Abstract:
The present invention relates to circular anastomosis stapler kits that deliver a therapeutic agent followed by stapling of tissue. Each device has a stapling head with a shaft extending from said stapling head and a removable anvil and an interchangeable delivery head for delivering a therapeutic agent into the tissue. The present invention also relates to methods for using the kits and devices therein.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to surgical instruments and methods for enhancing properties of tissue repaired or joined by surgical staples and, more particularly to surgical instruments and methods designed to apply a therapeutic material to enhance the properties of repaired or adjoined tissue at a target surgical site, especially when sealing an anastomosis between adjacent intestinal sections. 
       BACKGROUND OF THE INVENTION 
       [0002]    Throughout the years the medical field has utilized various techniques in an effort to join or bond body tissue together. Historically, suturing was the accepted technique for rejoining severed tissues and closing wounds. Suturing was historically achieved with a surgical needle and a suturing thread, and more recently, with a variety of polymeric or metallic staples. The intended function of sutures is to hold the edges of a wound or tissue against one another during the healing process so as to reduce discomfort, pain, scarring and the time required for healing. Staples have recently been used to replace suturing when joining or anastomosing various body structures, such as, for example, the bowel. The surgical stapling devices employed to apply these staples are generally designed to simultaneously cut and seal an extended segment of tissue in a patient. 
         [0003]    Linear or annular surgical stapling devices are employed by surgeons to sequentially or simultaneously apply one or more rows of surgical fasteners, e.g., staples or two-part fasteners, to body tissue for the purpose of joining segments of body tissue together and/or for the creation of an anastomosis. Linear surgical stapling devices generally include a pair of jaws or finger-like structures between which body tissue to be joined is placed. When the surgical stapling device is actuated and/or “fired,” firing bars move longitudinally and contact staple drive members in one of the jaws, and surgical staples are pushed through the body tissue and into and against an anvil in the opposite jaw thereby crimping the staples closed. A knife blade may be provided to cut between the rows/lines of staples. 
         [0004]    Annular surgical stapling devices generally include an annular staple cartridge assembly including a plurality of annular rows of staples (typically two or three), an anvil assembly operatively associated with the annular cartridge assembly, and an annular blade disposed internal of the rows of staples. In general, an end-to-end anastomosis stapler typically places an array or group of staples into the approximated sections of a patient&#39;s bowels or other tubular organs. The resulting anastomosis contains an inverted section of bowel which contains numerous “B” shaped staples to maintain a secure connection between the approximated sections of bowel. 
         [0005]    Anastomotic leaks may result in significant morbidity and frequently death. In addition to the use of surgical staples, sealants, e.g., synthetic or biological sealants, can be applied to the surgical site to guard against leakage. The biological sealants are typically applied to the outer surface of the anastomosis using a dual lumen syringe or spray nozzle in a separate step. The delivery of the sealant can be compromised by an inability to get at or between individual staple sites, and along staple lines and tissue seams. 
         [0006]    U.S. Patent Application No. 2013/0068819 entitled “Structure Containing Wound Treatment Material”, discloses an anvil assembly for a circular stapling apparatus, where the anvil assembly includes an anvil head configured to support an anvil plate thereon; a shaft extending from the anvil head and configured to selectively engage a connection member of the circular stapling apparatus; an anvil plate operatively connected to the anvil head, the anvil plate defining a plurality of staple forming pockets therein; and a wound treatment material disposed in each staple forming pocket of the anvil plate. The wound treatment material is at least one of an adhesive, a sealant, a hemostat and a medicament. 
         [0007]    U.S. Patent Applications Nos. 2011/0147432 and 2006/0108393, both entitled “Structure for applying sprayable wound treatment material”, relate to surgical instruments, structures and methods for enhancing the properties of tissue to be repaired or joined and disclose a surgical stapling apparatus including a wound treatment material dispersion system for delivering wound treatment material to a target surgical site. The dispersion system includes an aperture formed in the anvil assembly oriented to dispense wound treatment material in an outward direction; and a source of wound treatment material in fluid communication with the aperture of the anvil assembly. 
