Abstract:
Provided is a restorative breast implant device that can be used to replace lumpectomy tissue and prevent the late aesthetic deformities which may occur following lumpectomy or partial mastectomy. The disclosed implant is an inflatable device comprising an outer shell composed of a biological material and an inner chamber. The device may be inflated/filled with a biological filler material to conform the implant to a lumpectomy cavity&#39;s dimensions. In addition, the disclosed implant is able to attain a blood supply thereby insuring incorporation into the breast while resisting resorption. The restorative breast implant is also optionally radiolucent so as not to interfere with future surveillance imaging. Further, in contrast to synthetic radiopaque implants, the disclosed implant resists fibrosis and infection.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims benefit of U.S. Provisional Application No. 61/709,603, filed Oct. 4, 2012, and U.S. Provisional Application Ser. No. 61/716,658, filed Oct. 22, 2012, which are hereby incorporated herein by reference in their entirety. 
     
    
     FIELD 
       [0002]    The present application relates generally to devices, systems, and methods for using a restorative breast implant to replace breast lumpectomy (partial mastectomy) tissue. 
       BACKGROUND 
       [0003]    Lumpectomy of the breast for cancer is a surgical treatment technique to remove the portion of the breast affected by cancer with a zone of surrounding normal tissue thereby rendering it cancer free while preserving the reminder of the breast uninvolved with disease. When coupled with whole breast radiation therapy or radiation delivered locally, the survival rates for appropriately selected patients are equivalent to mastectomy. Selection of either lumpectomy or mastectomy for treatment of breast cancer is based on a number of variables. A lumpectomy to remove a tumor can drastically disfigure the breast. The potential breast deformity (size discrepancy) following lumpectomy is one of the principal determinants affecting the selection process. 
         [0004]    The volume of tissue removed during a lumpectomy ranges in size from about 2 cc to about 400 cc, more commonly from the size of a walnut (33 cc) to the size of a tangerine (85 cc), and leaves behind a cavity corresponding to that volume plus an additional deficit due to collateral atrophy from cautery use. Initially, the defect created fills with fluid in response to the injury. Over time, however, the fluid is reabsorbed resulting in a cavity that collapses due to a lack of structural support. This collapse is manifested topographically by distortion of the remaining breast architecture leading to a number of problems such as nipple deformity, breast deformity, and asymmetry with the opposite breast. This asymmetry can also cause problems with the proper fit of garments. 
         [0005]    The location of tissue removal and the pre-existing breast size are significant determinants of the aesthetic deformity that ensues. In most cases, radiation either through a whole breast (external beam) or a partial breast (local irradiation) approach further compounds the acquired deformity by inducing shrinkage, fibrosis, and contraction of the breast and lumpectomy cavity. Little can be done effectively to restore the normal breast contour once this process is completed. The resulting deformity can be considered permanent. 
         [0006]    Treatment options to correct the deformity can be performed immediately after the removal of the lumpectomy specimen in some cases (oncoplastic approach) if the following conditions are met: the breast is large enough; the surgeon has adequate training or a plastic surgeon is consulted with training in this area; the patient is willing to have additional breast scars and internal breast scarring from tissue rearrangement that may reduce effectiveness of future mammographic surveillance; and the patient is willing to undergo a balancing procedure on the opposite breasts with attendant scars and risk. Procedurally, the oncoplastic approach is impractical in most cases for these reasons and the general lack of training among breast oncologic surgeons as well as the difficulties of coordinating surgery with the plastic surgeon. 
       SUMMARY 
       [0007]    Provided is a restorative breast implant device that can be used to replace breast lumpectomy tissue that prevents the late aesthetic deformities which may occur following lumpectomy or partial mastectomy. Use of the device can greatly improve the aesthetics of the breast and for that reason increase the number of candidates for breast conserving surgery. 
         [0008]    The disclosed implant is an inflatable device (e.g., a balloon, pillow, or bag) comprising an outer shell composed of a biological material and an inner chamber. The device may be inflated/filled with a filler material to conform the implant to a lumpectomy cavity&#39;s dimensions. In addition, the disclosed implant may be vascularized thereby insuring incorporation into the breast while resisting resorption. The restorative breast implant is also optionally radiolucent so as not to interfere with future surveillance imaging. Further, in contrast to synthetic implants, the disclosed implant resists fibrosis and infection. 
         [0009]    The disclosed implant is optionally inflated/filled in situ after implantation. Therefore, the disclosed implant may be implanted percutanously. However, a pre-filled implant may also be implanted intraoperatively. 
