Abstract:
Apparatus and a method for depositing multiple implants carrying radioactive isotopes, pharmalogical agents or transgenes, in soft tissue including tumors and organs with precise, selectable spacing between implants includes an introducer in the form of a tube which is inserted into the soft tissue and an obturator for pushing implants out of the introducer one at a time. An operating mechanism incrementally withdraws the introducer while the obturator remains stationary thereby depositing a single implant. The obturator is then coupled to the introducer for the remainder of the stroke to provide the spacing. In a preferred embodiment, the introducer is resequenced to lay down parallel rows of implants. An indicator records the total number of implants deposited. The distal end of the introducer is configured to retain the implants and allow them to be discharged into the soft tissue singly. The invention is particularly suited, but not limited, to depositing the implants using laporascopic or thorascopic techniques.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to apparatus and a method for introducing implants such as radioactive seeds, or pellets or dissolvable capsules carrying medication or transgenes, into soft tissue such as tumors, and particularly intra-abdominal or intrathoracic tumors. Specifically, it relates to such an apparatus and method which deposits multiple implants in soft tissue with precise, selectable spacing between implants. 
     2. Background Information 
     It is known to inject radioactive seeds into the prostate to treat malignancies. Early devices for this purpose injected a single seed using a hollow needle from which the seed was ejected by a plunger. Later devices have the capability of introducing multiple seeds. Some deposit a single elongated implant having multiple seeds distributed longitudinally. Others have a plunger with multiple, axially spaced seed cavities inserted through a cannula with equally spaced side openings for laterally discharging the seeds. Neither of these approaches offer flexibility in the spacing between multiple implants. Furthermore, there is difficulty in laterally discharging the implants in the second arrangement. It has been proposed to incorporate small leaf springs in the cavities to push the implants clear of the cannula, but withdrawing the cannula past the seeds disturbs their positions and the diameter of the cannula must be enlarged to accommodate the springs. Still other multiple seed ejectors rely upon the user to set the spacing between seeds. The accuracy of this technique is dependent upon the skill of the user or requires fluoroscopy to monitor seed location. 
     There is a need for an improved apparatus for introducing implants into soft tissue. 
     There is a particular need for an improved apparatus for introducing multiple implants at precisely spaced locations within the soft tissue. 
     There is a related need for such apparatus with which the spacing between implants can be easily and accurately adjusted. 
     There is also a need for such apparatus which can be used to introduce implants into soft tissue within a cavity such as intra-abdominal and intrathoracic tumors. 
     There is an additional need for such apparatus which can be easily loaded and simple to use, and particularly which only requires one hand of the user to deposit the implants with precise spacing. 
     There is a further need for such a device which can be used for various types of implants, such as radioactive seeds, or pellets bearing or dissolvable capsules containing medications or transgenes. 
     SUMMARY OF THE INVENTION 
     These needs and others are satisfied by the invention which is directed to apparatus and a method for introducing implants into soft tissue at spaced intervals. 
     The apparatus includes an introducer in the form of an elongated tube having a distal end which is insertable into the soft tissue and within which a plurality of implants are retained. An obturator is slidable within the introducer from the proximal end. The apparatus further includes a sleeve through which the introducer slidably extends. An operating means incrementally withdraws the introducer rearward relative to the sleeve a distance L. Initially, the obturator remains stationary while the introducer is withdrawn so that an implant is pushed out of the end of the introducer. After the introducer has been withdrawn a distance L s  equal to the length of one implant, automatic coupling means of the operating mechanism couples the obturator to the introducer so that both the obturator and the introducer are withdrawn the remainder of the distance L. This distance L p  that the obturator and introducer are withdrawn together provides spacing between the implants. Thus, the implants are deposited within the soft tissue with precise spacing in between. In accordance with one aspect of the invention, this spacing L p  is adjustable. 
     The implants which are deposited by the apparatus of the invention can be radioactive seeds. They can also be dissolvable capsules containing medication or transgenes. The implants can also be resorbable pellets carrying medication or transgenes. The invention is particularly suitable for depositing implants in intra-abdominal and intrathoracic tumors. In such case, the sleeve of the apparatus can have a tubular extension which is inserted through an incision in the external wall defining the cavity in which the tumor is located. The tubular extension can be positioned for inserting the introducer into the tumor by a laparoscope or thoracoscope inserted through another small incision as is known. This eliminates the need to use a fluoroscope or an open incision to align the apparatus with a tumor. With the tubular extension on the sleeve properly aligned relative to the tumor, the introducer is extended through the tubular extension into the tumor. To this end, the introducer is provided with a sharpened end. 
     Several lines of spaced implants can be deposited within the tumor using the invention. After each line of implants has been deposited, the tubular extension is repositioned such as by using the laparoscope or thoracoscope and the procedure is repeated. As used throughout, the term “forward” will be used in reference to movement toward or into the soft tissue and the term “rearward” in reference to movement away from or out of the soft tissue. 
     The preferred embodiment of the invention is particularly suited for depositing multiple lines of implants in soft tissue. In this embodiment, the introducer has an enlarged proximal end in the form of a tubular member which is received in the sleeve. The means incrementally withdrawing the introducer comprises a trigger mechanism including a trigger supported on the tubular member. A slide is slidable forward relative to the tubular member upon actuation of the trigger. A one-way clutch locks the slide to the sleeve as the trigger is actuated so that, in effect, the slide remains stationary relative to the sleeve and the tubular member is incrementally withdrawn rearward the distance L with respect to the sleeve each time the trigger is actuated. The means automatically coupling the obturator to the introducer is a holding device engaged by the slide which holds the obturator stationary relative to the sleeve until the introducer has been withdrawn the distance L s . A slip clutch through which the obturator slips as the introducer moves the distance L s  couples the obturator to the introducer for movement with the introducer over the distance L p . 