         [0008]    U.S. Patent Application No. 2011/0014181 entitled “Microneedle Delivery Device and Methods of Using Same” describes microneedle bioactive agent delivery systems, associated apparatus and methods of using such. The microneedles described are deliverable using a needle or syringe apparatus that can interface with existing medical devices or the devices can be used as standalone systems. The systems deliver at least one bioactive agent to a tissue in need thereof, for example, the myocardium. 
         [0009]    U.S. Patent Application No. 2007/0038181 entitled “Method, system and device for delivering a substance to tissue” discloses devices and methods for delivering a substance to tissue or organs, particularly, the bladder, by a plurality of microneedles. The devices may include a delivery tube, a substance chamber to fill with the substance to be delivered, a plurality of needles, a plunger coupled to a handle movable relative to the tube to deliver the substance to the tissue through the needles, and a protective plate having at least one orifice therein, such that when the device is in a first, resting, position the needle tips are on a first side of the protective plate, and when the device is in a second, operational, position, the needles are on a second side of the protective plate. 
         [0010]    U.S. Pat. No. 8,281,975, entitled “Surgical apparatus and structure for applying sprayable wound treatment material” discloses an apparatus for forming an anastomosis between adjacent sections of tissue. The apparatus includes a body portion; an actuation assembly operatively supported at a proximal end of the body portion; an anvil assembly movably mounted at the distal end of the body portion for movement toward and away from the body portion; an approximation assembly extending between the body portion and the anvil assembly for moving the anvil toward and away from the tubular body portion; a dispersion assembly operatively associated with the approximation assembly, the dispersion assembly including at least one angled surface defining at least one channel interposed between the anvil assembly and the body portion and being configured to dispense a fluid therefrom; and at least one conduit for conducting wound treatment material to the dispersion assembly. 
         [0011]    U.S. Pat. No. 8,152,042 entitled “Annular Adhesive Structure” discloses an apparatus for sealing at the anastomotic site. In some embodiments, a washer or structural body is wrapped completely around an anvil shaft, with staples driven through the structural body to release the sealant. 
         [0012]    U.S. Pat. No. 7,972,357 entitled “Extraluminal sealant applicator and method” and U.S. Pat. No. 7,744,624 disclose apparatus for applying sealant to a target tissue of a surgical site. The apparatus includes a handle, a conduit and an end effector. The handle has means configured and adapted for operating the end effector and dispensing biological sealant to the surgical site via the end effector. The conduit stores and/or carries sealant towards the end effector. The end effector is configured to clamp around a body organ or tissue and apply and confine biological sealant in a substantially uniform manner. More specifically, the references disclose a system for applying sealant to a target tissue of a surgical site, comprising: a two-part sealant comprising a first part and a second part; an apparatus comprising: a handle; an end effector in operative association with the handle, the end effector including a first jaw member, a second jaw member, and a sealant-applying structure configured for applying sealant to the target tissue; the first jaw member being in fluid communication with a first conduit and a second conduit to convey sealant to the sealant-applying structure; the second jaw member being in fluid communication with a third conduit and a fourth conduit to convey sealant to the sealant-applying structure; the first and third conduits configured for conveying the first part of the two-part sealant to the sealant-applying structure; and the second and fourth conduits configured for conveying the second part of the two-part sealant to the sealant-applying structure. 
         [0013]    U.S. Pat. No. 8,096,458 entitled “Pouch used to deliver medication when ruptured” describes a surgical stapling device, comprising: a handle portion; an elongate body portion; and a head portion located at the distal end of the body portion, the head portion including an anvil assembly, a staple cartridge assembly and a knife blade, the staple cartridge assembly having an annular array or group of staples, the anvil assembly being connected to the body portion along a shaft, the anvil assembly including: an anvil plate defining a plurality of staple forming pockets therein and a recess; and a wound treatment material disposed substantially within the recess. 
         [0014]    U.S. Pat. No. 8,241,308 entitled “Tissue fastening devices and processes that promote tissue adhesion” discloses a fastener for fastening tissue segments having tissue surfaces, the fastener comprising: a first fastener member defining a fluid opening configured to receive a therapeutic agent, a plurality of fluid ports configured to deliver the therapeutic agent to the tissue segments, and a passageway between the fluid opening and the plurality of fluid ports; and a second fastener member having a substantially flat base and a post extending from the base proximate a center of the base, the post defining an opening for receiving and retaining the first fastener member such that the tissue segments to be fastened are retained between the first and second fastening members, the substantially flat base extending radially beyond a periphery of the post; wherein a longitudinal axis extends through the fluid opening, the fluid ports being radially arranged about the axis. 