         [0010]    The disclosed implant can be placed either immediately after the removal of the tissue or at some point post-operatively, e.g., after the removal of a partial breast radiotherapy balloon. Immediate to near immediate volume restoration can prevent subsequent collapse of the lumpectomy cavity following cavity fluid reabsorption and radiation induced fibrosis and shrinkage. 
         [0011]    These and other features and advantages of embodiments of the present disclosure will become more readily apparent to those skilled in the art after consideration of the following detailed description and accompanying drawings, which describe both the preferred and alternative implementations of the present disclosure. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0012]      FIGS. 1A and 1B  are perspective views of exemplary restorative post-lumpectomy implant devices attached to a tube ( FIG. 1A ) or catheter ( FIG. 2B ) and a syringe for in situ inflation. 
           [0013]      FIGS. 2A ,  2 B,  2 C, and  2 D are perspective ( FIG. 2A ), cross-sectional ( FIG. 2B and 2C ), and partially cut-away ( FIG. 2D ) views of an exemplary restorative post-lumpectomy implant device. 
           [0014]      FIG. 3  is a diagram illustrating an exemplary procedure for implanting a restorative post-lumpectomy implant device into the void created by a lumpectomy and optional regional radiotherapy followed by in situ inflation. 
           [0015]      FIG. 4  is a cross-section view of an exemplary percutaneous insertion device for implanting a restorative post-lumpectomy implant device 
       
    
    
     DETAILED DESCRIPTION 
       [0016]    The present disclosure now will be described more fully hereinafter. Indeed, these implementations can be embodied in many different forms and should not be construed as limited to the implementations set forth herein; rather, these implementations are provided so that this disclosure will satisfy applicable legal requirements. As used in the specification, and in the appended claims, the singular forms “a”, “an”, “the”, include plural referents unless the context clearly dictates otherwise. The term “comprising” and variations thereof as used herein is used synonymously with the term “including” and variations thereof and are open, non-limiting terms. 
         [0017]      FIGS. 1A and 1B  are perspective views of two exemplary embodiments of a restorative breast implant  100  fluidly attached by a valve  110  to either tubing  350  ( FIG. 1A ) or a catheter  300  ( FIG. 1B ) for use as an implant to fill a void created by a lumpectomy or partial mastectomy. Also shown in  FIGS. 1A and 1B  is a syringe  310  containing filler material  210  fluidly attached to the tubing  350  ( FIG. 1A ) or catheter  300  with a guide rod  320  engaged within the catheter  300  ( FIG. 1B ). These embodiments allow for in situ inflation of the restorative breast implant  100  after optional percutaneous delivery. 
         [0018]      FIG. 2A  is a perspective view of an exemplary restorative breast implant  100  containing a valve  110 . As shown in  FIGS. 2B-2C , the restorative breast implant  100  is an inflatable balloon/pillow composed of an outer shell wall  120  and an inner chamber  130  that can be inflated/filled with a filler material  210 .  FIGS. 2B and 2C  are cross-sectional views of the restorative breast implant  100  when fully inflated/filled ( FIG. 2B ) or partially inflated/filled ( FIG. 2C ) with a filler material  210 . Also shown in  FIG. 2B  is a cross-sectional view of an exemplary valve  110 .  FIG. 2D  is a partially cut-away view of the restorative breast implant  100  showing the outer shell wall  120  and filler material  210  within the inner chamber  130 . 
         [0019]    Referring again to  FIG. 2B , when fully inflated/filled, the restorative breast implant  100  can have a generally spherical shape with a volume of about 5 cm 3  to about 400 cm 3  (5 ml to 400 ml), including about 30 cm 3  to 400 cm 3  (30 ml to 400 ml), and 33 cm 3  to about 85 cm 3  (33 ml to 85 ml). Therefore, the restorative breast implant  100  can have a maximum volume of 30 ml to 400 ml, including 33 to 85 ml). However, other shapes and volumes are contemplated in order to conform the restorative breast implant  100  to a lumpectomy cavity&#39;s dimensions. The disclosed restorative breast implant  100  may be partially or fully inflated/filled with the filler material  210 . 
