue specimen, the tissue sample comprising damaged tissue and undamaged tissue. An analysis technique that differentiates between damaged tissue and undamaged tissue in a tissue sample is chosen. Undamaged tissue from the tissue sample is analyzed. The analyzing step may be carried out using, for example, at least one of magnetic resonance imaging (MRI), ultrasound (US), positron emission tomography (PET), computed tomography (CT), X-ray, photo-spectral analysis and electron microscopic analysis.  
           [0024]    A sixth aspect of the invention is directed to method for analyzing undamaged tissue from a margin of a tissue specimen of a type in which the margin comprises a damaged tissue layer overlying undamaged tissue, said damaged tissue layer comprising damaged tissue. A tissue sampling device is inserted into the damaged tissue layer and through damaged tissue to access undamaged tissue. An undamaged tissue sample is captured using the tissue sampling device. The undamaged tissue sample is removed from the tissue specimen. The undamaged tissue sample is analyzed.  
           [0025]    A seventh aspect of the invention is directed to method for analyzing undamaged tissue from a margin of a tissue specimen of a type in which the margin comprises a damaged tissue layer overlying undamaged tissue, said damaged tissue layer comprising damaged tissue. A tissue characteristic analysis probe is inserted into the damaged tissue layer and through damaged tissue to access undamaged tissue. The undamaged tissue is analyzed for said tissue characteristic using the tissue characteristic analysis probe.  
           [0026]    An eighth aspect of the invention is directed to method for obtaining a tissue analysis sample following removal of a tissue specimen through an access track of a patient, the access track opening into a tissue specimen excision void of the patient. A sample retrieval structure, movable between a collapsed state an expanded state, is selected. The sample retrieval structure has a tissue-adhesive surface. The sample retrieval structure, in a collapsed state, is inserted along an access track and into an excision void of a patient. The sample retrieval structure is expanded to an expanded state. The tissue-adhesive surface is pressed against a wall defining the excision void thereby causing tissue from said wall to adhere to the tissue-adhesive surface. The sample retrieval structure is collapsed to a collapsed state. The sample retrieval structure, together with tissue adhering to the tissue-adhesive surface, is removed from the patient, whereby said tissue adhering to the tissue-adhesive surface may be analyzed.  
           [0027]    Various advantages may arise from the various aspects of the invention. For example, one advantage may be the controlled removal of the damaged tissue layer from the tissue specimen so that Touch Prep can still be accomplished. Another advantage is that the tissue just beneath the damaged tissue can be analyzed so that margin and/or tissue quality can be determined. The invention may be carried out in a safe and cost-effective manner. The invention may also be made to be simple to use and in a very real sense simple to understand. This will encourage its adoption and use by medical personnel. The invention generally relates to procedures with which the medical profession is familiar so that the skills that have been learned from previous experience will continue to have applicability.  