         [0015]    Post-operative leakage of the anastomotic seals has been shown to lead to morbidity and mortality. A number of technologies are related to direct application of material to the serosal layer after stapling by either dripping or spraying. The problems associated with this technique are that access is very difficult and it is challenging to assess whether or not the material was applied to the right spot and completely around the anastomosis. The material is also applied on top of the serosal layer when the target site is actually subserosal along the staple line. Applying a therapeutic agent to the serosal layer of the colon requires the material to migrate through the serosa and to the staple region, then provide a biological affect, and overcome the problems associated with a leak formation, all within 24-48 hours, assuming the material was applied to the correct spot intraoperatively. One of the most challenging steps in the application of a topical adjunctive therapy to a colorectal anastomosis is to provide the material to the site because of the extreme limitation in access to the site. Some colorectal anastomoses are performed relatively “low” in a patient (i.e. lower anterior resection) and the actual staple line is deep within the pelvic canal, which makes a topical application of material around the circumference very difficult. Other technologies attempt to deliver the materials upon deploying of the stapler, resulting in complex equipment which delivers materials into highly compressed tissue. 
       SUMMARY OF THE INVENTION 
       [0016]    The present invention relates to surgical instruments and methods for enhancing properties of tissue repaired or joined by surgical staples and, more particularly to surgical instruments and methods designed to apply a therapeutic material to enhance the properties of repaired or adjoined tissue at a target surgical site, especially when sealing an anastomosis between adjacent intestinal sections so as to improve tissue viability and to prevent leakage. 
         [0017]    The present invention, in one embodiment, relates to a circular anastomosis stapler kit that delivers a therapeutic agent followed by stapling of tissue. The kit contains a device having a stapling head with an extending shaft and an anvil. The anvil can be removably connected to the shaft and a delivery head for delivering a therapeutic agent into the tissue. The delivery head has a cylindrical-shaped body with a front side and an opposing rear side, a central cylindrical opening therethrough that slidably moves over the shaft, a channel within the ring-shaped body terminating in a port opening on the front side and a plurality of circumferentially positioned hollow microneedles disposed on the front side surface of the ring-shaped body that are in fluid communication with the channel. The port opening can be connected to a pressurized therapeutic agent delivery system, wherein the pressurized therapeutic agent delivery system can include a syringe. The delivery head can have at least 10 hollow microneedles that are from 50 microns to about 1000 microns in diameter and from about 100 microns to about 2000 microns long. The delivery head can further include a plurality of circumferentially positioned hollow microneedles that are disposed on the rear side and in fluid communication with the channel. The front side of the delivery head can face a proximal lumen of the tissue, while the rear side would face a distal lumen of the tissue. The delivery head can be composed of two half-ring hollow bodies that are joined together by a joining means, such as a hinge, a plurality of pins or a plurality of magnetic strips. The therapeutic agent can be a drug, an enzyme, a growth factor, a peptide, a protein, a nutrient, an excipient, a cell, or combinations thereof. 
         [0018]    The present invention, in another embodiment, relates to method for performing anastomosis by sliding the delivery head described above onto the shaft, bringing the microneedles in contract with the tissue, delivering the therapeutic agent into the tissue through the microneedles, removing the delivery head from the shaft, and stapling the tissue. The time elapsed after the step of delivering the therapeutic agent into the tissue until starting the step of stapling the tissue is preferably at least 20 seconds. The therapeutic agent is preferably injected into a non-compressed tissue. 