     Preferably, the one-way clutch which locks the slide to the sleeve includes a rack and a pawl member, with the rack provided on the slide and the pawl member mounted on the sleeve. A spring biases the slide rearward upon release of the trigger. Means such as an O-ring resist forward movement of the tubular member relative to the sleeve in response to this bias. As the slide moves rearward, the pawl member slides over the rack teeth and the apparatus is ready for deposit of another implant by reactuation of the trigger. Each time the trigger is actuated, the tubular member, and therefore the introducer, moves incrementally rearward to deposit an implant and provide the spacing L p . When the desired number of implants have been deposited in a row, the pawl member is lifted, and the tubular member/introducer is slid forward relative to the sleeve to reset the introducer for laying down another row of implants. 
     In the preferred embodiment of the invention, the means holding the obturator stationary relative to the sleeve while the implant is deposited comprises a fore shuttle slidable in the tubular member, and a directional clutch blocking rearward movement of the obturator relative to the fore shuttle. This holding device further includes a decoupling spring between the slide and the fore shuttle holding the fore shuttle stationary relative to the sleeve while the introducer moves the distance L s  relative to the sleeve until the fore shuttle seats relative to the tubular member and is then carried rearward with the tubular member against the decoupling spring to provide the spacing L p  between implants. A return spring between the fore shuttle and the tubular member biases the fore shuttle away from seating relative to the tubular member and repositions it upon release of the trigger. The decoupling spring is stronger than the return spring so that initially the shuttle, and therefore the obturator, remains stationary relative to the slide, and the sleeve, while the introducer is withdrawn the distance L s . 
     In the above-described preferred embodiment of the apparatus, the means for adjusting the spacing L p  is in the form of a tubular adjusting member threaded onto the inner end of the tubular member forming an adjustable stop which limits the travel of the slide, preferably through engagement with the trigger. The preferred embodiment of the invention can be used without the sleeve. In such case, an implant is ejected from the introducer with each actuation of the trigger. The introducer must be manually retracted by the user to provide spacing between implants. 
     In another embodiment of the invention the means for incrementally withdrawing the introducer relative to the sleeve comprises a carriage slidable within the sleeve. It firer includes means reciprocating the carriage forward and rearward within the sleeve and means coupling the introducer to the carriage only as the carriage moves rearward. The means coupling the obturator to the introducer in this embodiment of the invention comprises a shuttle slidable in the housing and means positioning the shuttle for engagement by and movement rearward with the carriage after the introducer has been moved inward by the distance L s . The means positioning the shuttle for engagement by the carriage comprises a bias means such as a spring biasing the shuttle toward the carriage and a first stop against which the shuttle seats to set the distance L s  at which the shuttle is engaged by the carriage. 
     The means reciprocating the carriage within the sleeve in this second embodiment of the invention is a trigger assembly and a trigger coupling linking the trigger assembly to the carriage. The trigger assembly includes a trigger member mounted for rectilinear movement generally transverse to the introducer. The trigger coupling includes a coupling pin on either the trigger member or the carriage and a coupling slot in the other of the trigger member and the carriage oriented at an angle to both the rectilinear movement of the trigger member and the forward and rearward movement of the carriage and engaged by the coupling pin. A second bias means in the form of another spring biases the carriage forward. In this embodiment of the invention, the arrangement for adjusting the distance L p  between implants can be a device such as an adjustment screw setting the length L r  of the rectilinear movement of the trigger member. Alternatively, the same arrangement as described in connection with the preferred embodiment can be used to adjust the spacing L p  in this second embodiment. 
     In yet another embodiment of the invention, the means for repetitively, incrementally withdrawing the introducer relative to the sleeve is a walking mechanism which incrementally walks rearward in the sleeve the distance L. This walking mechanism comprises a first actuating member secured to the introducer adjacent the proximal end thereof. It further includes a glide slidable in the sleeve rearward of the introducer and a second actuating member secured to the glide. First and second clutch means restrain forward movement of the introducer and the glide respectively. A spring biases the introducer and glide apart. The first and second actuator members are positioned for movement toward each other in response to an external actuating force. As the second clutch means holds the glide against forward movement, the introducer is drawn rearward. The actuating members are separated by the spring upon release of the external force. As the first clutch means holds the introducer against forward movement, the glide is pushed rearward to complete the walking motion. In this embodiment, the means automatically coupling the obturator to the introducer is a shuttle slidable relative to the glide between the introducer and the glide. The shuttle is engaged by and moved rearward with the introducer after the introducer has moved rearward the distance L s . Means on the shuttle grip the obturator for rearward movement with the shuttle. The glide is provided with a shuttle stop limiting forward movement of the shuttle relative to the glide. A second spring biases the shuttle against the shuttle stop. A third clutch means restrains rearward movement of the obturator relative to the introducer. A fourth clutch means restrains rearward movement of the obturator with the introducer until the shuttle is engaged by the introducer. An adjustment means limits movement of the actuating members toward each other to adjust the spacing between implants. 