           [0028]    Other features and advantages of the invention will appear from the following description in which preferred embodiments have been discussed and detail in conjunction with the accompanying drawings. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0029]    [0029]FIG. 1 illustrates a conventional tissue specimen after removal from the patient&#39;s body, the tissue specimen having orientation sutures placed thereon by the surgeon;  
         [0030]    [0030]FIG. 2 illustrate the removal of a portion of damaged tissue from the margin of a tissue specimen by a skiving tool;  
         [0031]    [0031]FIG. 3 is a front elevational view of the skiving tool of FIG. 2;  
         [0032]    [0032]FIG. 4 is an enlarged perspective view illustrating the removable double-adhesive-sided tape on the blade of the skiving tool of FIG. 3;  
         [0033]    [0033]FIG. 5 is a front elevational view of a multiple bladed skiving tool;  
         [0034]    [0034]FIG. 6 is a simplified cross-sectional view of a sample collection assembly made according to the invention, shown adjacent the tissue specimen, having a blade offset from a reference surface for the removal of a predetermined thickness of tissue from the tissue specimen;  
         [0035]    [0035]FIG. 7 illustrates an alternative embodiment of the sample collection assembly of FIG. 6 in which the reference surface is a vacuum surface and the blade can move relative to the reference surface;  
         [0036]    [0036]FIG. 8 illustrates a stiff, single aperture device being pressed against a tissue specimen prior to moving a blade across the single aperture device to slice off protruding damaged tissue from the margin of the tissue specimen so to expose undamaged tissue;  
         [0037]    [0037]FIG. 9 illustrates an alternative embodiment of the device of FIG. 8 including a stiff, multiple aperture device used in conjunction with a blade;  
         [0038]    [0038]FIGS. 10 and 11 illustrate a further alternative embodiment in which a motorized skiving tool includes an apertured mesh, which is pressed against a tissue specimen, and a rotatable blade, which slices protruding damaged tissue from a tissue specimen;  
         [0039]    [0039]FIG. 12 shows the tissue specimen of FIG. 11 after the protruding damaged tissue has been sliced away leaving exposed undamaged tissue regions;  
         [0040]    [0040]FIG. 13 illustrates a generally tubular braided device and a tissue specimen to be placed into the generally tubular braided device;  
         [0041]    [0041]FIG. 14 illustrates the generally tubular braided device of FIG. 13 with the tissue specimen therein, the braided device having been placed in tension causing tissue to protrude through the apertures of the braided device to permit a blade or other tissue separating or removing device to cut or slice off or otherwise remove the protruding damaged tissue;  
         [0042]    [0042]FIG. 14A is an enlarged view of a portion of FIG. 14 illustrating the tissue protruding through the apertures formed between the fibers of the braided device;  
         [0043]    [0043]FIG. 15 shows a specimen capturing and removal device having a tissue specimen captured within the interior of a two layer braided device;  
         [0044]    [0044]FIG. 16 is a simplified enlarged cross-sectional view taken a long line  16 - 16  of FIG. 15 showing an outer, tissue-impervious tubular braided device connected to and extending from an inner, tubular braided device with apertures, the inner, tubular braided device being similar to the braided device of FIGS. 13 and 14;  
         [0045]    [0045]FIG. 17 shows the device of FIG. 15 after the outer braided device has been separated from the placement shaft and pulled back over the inner braided device so that placing the braided device in tension causes damaged tissue to protrude out through the apertures formed between the fibers of the inner braided device in a manner similar to the embodiment of FIG. 14;  
         [0046]    [0046]FIGS. 18 and 19 illustrate a closed end braided device containing a tissue specimen and a generally cylindrical blade moving over the exterior of the braided device causing protruding damaged tissue from the margin of the tissue specimen to be sliced off or severed so to expose undamaged tissue;  
         [0047]    [0047]FIG. 20 illustrates a coiled, generally cylindrical blade which permits the transverse dimensions of the blade to be adjusted according to the transverse dimension of the tissue specimen within the braided device of FIGS. 18 and 19;  
         [0048]    [0048]FIG. 21 shows a tissue specimen being placed in an open-ended container;  
         [0049]    [0049]FIG. 22 shows the specimen of FIG. 21 housed within the container and a cutting device being driven into the container;  
         [0050]    [0050]FIG. 23 illustrates a specimen of FIG. 22 after the cutting device has sliced away a major portion of the damaged tissue layer lying against the inner wall of the container;  
         [0051]    FIGS.  24 - 26 A illustrate obtaining undamaged tissue from a cavity using a void wall tissue sample collection assembly comprising a radially expandable and contractible apertured void wall engagement device and a blade movable along the inner surface of the void wall engagement device to remove tissue protruding through the apertures thereof to expose undamaged tissue regions;  
         [0052]    [0052]FIG. 27 illustrates a needle type tissue removal technology (not dissimilar to FNA (Fine Needle Aspiration)) where a stop on the device is used so that tissue cell sampling can be precisely taken just below the damaged external tissue layer; and  
         [0053]    [0053]FIG. 28 illustrates two tissue characteristic analysis devices, one having multiple tissue characteristic analysis probes and the other having a single tissue characteristic analysis probe, each having a stop so that the probes may be accurately placed to a certain depth just below the damaged tissue layer for the analysis of one or more tissue characteristics. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0054]    [0054]FIG. 1 is an illustration of a conventional tissue specimen  10  that has been removed from the body in a condition that it can be analyzed from a histological/pathological perspective immediately upon removal so that should additional tissue removal or other therapy be required then immediately after analysis of the tissue, this can be accomplished. A variety of analytic tools could be used to determine tissue characteristics. These tools include, but are not limited to the use of a computerized fiber-optic and/or laser technology, microscopic spectrometer to analyze protein density, flow cytometry, instant mitotic index, or instant immunohistochemistry to assess whether cells on the margin of the specimen are malignant or not would determine if the excised specimen contained all of the tumor or if some had been left behind and/or if sufficient margins exist, FNA (fine needle aspiration), skiving of the tissue for Touch Prep analysis, impedance testing of the tissue, resistance or other electrical measurement, density, reflectivity, refractivity, etc. In FIG. 1, you can see 1, 2 and then 3 orientation sutures  12  that have been placed by the surgeon to orient the tissue with the patient&#39;s body.  