         [0019]    The present invention, in another embodiment, relates to a method for performing anastomosis by positioning a stapling head of a stapler in a proximal tissue lumen and positioning an anvil of the stapler in a distal tissue lumen; slidably positioning a first delivery head on a shaft extending from the stapling head with a front side of the first delivery head facing the proximal tissue lumen and slidably positioning a second delivery head on a shaft or anvil pin connected to an anvil with a front side of the second delivery head facing the distal tissue lumen; sliding the first delivery head towards the stapling head, until the microneedles pierce the proximal tissue lumen; expressing a therapeutic agent from a first syringe connected to the port on the first delivery head causing the therapeutic agent flow through the channel and through the microneedle channels into tissue of the proximal tissue lumen; concurrently or sequentially with the two preceding steps, sliding the second delivery head towards the anvil until the microneedles pierce the distal tissue lumen; expressing the therapeutic agent from a second syringe connected to the port on the second delivery head causing the therapeutic agent flow through the channel and through the microneedle channels into tissue of the distal tissue lumen; removing the delivery head from the shaft; and connecting the stapler head to the anvil and performing stapling of the proximal and the distal tissue lumen with the stapler. The delivery head comprises a ring-shaped body having a centering cylindrical opening and at least one channel through the body that terminates in a port opening; a plurality of circumferentially positioned hollow microneedles disposed on the front side having microneedle channels in fluid communication with the channel. The delivery head preferably has at least 10 hollow microneedles that are from 50 microns to about 1000 microns in diameter and from about 100 microns to about 2000 microns long. The therapeutic agent is preferably a drug, an enzyme, a growth factor, a peptide, a protein, a nutrient, an excipient, a cell, or combinations thereof. 
         [0020]    The present invention, in another embodiment, relates to a method for performing anastomosis by positioning a stapling head of a stapler in a proximal tissue lumen and positioning an anvil of the stapler in a distal tissue lumen; slidably positioning a delivery head comprising a ring-shaped body having a centering cylindrical opening on a shaft extending from the stapling head and connected to the anvil; approximating the stapling head and the anvil until the microneedles pierce the proximal and the distal tissue lumen; expressing a therapeutic agent from a syringe connected to the port causing the therapeutic agent flow through the channel and through the microneedle channels into tissue of the proximal and the distal tissue lumens; removing the delivery head from the shaft; and stapling the proximal and the distal tissue lumen with the stapler. The delivery head has a channel within the body terminating in a port opening, a plurality of circumferentially positioned hollow microneedles that are disposed on a front side of the delivery head facing the stapling head and on an opposing rear side of the delivery head facing the anvil that are in fluid communication with the channel. The delivery head preferably has at least 10 hollow microneedles that are from 50 microns to about 1000 microns in diameter and from about 100 microns to about 2000 microns long. The delivery head can be composed of two half-ring hollow bodies that are joined together by a joining means, such as a hinge, a plurality of pins, or a plurality of magnetic strips. The therapeutic agent can be a drug, an enzyme, a growth factor, a peptide, a protein, a nutrient, an excipient, a cell, or combinations thereof. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0021]      FIGS. 1A ,  1 B and  1 C show prospective view and schematic cross-sectional views of a surgical anastomosis stapling instrument or stapling device for performing a circular anastomosis stapling operation. 
           [0022]      FIGS. 2A and 2B  show schematic cross-sectional side views of anastomotic joints of tubular lumens. 
           [0023]      FIGS. 2C ,  2 D,  2 E,  2 F and  2 G show additional cross-sectional frontal views of anastomotic joints. 
           [0024]      FIG. 3  shows schematic prospective view of an embodiment of the delivery head of the present invention. 
           [0025]      FIGS. 4A and 4B  show schematic cross-sectional views of embodiments of the delivery head of the present invention. 
           [0026]      FIGS. 5A and 5B  show schematic longitudinal cross-sectional views of embodiments of the delivery head of the present invention. 
           [0027]      FIG. 5C  shows an additional frontal view of an embodiment of the present invention. 
           [0028]      FIGS. 6A ,  6 B,  6 C,  6 D,  6 E and  6 F show schematic longitudinal cross-sectional views of embodiments of the present invention in operation during anastomosis using the anastomotic stapler. 
           [0029]      FIGS. 7A ,  7 B and  7 C show schematic cross-sectional side views of embodiments of the delivery head of the present invention. 
           [0030]      FIG. 8  shows schematic prospective view of an embodiment of the delivery head of the present invention. 