     As another aspect of the invention, restraining means are incorporated into the distal end of the introducer to prevent implants from falling out. This integral restraining means reduces the passage in the introducer at the distal end to an inscribed opening which is smaller in lateral dimension than that of the implants, yet is resiliently expandable for ejection of implants by the obturator. The restraining means comprises radially inwardly directed deformations and strain relief cuts in the introducer. The deformations may be in the form of a crimp or dimples. The cuts are either slits extending through the introducer wall or kerfs extending only partially through the wall. Preferably, these slits or kerfs are longitudinal, and they may be open ended, in that they extend to the distal end of the introducer, or they may be closed, stopping short of the distal end. 
     As a further aspect of the invention, a gauge provides an indication of the number of implants which have been deposited. This gauge is provided by a tubular housing mounted on the rear of the device into which the obturator extends. A graticule on a transparent tubular housing or a window in the housing provides a visual indication of the position of the obturator, and therefore, the number of implants deposited. Where adjustment of the spacing is provided by the tubular adjustment collar on the rearward end of the sleeve, and the tubular obturator housing is integral with this adjustment collar, a helical scribe line is provided on the obturator for cooperating for the graticule to maintain accuracy of the implant count with adjustment of the spacing L p . 
     A depth or penetration gauge can also be provided by a scale on a fully or partially transparent extension on the sleeve and a mark on the introducer which registers with the scale to indicate the depth of penetration of the introducer into soft tissue. 
     The invention also embraces a method of introducing a gene into soft tissue. This method includes loading an implant carrying a nucleic acid sequence encoding the gene into an introducer, inserting the introducer into the soft tissue, ejecting the implant into the soft tissue from the introducer, and withdrawing the introducer from the soft tissue. The soft tissue can be a tumor in which the gene can be used to suppress the growth of the tumor in serving as an anti-oncogene, anti-growth factor receptor, antisense message for binding of growth factor receptor, or other signal-transducing substances RNA or can stimulate apoptosis. Alternatively, the soft tissue could be an organ such as the liver or pancreas and the gene can provide for the direction of transcripts that reduce toxicity from cancer therapy such as adding antioxidant genes, radiation resistance gene product substances, or can add genes that produce transcripts for antisense endothelial cell or cell surface attachment molecules, thereby preventing metastasis of cancer cells from other sites into that organ such as the pancreas or liver. 
     The method includes depositing a plurality of implants in the soft tissue by loading them into the introducer and ejecting them from the introducer into the soft tissue one at a time in spaced relation. Preferably, the implants are deposited by inserting an obturator into the introducer behind the implants. The implants are injected by holding the obturator stationary relative to the soft tissue while the introducer is withdrawn. Multiple implants are ejected one at a time in spaced relation as the introducer is withdrawn from the soft tissue. Preferably this is accomplished by, repetitively withdrawing the introducer while holding the obturator stationary to eject an implant and then withdrawing the introducer and the obturator together to provide the spacing between implants. Multiple lines of implants can be deposited in this manner by reinserting the introducer into the soft tissue and laying down an additional line of implants. Where the soft tissue is located within the cavity such as the abdomen or the thorax, laporascopic or thorascopic techniques can be used to align the introducer for insertion into the soft tissue. Thus, the method includes inserting the introducer through an incision in an external wall defining a cavity containing the soft tissue and inserting an optical instrument such as a laparoscope or a thoracoscope into the cavity through another incision to visually align the introducer for depositing one or more rows of implants in the soft tissue. 
     While the implants are deposited in soft tissue in accordance with the invention by ejecting them from the distal end of the introducer through relative movement of the obturator toward the distal end of the introducer, the implant in fact remains in a fixed position in the soft tissue because the relative motion is produced by withdrawing the introducer while the obturator remains stationary thereby exposing the implant to the surrounding tissue. This provides several advantages. First, it minimizes trauma to the tissue. Second, it prevents an implant placed deeply in the tissue from being advanced beyond the distal margin of the tissue which would necessitate a tedious retrieval of the implant. Third, consistent separation of multiple implants within a single track and the location of the line of implants with respect to the surface of the soft tissue are assured. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     A full understanding of the invention can be gained from the following description of the preferred embodiments when read in conjunction with the accompanying drawings in which: 
     FIG. 1 is a schematic view illustrating use of the apparatus in accordance with the invention to deposit implants in a tumor such as an intrathoracic tumor with the aid of a thoracoscope to align the apparatus with the tumor. 
     FIG. 2 is an isometric view of an apparatus in accordance with the preferred embodiment of the invention as shown partially assembled. 
     FIGS. 3A and 3B together illustrate a longitudinal section through the apparatus of FIG. 2 shown assembled but in the unactuated initial state taken along the respective planes shown in FIG.  3 C. 
     FIG. 3C is an end view of the apparatus of FIG. 2 showing the planes of the sections of FIGS. 3A and 3B. 
     FIG. 4 is a partial view similar to FIG. 3A but showing the parts in the partially actuated condition where an implant has just been deposited. 
     FIG. 5 is a partial sectional view similar to FIG. 4 with the parts shown in the position in which the trigger has been fully depressed to provide the spacing between implants. 
     FIG. 6 is a partial sectional view similar to FIGS. 4 and 5 showing the position of the parts after the trigger has been released. 
     FIG. 7 is a longitudinal sectional view through apparatus in accordance with a second embodiment of the invention. 
     FIG. 8 is a longitudinal section through apparatus in accordance with a third embodiment of the invention. 