         [0055]    [0055]FIGS. 2, 3 and  4  illustrate a first embodiment of a tissue sample collection assembly  14 , in particular a skiving (tissue-separating) tool  14 , comprising a blade  16  positioned adjacent to an opening  18  formed in the body  20  of skiving tool  14 . Blade  16  has a tissue-severing edge  22 . Tissue specimen  10  has a margin  24  comprising a layer of tissue that may have been iatrogenically damaged due to energy used to remove tissue specimen  10  originally. Skiving tool  14  is used to remove a portion  26  of the damaged tissue layer to expose an undamaged tissue region  28 . It should be noted that the thickness of portion  26  of the damaged tissue layer is chosen according to the expected thickness of the damaged tissue. In some cases the thickness of the damaged tissue will only be about 0.20 mm. The thickness of portion  26  can be controlled by, for example, controlling the compression force exerted on tissue sample  10  and the distance between edge  22  and a reference surface  30  of body  20  of skiving tool  14 .  
         [0056]    It will usually be desired to choose the thickness of portion  26  to be as small as possible while still exposing undamaged tissue region  28 . This will help to ensure that the undamaged tissue analyzed is as close to margin  24  of tissue specimen  10  has possible to help with the determination of whether there are cancer, or other cells of interest, at the margin. Therefore, it is preferred that the thickness of portion  26  be about 40% greater, and preferably about 20% greater, and most preferably about 10% greater than the expected thickness of the damaged tissue layer. Also, it should be understood that undamaged tissue can be obtained from undamaged tissue region  28  as well as the underside  32  of portion  26 . Skiving tool  14  may be designed to allow for the small incremental removal of damaged tissue rather than removal of the entire damaged tissue layer in a single pass.  
         [0057]    The embodiment of FIGS.  2 - 4  obtains undamaged tissue from underside  32  of portion  26  by the use of a removable, double-adhesive-sided tape  34  on the inner surface  38  of blade  16 , which passes against underside  32 . After removal of portion  26 , tape  34  is removed, as suggested in FIG. 4, and the undamaged tissue adhering to adhesive service  36  may be marked, indicating where on tissue specimen  10  the undamaged tissue was obtained from, and then analyzed. Adhesive surface  36  may be provided in other manners. For example, inner surface  38  may be made so that undamaged tissue adheres directly to surface  38 ; this may be achieved by, for example, providing surface  38  with a suitable texture or roughness to collect tissue or coating surface  38  with a suitable adhesive. Also, blade  16  may be removable from body  20  to facilitate tissue analysis. Blade  16  may also be made to be of a translucent or transparent material to facilitate visual inspection of the removed tissue without the need to transfer the remove tissue from blade  16  to, for example, an analyzing slide. Additional embodiments and aspects of the invention are discussed below with like reference numerals referring to like elements.  