         [0020]    The outer shell wall  120  is composed of a pliable, optionally elastic, biomaterial that is non-immunoreactive and promotes vascularization. The outer shell wall  120  biomaterial can be a biological scaffold obtained from mammals or insects. Examples of biological scaffolds that can be obtained from mammals include decellularized dermis, mesothelium, or submucosa (e.g., urinary bladder, intestinal, or stomach). For example, the biomaterial may be acellular human dermis, such as ALLODERM Tissue Matrix (Life Cell, Branchburg, N.J.), MEDOR Matrix (Kensey Nash, Exton, Pa.), or DERMAMATRIX Acellular Dermis (Musculoskeletal Transplant Foundation®, DePuy SYnthes, West Chester, Pa.). The biomaterial may be mesothelium extracellular matrix, such as MESO BIOMATRIX (Kensey Nash, Exton, Pa.)). Alternatively, the biomaterial may be acellular non-human dermis, e.g., from a bovine or porcine animal, such as SURGIMEND, PRIMATRIX, DUREPAIR, XENFORM, or TISSUEMEND (TEI Biosciences, Boston, Mass.). A suitable biomaterial (e.g., mesh) may also be produced from a bioengineered silk, such as SERISCAFFOLD (Allergan Medical, Irvine Calif.). 
         [0021]    The filler material  210  is an injectable liquid or semi-solid biological material that is non-immunoreactive and promotes vascularization. For example, the filler material  210  may be a collagen, hyaluronic acid gel, lyophilized dermis, biological polymer, stroma, collagenous soft tissue lattice, adiopose tissue, silk, or a combination thereof. The filler material may be composed of particles (e.g., beads or granules) that arrange themselves in an ordering fashion to fill a space with the correct volume. The particles may be, for example, nanoparticles, microparticles, or combinations thereof. Therefore, in some embodiments, the particles have a mean diameter of about 1 nm to about 1 cm, including about 10 nm to about 10 μm, or about 100 nm to about 1 μm. The particles may be suspended in an injectable liquid or semi-solid material, such as a gel. The particles may be spherical or non-spherical. 
         [0022]    The filler material may contain cells, such as stem cells, progenitor cells, fat cells, or a combination thereof. The outer shell wall  120  biomaterial, the filler material  210 , or a combination thereof, optionally contains growth factors that promote angiogenesis and vascularization of the implant  100 . In some cases, the implant  100  releases vascular endothelial growth factor (VEGF). Therefore, in some cases, the filler material  210  contains cells containing recombinant expression vectors encoding one or more growth factors promote angiogenesis, such as VEGF. 
         [0023]    The outer shell wall  120  biomaterial and the filler material  210  can be derived from a homologous, autologous, or heterologous sources. In some cases, the outer shell wall  120  biomaterial and/or the filler material  210  is a xenograft derived from a non-human mammal, such as a bovine or porcine animal. However, the outer shell wall  120  biomaterial and/or the filler material  210  may also be an allograft derived from a human source or an autograft derived from the patient&#39;s own body. 
         [0024]    The outer shell wall  120  biomaterial and the filler material  210  are also optionally radiolucent so as not to interfere with future surveillance imaging. For example, the restorative breast implant  100  optionally has a radiodensity less than a silicone breast implant. 
         [0025]    The restorative breast implant  100  may be pre-filled at standard volumes for implantation without in situ inflation. This approach requires a larger incision for implantation, but avoids the need for a valve  110 . Therefore, restorative breast implants  100  are disclosed that lack a valve  110  and instead contain a fixed volume of filler material  210 . 
         [0026]    The valve  110 , when used, is a one-way or two-way valve that allows the physician to fill, and optionally empty, the restorative breast implant  100  with filler material  210 . For example, the valve  110  can be a leaf valve, a kink valve, or a diaphragm valve. The valve may be produced from a biocompatible synthetic material, such as silicone. Optionally, the valve is made from a biological material, such as those used to form the outer shell wall  120 . 
         [0027]    According to some embodiments, the restorative breast implant  100  is inflated/filled in situ with the filler material  210  after implantation within a cavity  500  created by a lumpectomy or partial mastectomy.  FIG. 3  is a diagram illustrating an exemplary procedure for implanting a restorative post-lumpectomy implant device. A deflated (unfilled or partially filled) restorative breast implant  100  is inserted through an incision  510  in the breast and guided to the lumpectomy cavity  500  using a catheter  300  and optional guide rod  320  attached to the restorative breast implant  100  by a valve  110  within the implant. The guide rod  320 , if used, is then retracted from within the catheter and discarded. A syringe is then attached to the catheter  300  and used to inflate the restorative breast implant  100  with a sufficient amount of filler material  210  to fill the lumpectomy cavity  500 . In other embodiments, a catheter and guide rod are not needed, so the deflated (unfilled or partially filled) restorative breast implant  100  is fluidly attached to the syringe  310  by tubing  350  connected to the valve  110 . 