     FIGS. 9A-9C,  9 E and  9 F are isometric views of various embodiments of the distal end of the introducer which forms part of the apparatus of the invention. 
     FIG. 9D is an end view of the distal end of the introducer shown in FIG.  9 C. 
     FIG. 9G is a cross-section through the introducer of FIG.  9 F. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The invention is directed to an apparatus and method for depositing implants in soft tissue and particularly, but not necessarily, tumors. The term implant as used throughout refers to non-resorbable, permanent metal, or equivalent material containing a radioisotope, commonly referred to as radioactive seeds. It also refers to such materials used for brachytherapy. The term implant further includes capsules containing, or discrete carriers such as pellets coated with, vectors containing nucleic acid sequences encoding a gene of interest. The vectors can include viral and non-viral vectors. Appropriate vectors include but are not limited to adeno-associated virus vectors, adenovirus vectors, retroviral vectors, plasmids, lenti virus vectors, herpes virus vectors and any other form of viral or sub-cellular organism used as a vector for inserting transgenes. Such vectors could also include, for example, yeast artificial chromosome, human chromosome fragments, or sub-cellular components which can be used to introduce a gene of interest to soft tissue cells. Non-viral means for introducing nucleic acid sequences include but are not limited to liposomes, calcium phosphate, electroporation, and DEAE-dextran. Naked nucleic acid can also be introduced into the soft tissue including, for example, RNA, DNA, cDNA, oligonucleotides and anti-sense RNA. The implants can also contain or be coated with other therapeutic or prophylactic agents, such as a pharmaceutical or pharmacological material, a chemical or other molecular material which can be used to elicit a biological or physiological response. 
     The “gene of interest”, as that term is used herein, refers to any gene encoding a protein, peptide, or fragment thereof that the user desires to introduce to the soft tissue cells. Accordingly, the gene of interest will vary depending on the needs of the user, based upon such things as the illness or condition for which the gene is being introduced and the soft tissue being targeted. For example, the gene can encode a protein, peptide or fragment thereof that functions in a therapeutic or prophylactic manner in the soft tissue transduced by the gene. Examples include, but are not limited to, genes encoding for: an antisense molecule for any of the growth factors, such as any form of the transforming growth factors, fibroblast growth factors, or insulin-like growth factors; an antisense molecule for any growth factor receptor; an antisense molecule for any signal transduction molecule, such as a janus associate kinase (JAK) or STAT kinase; a growth inhibiting or apoptosis-inducing gene that would either limit cell growth or induce cell death; an apoptosis-inducing protein such as BAX (a non-dephosphorelatable form of BAD); a protein that inhibits a cell&#39;s antioxidant defenses, such as antisense for manganese superoxide dismutase, glutathione peroxidase, or any other naturally occurring anti-apoptotic protein or peptide; a protein, peptide or fragment thereof that limits vascularization; a protein, peptide or fragment thereof that prevents an angiogenic response, such as basic fibroblast growth factor (bFGF), human growth factor (HGF), or vascular endothelial growth factor (VEGF), by effecting endothelial cells within a tumor or inhibiting an angiogenic product; a cytokine, such as granulocyte macrophage colony stimulating factor (GM-CSF), any of the interleukins (IL), especially IL- 11 , IL- 7  and IL- 12 , the growth factors listed above, growth hormone, bone morphogenetic proteins, and any other cytokine or chemokine that elicits a response in cytotoxic T cells, NK cells, dendritic cells, macrophages, polymorphonucleoleukocytes, or other immune effector cells that lyse tumors; and toxins that kill tumor cells. 
     The implants can also contain or have coated thereon other materials or chemicals which would have a biological effect on the soft tissue. For example, the implants can comprise: cellular material; tissue culture medium and NK cells sensitized ex vivo to kill a tumor; other sensitized immune effector cells such as dendritic cells or cytotoxic T cells; chemotherapeutic drugs such as anthracycline antibiotics, antifolate, toxol or other agents or derivatives; and protective agents, such as superoxide dismutase, glutathione peroxidase, or cytokines known to induce protective effects within normal tissue, such as HGF, IL- 1  or GM-CSF, insertable into certain soft tissue, such as the liver or pancreas, to protect this tissue from the cytotoxic damage during radiotherapy to adjacent or associated organs. 
     It is also a feature of the present invention that the capsules be formulated with the appropriate resorbable material so as to effect a timed-release of the therapeutic or prophylactic agent in the soft tissue. In this manner, for example, drugs could be released slowly over time, providing a continuous exposure of these drugs to the effected soft tissue. The preparation of such capsules is within the skill of one practicing in the pharmaceutical arts. 
     The apparatus is particularly suitable for inserting an implant into specific sites in the abdomen or thorax where the introduction is carried out through a puncture wound and monitored by laparoscopic or thoracoscopic visualization of alignment of the device. It is also suitable for implanting radioiodine or radioactive palladium seeds in the prostate for prostate brachytherapy. In addition, it is suitable for use of female patients with carcinoma of the vulva, uteri, cervix, endometrium, or ovary with intravaginal introduction of radioisotope-containing implants or seeds. The apparatus is further suitable for treating tumor volumes reached by intrarectal, intraoral or intra-esophageal administration of the implants. It could be further used where the patient is a fetus within the uterine cavity and the implants are a resorbable material designed to implant transgenes for in utero gene therapy for the treatment or modification of inheritable diseases. 