         [0058]    [0058]FIG. 5 illustrates a multiple bladed skiving tool  40 . Tool  40  is similar to tool  14  but has a number of curved blades  42 , each blade having a curved edge  44 .  
         [0059]    [0059]FIG. 6 illustrates another embodiment of a sample collection assembly  46  in which a blade  16  is used as the tissue-severing device, blade  16  being affixed to body  20  and oriented parallel to reference surface  30 . Blade  16  is spaced apart from reference surface  30  by an offset  48 , offset  48  being chosen to be at least slightly greater than the expected thickness of the damaged tissue. A portion  26  of tissue specimen  10  is separated from the remainder of the tissue specimen and is captured within the space  50  defined between reference surface  30  and tissue-adhesive surface  36 .  
         [0060]    [0060]FIG. 7 illustrates a further embodiment of a sample collection assembly  52  similar to the embodiment of FIG. 6. However, assembly  52  comprises a tissue contact surface  54  defining a number of vacuum ports  56 , the vacuum ports coupled to a vacuum source  58 . As suggested in FIG. 7, the margin  24  of specimen  10  is pulled into contact with surface  54  because of the suction forces created at vacuum ports  56 . Assembly  52  also comprises a movable blade  60  connected to body  62  of assembly  52  by a slide coupling  64  to permit tissue at surface  54  to be cut or separated from the remainder of specimen  10 . If desired, after the removal of the severed tissue at surface  54 , the newly exposed tissue could be placed against surface  54  and blade  60  used to slice off a second tissue sample of undamaged cells for analysis.  
         [0061]    [0061]FIG. 8 illustrates a stiff, single aperture device  66  being pressed against a tissue specimen  10  prior to moving a blade  68  across outer surface  70  of device  66  to slice off protruding damaged tissue  72  from margin  24  of the tissue specimen so to expose undamaged tissue. As in the above embodiments, undamaged tissue may be collected, for example, from an adhesive surface on the underside of blade  68  or from the undamaged tissue region created by removing protruding damaged tissue  72 . FIG. 9 illustrates an alternative to the embodiment of FIG. 8 comprising a stiff, multiple aperture device  74  which permits protruding damaged tissue  72  to be created at each aperture and then removed by blade  68 . Alternatively, protruding damaged tissue  72  could be removed using sandpaper, a rasp or other suitable structures or techniques. The size of the apertures and the force exerted on tissue specimen  10  largely determines how much tissue is pushed up through the apertures.  
         [0062]    [0062]FIGS. 10 and 11 illustrates a further sample collection assembly  76  in the form of a motorized skiving tool  76 , comprising a hand-held body  78  having an opening  80  covered by an apertured mesh  82 . Tool  76  comprises a motor  84  connected to a rotatable blade  86  by a drivetrain  88 . The apertured mesh  82  of tool  76  is pressed against margin  24  of tissue specimen  10  creating protruding damaged tissue  72  which is sliced off by the rotation of rotatable blade  86 . This creates a plurality of undamaged tissue regions  28 , shown in FIG. 12. Again, undamaged tissue may be collected, for example, from tool  76 , such as from blade  86 , or from undamaged tissue regions  28 .  
         [0063]    [0063]FIGS. 13, 14 and  14 A illustrate a sample collection assembly  90  comprising a generally tubular braided device  92  and a blade  64 . Tissue specimen  10  is placed into the interior of braided device  92  and the ends of device  92  are pulled to place device  92  into tension creating protruding damaged tissue  72  between the filaments or yarns  94  of device  92 . Protruding damaged tissue  72  is then removed using, for example, blade  68 .  