         [0028]    A suitable volume of filler material  210  can be determined by visual inspection of the lump removed, the dimensions of the cavity being filled, by viewing the contour of the breast after correction with the implant, or any combination thereof. Once inflated, the catheter is detached from the valve  110  and removed from the breast. Optionally, the fill volume is subsequently adjusted to correct deformity. For example, a two-way valve may be used to permit adjustments up and down in volume as needed so long as the syringe is fluidly connected to the valve  110  on the implant. After the implant is placed and the volume optimized, the syringe  310  and catheter  300  is disconnected from the valve thereby sealing the valve and implant. The skin may then be closed over the implant, e.g., in two layers using interrupted and running inter-dermal sutures or two layers of running inter-dermal sutures. Wound sealant may also be placed, and antibiotics may be given prophylactically. 
         [0029]      FIG. 4  is a cross-section view of an exemplary percutaneous insertion device  600  for implanting a restorative breast implant  100 . The percutaneous insertion device  600  can be used to inflate/fill outer shell wall  120  biomaterial with the filler material  210  after percutaneous insertion. According to some embodiments, the percutaneous insertion device  600  comprises a dual-lumen tube having inner tube  620  and an outer tube  630 , wherein the inner tube  620  is sized and configured to slidably pass through the lumen of the outer tube  630 . The percutaneous insertion device  600  can also comprise a plunger  610  sized and configured to slidably pass through the lumen of the inner tube  620  so as to force filler material  210  through the inner tube  620  out its distal end. In preferred embodiments, the distal end of the inner tube  620  can extend beyond the distal end of the outer lumen  630  when the inner tube  620  is fully interposed within the outer tube  630 . In this conformation, the outer shell wall  120  can be secured to the outer surface of the inner tube  620  at its distal end by one or more elastics  650 . When the inner tube  620  is retracted in the proximal direction, the distal end of the outer tube  630  advances over the distal end of the inner tube  620  and displaces the one or more elastics  650  from the outer surface of the inner tube  620 . The percutaneous insertion device  600  can therefore be used to inflate/fill outer shell wall  120  biomaterial with the filler material  210  by first injecting the percutaneous insertion device  600  into a void created by a lumpectomy, advancing the plunger  610  to force filler material  210  through the inner tube  620  out its distal end into the outer shell wall  120  secured to the outer surface of the inner tube  620  at its distal end by one or more elastics  650 . Once the breast implant  100  is fully filled/inflated, the inner tube  620  is retracted to displace the one or more elastics  650  from the outer surface of the inner tube  620 , which creates a seal in the breast implant  100 . 
         [0030]    The disclosed restorative breast implant  100  may be implanted within a void created by a lumpectomy or partial mastectomy procedure any time after surgery, but is preferably implanted immediately or nearly immediately after a lumpectomy procedure or partial mastectomy. The term “immediate” as used herein refers to the same day as a medical procedure, i.e., while the patient is still in the operating room or doctor&#39;s office. The term “near immediate” includes a time period from 1 day to 2 weeks after a medical procedure. 
         [0031]    Also disclosed is a method for immediate to near immediate implant reconstruction following local/regional radiotherapy to the tumor bed using a catheter based implant device, such as MAMMOSITE (Hologic, Bedford, Mass.). For example, following removal of the MAMMOSITE device and cavity washout with antimicrobial solution (e.g., bacitracin/betadine), a deflated or partially inflated restorative breast implant  100  fluidly attached to the end of a deployable catheter  300  via a valve  110  may be inserted through the incision  510  used for the MAMMOSITE (approximately 2.5 cm) and placed into the lumpectomy cavity  500 . A deployable guide rod  320 , if used, is then retracted from within the catheter and discarded. A syringe  310  may then be attached to the catheter  300  and the filler material  210  injected into the implant  100 , filling it to the desired amount for optimal volume correction. Volume adjustments are possible until the fill catheter  300  and syringe  310  are removed. After the implant is placed and the volume optimized, the syringe  310  and catheter  300  are disconnected from the valve  110  thereby sealing the valve  110  and implant  100 . The skin may then be closed over the implant  100 , e.g., in two layers using interrupted and running inter-dermal sutures or two layers of running inter-dermal sutures. Wound sealant may also be placed, and antibiotics may be given prophylactically.