     FIG. 1 illustrates application of the implanter apparatus  1  to depositing implants  3  in soft tissue located in a cavity defined by an external wall. In this case, the soft tissue  5  is a tumor located in the thorax  7  defined by the chest wall  9 . The apparatus  1  includes a sleeve  11  with a tubular extension  13  which is inserted through a trochar  15  inserted through a small incision  17  in the chest wall. A thoracoscope  19  is inserted through an adjacent small incision  21  so that the physician can align the implanter apparatus  1  with the tumor  5 . As will be described, the implanter apparatus includes an introducer  23  having a sharpened distal end  25  which penetrates the tumor. The introducer is inserted into the tumor to the depth at which the most distant implant is to be deposited. The introducer is then incrementally withdrawn to deposit a plurality of implants in a row. The length of the implants is L s  and the spacing between implants is L p . As will be described, the spacing L p  is easily adjustable. By repositioning the implant apparatus  1  using the thoracoscope  19 , additional rows of implants  3  can be deposited within the tumor  5 . It will be clear to those skilled in the art that laparoscopic techniques can similarly be used to deposit implants in intraabdominal soft tissue. Preferably, the tubular extension  13  is transparent and is provided with a depth graticule  13   g  which cooperates with a scribe lines  1  on the introducer to allow the surgeon to monitor the depth of penetration of the introducer  23 , and therefore the successive points of deposit of the implants  3 , in the tumor  5 . 
     The preferred embodiment of the implant apparatus  1  is illustrated in FIGS. 2,  3 A- 3 C,  4 - 6 . The apparatus  1  includes the sleeve  11  with its tubular extension  13  and a cartridge unit  27  which incorporates the introducer  23 . The cartridge unit  27  can be used by itself as will be described; however, preferably it is inserted into the sleeve  11  with the introducer  23  extending through the tubular extension  13  as indicated in the partially assembled view of FIG.  2 . 
     Referring particularly to FIGS. 3A and 3B, the cartridge unit  27  includes a tubular member  29  which forms an enlarged proximal end of the introducer  23 . For manufacturing purposes the tubular member is a separate part to which the introducer is attached by a hickey nut  33  which clamps a flange  31  on the introducer  23  against the tubular member  29 . This also allows the introducer to be a single-use item which may be provided already loaded with a supply of implants. The introducer  23  has a longitudinal passage  35  in which the implants  3  are retained. An obturator  37  is inserted into the passage  35  from the proximal end and bears against the implants  3 . The distal end  25  of the introducer  23  is configured in a manner to be described to retain the implants  3  in the passage  35 . 
     The apparatus  1  deposits the implants  3  by repetitively, incrementally withdrawing the introducer  23 . During the first part of this incremental withdrawing motion, the obturator is held stationary relative to the introducer. This results in the dropping off of an implant as illustrated in the lower part of FIG.  4 . During a second portion of the incremental withdrawal of the introducer  23 , the obturator  37  is coupled to and moves with the introducer over the distance L p . This distance L p  provides the spacing between implants. It can be appreciated that with successive incremental withdrawals of the introducer inward with the sleeve  11  over the distance L, a plurality of the implants  3  are deposited with a spacing L p  between implants. 
     This incremental withdrawal of the introducer and coupling and decoupling of the obturator to the introducer is effected by an operating mechanism  39 . This operating mechanism  39  includes an actuator  41  for incrementally withdrawing the introducer over the distance L and a coupler  43  for automatically coupling the obturator  37  to the introducer after the introducer has moved the length of a seed L s  and over the spacing distance L p . The actuator  41  includes a trigger  45 , a slide  47  slidable in the tubular member  29  and a one-way clutch  49  for selectively locking the slide  47  to the sleeve  11 . The trigger  45  is pivotally mounted by a pivot mount  51  inside the tubular member  29  and has a longitudinal groove  46  through which the obturator  37  extends. The trigger has a trigger cam surface  53  which engages an inclined slide cam surface  55 . As can be appreciated from FIGS. 3 and 4, actuation of the trigger results in movement of the slide  47  forward or to the right in FIG. 3 relative to the tubular member  29 . A pair of rearwardly extending wings  48  on the slide  47  straddle the trigger  45  to prevent the slide from rotating within the tubular member. 
     The one-way clutch  49  includes a rack  57  having a number of ratchet teeth  59  extending along the slide  47 . These ratchet teeth  59  have an engagement surface  61  facing forward. The one-way clutch  49  further includes a pawl member  63  pivotally mounted for rotation about a pivot  65  in a housing  67  on the sleeve  11 . A helical compression spring  69  biases teeth  71  on the pawl member  63  into engagement with the ratchet teeth  59  on the slide. Thus, it can be appreciated that when the trigger is actuated, with the slide held stationary relative to the sleeve  11  by the one-way clutch  49 , the tubular member  29  on which the trigger is mounted is withdrawn rearward relative to the sleeve  11 . As the introducer  23  is fixed to the tubular member  29 , it is also withdrawn rearward relative to the sleeve  11 . 
     The coupler  43  which automatically couples the obturator  37  to the introducer after the seed has been deposited, includes a holding device  73  formed by a shuttle  75  slidable within the tubular member  29  and a directional clutch  77  which allows the obturator to move forward relative to the shuttle but not rearward. A suitable directional clutch is a ball clutch which includes a number of ball bearings  79  which are jammed against the obturator  37  by a tubular ball race  81  by relative forward movement of the shuttle  75 . 