         [0064]    [0064]FIGS. 15, 16 and  17  and illustrates a sample collection assembly  96  comprising a specimen capturing and removal device  98  mounted to the distal end of a placement sheath  100 . This structure may be similar to that described in U.S. Pat. No. 6,221,006. Device  98  comprises an inner, tubular braided device  102  with apertures, similar to braided device  92  of FIG. 13, connected to an outer, tissue-impervious covering  104  along their joint distal edge  106 . Covering  104  is preferably a tubular braided device in which the apertures have been sealed so to prevent passage of tissue therethrough. A tissue specimen  10  is shown captured within device  98 . The provision of outer, tissue-impervious covering  104  helps to prevent seeding of tissue from specimen  10  when sample collection assembly  96  is used to capture and extract tissue specimen  10  from a patient. After the tissue specimen has been retrieved from the patient, the proximal end  108  of outer covering  104  is cut or otherwise separated from placement sheath  100  and pulled distally back over inner braided device  102  to place device  98  in tension thus squeezing tissue specimen  10  in much the same manner as shown in FIGS. 14 and 14A. Protruding damaged tissue  72  may then be removed from inner braided device  102  to provide access to undamaged tissue as discussed above.  
         [0065]    FIGS.  18 , and  19  illustrate a sample collection assembly  110  comprising a closed-end braided device  112 , within which a tissue specimen  10  is placed, and a generally cylindrical blade  114 . Blade  114  has a substantially continuous loop, curved blade edge  116  and a transverse dimension sized to provide a desired constricting force on braided device  112  and tissue specimen  10  therein as blade  114  is passed over braided device  12  severing protruding damaged tissue  72  as suggested in FIG. 19. FIG. 20 illustrates blade  114  being a coiled, generally cylindrical blade in which the transverse dimension of the blade can be adjusted according to the transverse dimension of the particular tissue specimen  10 . The resilience of blade  114  may be made such that it self-adjusts its diameter, over a range of diameters, according to the size of the tissue specimen.  
         [0066]    [0066]FIGS. 21 and 22 illustrate a sample collection assembly  118  comprising a cylindrical, open ended container  120  within which a tissue specimen  10  is inserted. Container  120  is preferably a cylindrical container but may have other cross-sectional shapes as well. The inside diameter of container  120  is preferably chosen to be somewhat smaller than the transverse dimension of tissue specimen  10  so that margin  24  of tissue specimen  10  conforms to the inner wall  122  of container  120  as suggested in FIG. 22. Assembly  118  also includes a cutting device  124  comprising a cylindrical blade  114  extending from a handle  126 . The diameter of blade  114  is chosen to be sufficiently less than the diameter of inner wall  122  so that when blade  114  is forced into container  120 , the gap between blade  114  and inner wall  122  is sufficient so that the layer of tissue removed from tissue specimen  10  has the desired thickness. Appropriate centering structure, such as an outer tube extending from handle  126  which engages the outer surface of container  120 , may be used. FIG. 23 illustrates tissue specimen  10  after removal of a portion of the damaged tissue layer from the margin of the tissue specimen to create a relatively large undamaged tissue region  28 . As discussed above, undamaged tissue for analysis may be obtained from, for example, the inner or outer surfaces of blade  114 , from the underside  32  of damaged tissue layer  26  (see FIG. 2), or from undamaged tissue region  28  of specimen  10 .  
         [0067]    FIGS.  24 - 26 A illustrate obtaining undamaged tissue from an excision void  128 , or other cavity, using a void wall tissue sample collection assembly  130 . Assembly  130  comprises an operational unit  132  from which an introducer sheath  134  extends. A radially expandable and contractible apertured void wall engagement device  136  is housed within introducer sheath  134  as the open distal end  138  of sheath  134  is passed along the tissue tract  140  and into excision void  128 . Engagement device  136  is then extended through open distal end  138  in a retracted state as shown in FIG. 25. Engagement device  136  is preferably a braided structure, truss structure or other structure that has apertures and that can be expanded to press against the void wall  142  of void  128  with sufficient force to cause void wall tissue to extend inwardly through the apertures in device  136 ; one example of this is shown in FIG. 26A with protruding damaged tissue  72  passing through generally circular apertures. Engagement device may be, for example, mechanically expandable, expandable using fluid pressure or expandable using electrical energy or heat. Assembly  130  also includes a radially expandable, rotatable blade  144  which passes along the inner surface  146  of device  136  when device  136  is in the expanded state of FIG. 26.  