     The holding device  73  for the obturator  37  further includes a decoupling spring  83  between the slide  47  and the shuttle  75  and a shuttle return spring  85  between the shuttle and the forward end of the tubular member. The decoupling spring  83  and shuttle return spring  85  are helical compression springs with the decoupling spring being stronger than the shuttle return spring. The holding device  73  for the obturator also includes a slip clutch  87  which may take the form of an O-ring seated in the tubular member  29  and which bears against the obturator  37 . 
     The operation of the holding device  73  is as follows. When the trigger is actuated and the tubular member  29  moves rearward, the decoupling spring  83  holds the shuttle  75  stationary relative to the slide  47  and therefore also to the sleeve  11 . This results in compression of the shuttle return spring  85 . Thus, the introducer  23  is withdrawn while the obturator  37  is held stationary relative to the tumor by the directional clutch  77 . The resultant relative movement between the introducer and obturator deposits an implant  3  in the tumor. After the tubular member, and therefore the introducer, have been withdrawn the distance L s , the shuttle return spring  85  becomes fully compressed as shown in FIG.  4  and the shuttle  75  seats against and is carried with the tubular member/introducer  23  for the remainder of the distance L, or L p . As the shuttle  75  is withdrawn with the introducer  23 , the ball clutch  77  relaxes its hold on the obturator  37  but the slip clutch  87  pulls the obturator rearward with the tubular member, and therefore, the introducer the distance L p  as shown in FIG. 5 to set the spacing between implants. 
     Release of the trigger  45  allows the decoupling spring  83  and the shuttle return spring  85  to expand thereby applying a rearward force on the slide  47  and a forward reaction force on the tubular member  29 . This reaction force is resisted by an O-ring  89  in the sleeve  11  engaging the tubular member  29 . Therefore, the tubular member  29  remains stationary relative to the sleeve  11  and the slide  47  moves rearward with the pawl member  63  sliding over the rearward moving ratchet teeth  59  as shown in FIG.  6 . 
     In summary, each time the trigger  45  is actuated, the tubular member  29  and introducer  23  are withdrawn the distance L s  to deposit an implant  3 . The obturator  37  remains stationary until the implant is dropped and then moves with the introducer to provide the spacing L p  between implants. Upon release of the trigger  45 , the slide  47  moves rearward to position the parts for the next actuation. By repetitively actuating the trigger  45 , a row of implants  3  are deposited in the soft tissue  5  as described in connection with FIG.  1 . At the end of a row, a reset button  91  is depressed to disengage the pawl member  63  from the rack  57  so that the cartridge unit  27  can be reinserted fully within the sleeve  11  in preparation for depositing another row of seeds as shown in FIG.  3 A. 
     As pointed out, a feature of the apparatus in accordance with the invention is that the spacing L p  between the deposited implants  3  is readily adjustable. In the preferred embodiment of the invention, this adjustability is provided by an arrangement which limits the total distance L that the slide  47  can move within the tubular member  29 . With the distance L s  equal to the length of the implant remaining constant, this necessarily adjusts the spacing L p  between the implants. Preferably, the adjustment mechanism  93  is provided in the form of a tubular adjustment member  95  threaded onto the free end of the tubular member  29  as shown in FIG.  3 B. The forward end of the tubular adjustment member  95  has surface  97  which engages an adjustment cam surface  99  on the rear of the trigger  45 . Thus, the axial position of the tubular adjusting member  95  sets a limit on the stroke of the trigger which, in turn, through engagement of the trigger camming surface  53  with the slide cam surface  55 , limits the rearward movement of the slide and therefore the spacing L p . The tubular adjusting member  95  has a cylindrical cap  101  with a tapered skirt  103  which extends forward over the free end of the tubular member  29 . Indicia  105  on the skirt cooperate with a scribe line  107  on the tubular member to provide a quantitative measure of the spacing L p  as can be seen in FIG.  2 . Hence, the user can easily adjust the spacing L p  between implants by rotating the tubular adjusting member  95  to the desired setting. 
     The apparatus  1  also includes a housing  109  for protecting the obturator  37  which extends rearward out of the end of the tubular member  29 , and especially when the introducer  23  is fully loaded with implants. In the embodiment shown in FIGS. 2 and 3B, this housing  109  is formed integrally with the tubular adjustment member  95 . In order to provide an indication of the number of implants which have been deposited, the housing  109  can be made transparent (FIG. 3B) or be provided with a longitudinally extending window  110  (FIG.  2 ), which allows observation of the proximal end of the obturator  37 . A graticule  113  on the housing can then provide a numerical indication of the number of implants implanted by observing the position of the obturator  37  relative to the scale. Because the housing  109  is integral with the tubular adjustment member  29 , a helical scribe line  115  is provided adjacent the proximal end of the obturator to maintain the accuracy of the count of implants regardless of the spacing between implants selected. This helical scribe line  115  has the same pitch as the thread  117  on the tubular adjustment member  95 , but the pitch of the scribe line  115  has been exaggerated in FIG. 3B for clarity. 
     A second embodiment of the apparatus  201  is illustrated in FIG.  7 . In this embodiment, the operating mechanism  203  includes a carriage  205  slidable within the sleeve  207  and a trigger assembly  209  for reciprocating the carriage  205  forward and rearward within the sleeve  207 . The operating mechanism  203  further includes a trigger coupling  211  coupling the introducer  213  to the carriage  205  only as the carriage moves rearward. 
     The operating mechanism  203  of the implanter apparatus  201  also includes an aft shuttle  215  which is slidable within the sleeve  207  rearward of the carriage  205 . The aft shuttle  215  couples the obturator  217  to the introducer  213  after the introducer has moved the length of an implant L s . The aft shuttle  215  is positioned for engagement by rearward movement of the carriage  205  by a helical compression spring  219  which biases the aft shuttle forward against a stop formed by a snap ring  221 . 
     The trigger assembly  209  includes a trigger member  223 . The trigger member  223  is mounted in a slot  225  formed in the sleeve  207  for rectilinear movement generally transverse to the introducer  213 . The trigger member  223  includes a bifurcated center portion  227  which straddles the carriage  205 . The trigger coupling  211  includes a diagonal groove  229  in the body  227  of the trigger member, and a coupling pin  231  projecting laterally from the carriage  205  and engaging the diagonal groove  229 . A helical compression spring  233  biases the trigger member  223  upward as viewed in FIG.  7 . The trigger assembly  209  is actuated by pressing downward on the trigger member  223 . As the groove  229  is diagonal to both the rectilinear motion of the trigger member  225  and movement of the carriage  205 , the downward movement of the trigger member  223  results in rearward movement of the carriage  205 . Upon release of the trigger member  223 , the spring  233  biases the trigger member  223  upward and the carriage  205  forward. A one-way clutch in the form of the ball clutch  235  couples the introducer  213  to the carriage  205  only as the carriage moves rearward. As the carriage  205  moves forward, a slip clutch in the form of an O-ring  237  seated in the sleeve  207  overcomes the friction force tending to pull the introducer  213  forward along with the carriage  205 . 
     The carriage  205  has a collar  239  which engages the aft shuttle  215  after the carriage has moved rearward by the distance L s . When the collar  239  engages the aft shuttle  215 , the aft shuttle begins to move rearward and through the one-way ball clutch  241  pulls the obturator  217  rearward with it. Thus, the obturator  217  and introducer  213  move rearward together to provide the spacing L p  between implants. When the trigger member  223  is released, the carriage  205  is moved forward by the spring  233  which raises the trigger body  227  causing the coupling pin  231  on the carriage to be moved forward by translation of the diagonal coupling slot  229 . The spring  219  also moves the aft shuttle  215  forward against the stop  221  in preparation for the next actuation of the trigger member. As shown in FIG. 7, the spacing L p  between implants is made adjustable by adjusting the stroke L r  of the trigger member which determines the length of the overall withdrawal L of the introducer  213  with each trigger actuation. The stroke of the trigger L r  is made adjustable by a thumb screw  242  which limits downward travel of the trigger member. It will be appreciated, that alternatively the spacing L p  could be made adjustable by a tubular adjustment member on the end of the sleeve  207  similar to that described in connection with the embodiment shown in FIG. 2. A slip clutch formed by the O-ring  243  seated in an end cover  245  on the sleeve  207  prevents forward movement of the obturator  217  as the aft shuttle  215  is repositioned forward upon release of the trigger mechanism. It will be further appreciated that the apparatus  201  of FIG. 7 can also have an indicator of the number of implants deposited similar to that shown in the embodiment of FIG.  2 . Because the adjustment of the spacing L p  is provided by the thumb screw  242 , the housing for the obturator does not move with the adjustment, and therefore an annular rather than a helical scribe line is all that is needed on the obturator. In fact, the end of the obturator can be read against the graticule to determine the number of implants deposited. 
     A third embodiment of an implanter apparatus  301  in accordance with the invention is illustrated in FIG.  8 . In this embodiment, the introducer  303  is incrementally withdrawn rearward within the sleeve  305  by an operating mechanism  307  in the form of a walking mechanism  309  which walks the introducer  303  rearward in repetitive, small steps equal to the distance L. The walking mechanism  309  includes a first actuating member  311  having a body section  313  secured to the proximal end of the introducer  303  and slidable within the sleeve  305 . The first actuating member  311  also has an elongated grip  315  which extends outward through a longitudinal slot  317  in the sleeve  305  and then rearward where it terminates in a finger hole  319 . 
     The walking mechanism  309  of the implanter  301  also includes a glide  321  slidable within the sleeve  305  rearward of the first actuator body  313 . A second actuating member  323  connected to the glide  321  projects outward through the slot  317  and is aligned with the finger hole  319  of the first actuating member  311 . A first one-way clutch in the form of ball clutch  325  blocks forward movement of the first actuating member  311 , and therefore the introducer  303 , which is fixed to it. A second one-way clutch in the form of ball clutch  327  prevents forward movement of the glide  321 , and therefore the second actuating member  323 . 
     The operating mechanism  307  also includes a coupling device  329  for automatically coupling the obturator  331  to the introducer  303  after the distance L s . This coupling device  329  includes a shuttle  333  which is captured by, but slidable relative to, the glide  321 . As shown in FIG. 8, the shuttle  333  has a flange  335  on the rearward end which is engaged by a radial inward lip  337  on the glide which forms a forward stop for the shuttle relative to the glide. A helical compression spring  339  biases the shuttle  333  forward against the stop formed by the radial lip  337 . A second, stronger helical compression spring  341  biases the first actuator body  313  and the glide  321  apart. A third clutch, preferably in the form of the ball clutch  343  provided on the body  311  of the first actuating member, restricts inward movement of the obturator  321  relative to the introducer  303 . A fourth clutch  345  mounted in the shuttle  333  couples the obturator  321  to the shuttle  333 . 