         [0068]    [0068]FIG. 26A is an enlarged view of a portion of inner surface  146  of engagement device  136  illustrating the path  148  of blade  144  as it passes over surface  146  in the directional arrows  149  thereby severing protruding damaged tissue  72  and leaving behind undamaged tissue regions  28 . Blade  144  and device  136  can then be collapsed and withdrawn from excision void  128  and into introducer sheath  134  and introducer sheath may be removed from the patient. Tissue collected within engagement device  136  may be tested. All or only a portion of inner surface  146  may be acted on by blade  144 . Assembly  130  could be made with more than one blade  144 . Blade  144 , or other severing element, may not be a radially expandable element.  
         [0069]    It may be desirable to insert a balloon or other expandable element into excision void  128  after the removal of engagement device  136 , expand the expandable element against the newly exposed undamaged tissue regions  28 , collapse the expandable element, remove the expandable element from the patient, and reexpand the expandable element to provide access to undamaged tissue. The undamaged tissue may be analyzed using Touch Prep or other procedures. This procedure may also be used without first using assembly  130  when excision void  128  was made without significant damage to the tissue at void wall  142 .  
         [0070]    [0070]FIG. 27 illustrates a syringe-type tissue sampling device  150  comprising a needle  152  extending from a barrel  154  housing a plunger  156 . A stop  158  is used to control the insertion depth of  152  so that only undamaged tissue is removed for analysis.  
         [0071]    Similarly, a probe-like device could be placed to a certain depth inside the tissue sample and then the probe could sample certain characteristics of the tissue (including, but not limited to optical reflectivity/refractivity, impedance, resistivity, conductivity, etc.). This technology and method could then determine the characteristics and subsequent diagnosis of the ‘undamaged’ tissue. FIG. 28 illustrates two such probe-like devices, that is, tissue characteristic analysis devices  160  and  162 , device  160  having multiple tissue characteristic analysis probes  164  while device  162  has a single probe  164 . Two or more tissue characteristic analysis devices can be used together to measure impedance density or other characteristics that would indicate cancer, or some other condition, and potentially identify the depth of the item of concern. This is illustrated in FIG. 28 with device  162 A shown in dashed lines used in conjunction with device  162  for such measurements.  
         [0072]    Another aspect of the invention relates to the analysis of the removed tissue using imaging (or other diagnostic) techniques that would ignore tissue that has been damaged by the removal technologies used. The damaged tissue will have different characteristics than non-damaged tissue and these characteristics could be interpreted and programmed into imaging techniques so that the imaging techniques would ignore the tissues that generate these certain characteristics. Such imaging techniques include, but are not limited to MRI, US, PET, CT, X-ray, photo-spectral analysis, electron microscopic analysis, etc. One such device and method using the aforementioned imaging technologies (or other diagnostic modality) could be designed so that undesirable tissue characteristic(s) could be ignored.  
         [0073]    When orientation is not critical, one may place the entire sample into a container of, for example, saline, spin out all the liquid, and then evaluate the cells. This would result in a sampling of cells from all over the sample, not just particular places. This is very similar to the Pap technique that is used today. In the Pap “smear” technique, the tissue is swabbed. After that, the swab is rolled onto a slide for evaluation. Only about  10 % of the cells from the swab make it to the slide. The newer Pap technique is to place the swab in a bath of saline, remove the liquid from the cells, and then place the cells onto the slide. It is believed that this technique captures about 90% of the cells. This technique might also prove useful for tumorectomy procedures, as it would yield more cells, but would not give orientation. This technique may be accomplished in conjunction with an orientation method. This technique may also be used to see if there are any cancer cells on the surface of the tissue.  
         [0074]    Although the foregoing ideas have been described in some detail by way of illustration and example, for purposes of clarity of understanding, it will be obvious that certain changes and modifications may be practiced within the scope of the appended claims. For example, other techniques of tissue removal, such as reciprocating or vibrating mechanical cutting/severing devices or chemical etching procedures, could be used.  
         [0075]    Any and all patents, patent applications and printed publications referred to above are incorporated by reference.