     The operation of the implanter apparatus  301  is as follows. With the parts in the unactuated position as shown in FIG. 8, the user squeezes the finger hold  319  of the first actuating member and the second actuating member  323 . This produces equal and opposite forces F 1  in the forward direction on the second actuating member  323  and F 2  in the rearward direction on the first actuating member  311  through the finger hold  319 . As the ball clutch  327  prevents forward movement of the glide  321  and therefore the second actuating member  323  in response to the force F 1 , the first actuating member  311  and therefore the introducer  303  are drawn rearward. The obturator  321  is held stationary by the clutch  345  and the spring  339 . When the introducer  303  has been withdrawn the length of an implant L s  the aft shuttle  333  is contacted and begins to move rearward compressing the spring  339 . The clutch  345  couples the obturator  321  to the shuttle  333  so that the introducer  303  and obturator  321  move rearward together through the distance L p . 
     When the user relaxes the forces applied to the actuating members, the spring  341  applies a force tending to push the first actuating member  311  forward and the glide  321  and second actuating member  323  rearward. As the clutch  325  prevents forward movement of the first actuating member  311  and therefore the introducer  303 , the glide  321  is moved rearward. The shuttle  333  is held against the first actuating member body  313  by the spring  339  until the flange  335  on the shuttle is engaged by the radial lip  337  on the glide, and the shuttle is pulled rearward with the glide. The obturator is not dragged rearward with the glide  321  because the clutch  343  overpowers the clutch  345  and holds the obturator  321  stationary relative to the introducer  303 . 
     Adjustment of the spacing L p  between implants is provided by an adjustment screw  347  which limits movement of the first actuating member  311  and the second actuating member  323  toward each other. 
     Another aspect of the invention is the configuration of the distal end  25  of the introducer  23 . Examples of various configurations of the distal end  25  of the introducer  23  possible in accordance with the invention are shown in FIGS. 9A-9G. The distal end  25  performs two functions: 1) penetration of the soft tissue, and 2) containment of the implants for controlled discharge. The first function is accomplished by sharpening the distal end  25  such as by a single  347  or double  349  chamfer. Containment of the implants is implemented by an integral restraining mechanism  351  incorporated into the distal end  25  which reduces the passage  35  to an inscribed circular opening which is smaller in lateral dimension than the implants  3 , yet is resiliently expandable for ejection of implants by the obturator  37 . The restraining mechanism  351  includes radially inwardly directed deformations  353  in the wall  355  of the tube forming the introducer  23  and strain relief cuts  357  in the introducer tube. The deformations  353  may be a crimp  353   c  in the tube or dimples  353   d . The cuts are either slits  357   s  extending through the introducer wall  355  or kerfs  357   k  extending only partially through the wall. Preferably, these slits  357   s  or kerfs  357   k  are longitudinal, and they may be open ended, in that they extend to the distal end of the introducer, or they are closed, stopping short of the distal end. In the example shown in FIG. 9A, two diametrically opposite open slits  357   s  extend longitudinally through the tube wall  355 . One half  25   a  of the split end is chamfered at  347  and the other  25   b  maintains a square end but is tapered downward to a thin edge. The two halves  25   a  and  25   b  are crimped at  353   c . In the configuration of FIG. 9 b , a single open longitudinal slit  357   s  extends from the innermost point of a single chamfer  347 . A single open kerf  357   k  is located diametrically opposite the slit  357   s  and the distal end  25  is crimped at  353   c.    
     A pair of diametrically opposite open longitudinal slits  357   s  are centered on a single chamfer  347  on the distal end  25  of the introducer  23  shown in FIG.  9 C. FIG. 9D illustrates a preferred manner of forming the crimp as applied to the embodiment of FIG.  9 C. The triangle crimp  353   t  produces an inscribed circle  363  having a diameter d 1  which is less than the diameter d 2  of the passage  35  in the tubular introducer. However, the strain relief slits  357   s  allow the sharpened distal end  25  to expand and eject an implant pushed forward by movement of the obturator relative to the introducer. In the embodiment of FIG. 9E, a double chamfer  349  produces a pair of pointed ends  359 . A single open longitudinal slot  357  extends from a root between the two pointed ends  359  which are crimped at  353   c.    
     FIGS. 9F and 9G illustrate another embodiment of the restraining mechanism  351  incorporated into the sharpened distal end  25  of the introducer. Here, the deformations take the form of three circumferentially spaced dimples  353   d , and the strain relief cuts are three equally spaced closed, longitudinal slits  357   s . As shown in FIG. 9G, the dimples  353   d  reduce the passage  35  to an inscribed circle  363  having a diameter smaller than the diameter of an implant. Again, the slits  357   sc  allow the distal end  25  to resiliently expand for ejection of implants. 
     Preferably, as previously discussed, the introducer  23  is a disposable component which comes packaged with a supply of implants  3  contained in the passage  35 . The replacement introducer is secured to the tubular member  29  by the hickey nut  33  in the embodiment of FIGS. 2-6. 
     While specific embodiments of the invention have been described in detail, it will be appreciated by those skilled in the art that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure. Accordingly, the particular arrangements disclosed are meant to be illustrative only and not limiting as to the scope of invention which is to be given the full breadth of the claims appended and any and all equivalents thereof.