           [0031]      FIGS. 9A and 9B  show schematic cross-sectional side views of embodiments of the present invention in operation during anastomosis using the anastomotic stapler. 
           [0032]      FIGS. 10A ,  10 B,  10 C,  10 D,  10 E,  10 F, and  10 G show schematic cross-sectional side views and prospective views of alternative embodiments of the present invention and the embodiments in operation during anastomosis using the anastomotic stapler. 
           [0033]      FIGS. 11A ,  11 B, and  11 C show schematic prospective views of alternative embodiments of the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0034]    Colorectal surgery often involves the resection of a segment of the colon and rectum. Following a colorectal resection, the colon and rectum are drawn together with a circular stapler or handsewn, and an end-to-end anastomosis is performed. Post-op leakage of the anastomosis has been shown to lead to morbidity and mortality. 
         [0035]    Referring now to  FIG. 1A , a generic surgical anastomosis stapling instrument or stapling device for performing a circular anastomosis stapling operation is shown, with the figure taken from the U.S. Pat. No. 5,271,544 “Surgical anastomosis stapling instrument”, assigned to Ethicon, Inc., Somerville, N.J., and incorporated herein by reference in its entirety for all purposes. Various modifications and iterations of the shown stapling device are known in the art, having similar features. The circular anastomosis surgical stapling instrument  50  includes a distal stapling head assembly  60  connected by a longitudinally curved support shaft assembly  70  to a proximal actuator handle assembly  80 . The stapling instrument includes an anvil assembly or anvil  100  which is slidable longitudinally relative to the stapling head assembly  60  and mounted on an axially extending moveable shaft  104 . An optional rotatable adjusting knob  82  is provided at the proximal end of the actuator handle assembly  80  for adjusting the spacing between the stapling head assembly  60  and the anvil assembly  100 . An optional movable indicator  84  is visible through an optional window  85  on top of the handle assembly  80  to indicate the staple height selected by rotation of the adjusting knob  82 . The indicator  84  is movable indicating that the anvil gap is within a desired operating range of the stapling instrument  50 . The position of the indicator  84  also indicates whether the selected staple height is large or small. 
         [0036]    A staple actuating lever  86  is pivotally mounted on the actuator handle assembly  80  for driving the surgical staples from the stapling head assembly  60  when the anvil assembly  100  is closed to provide the desired staple height. A pivotal latching member  88  is mounted on the handle assembly  80  for locking the staple actuating lever  86  against movement to preclude actuation of the stapling head assembly  60  when the anvil gap is outside of a predetermined range. 
         [0037]    In a typical design of circular anastomosis surgical stapling instrument  50 , as schematically shown in  FIG. 1B , anvil  100  can be connected in a lockable way to axially extending moveable shaft  104  extending from stapling head  60 . Anvil  100  connection to shaft  104  is typically established via anvil pin  101 , locking for instance through engagement of a shaft  104  tip  105  into a sleeve  102  formed in anvil pin  101 . Other ways of engaging and locking anvil  100  to shaft  104  are known, but all involve lockable engagement of anvil pin  101  to shaft  104 . 
         [0038]    Referring now to  FIG. 1C , anvil  100  is shown lockably connected to shaft  104  through engagement of tip  105  into a sleeve  102  while  FIG. 1B  is illustrating anvil  100  not connected to shaft  104 . 
         [0039]    The anastomosis can be performed by a variety of techniques known in the art. In one exemplary technique, low anastomosis of colon to rectum using the anastomotic stapler is performed. Briefly, after stapler  50  is inserted through the anus, the descending colon is fixated around anvil  100 , with purse string sutures tied around the shaft and the rectal stump is fixated around stapling head  60  with purse string sutures also tied around the shaft. Anvil  100  is then pulled towards stapling head  60  and then the staples are deployed to join the tissue of the descending colon and rectal stump at their respective serosal surfaces, with simultaneous action of circular scalpel (not shown) within stapler  50  cutting away excessive tissue (inverted bowel) closest to shaft, resulting in anastomosis. Stapler  50  is then removed. 
         [0040]    According to the present invention, application of therapeutic material refers to subserosal injection into the tissue, prior to the joining of the tissue by staples. The device of the present invention delivers therapeutic agents to the subserosa of the large intestines at the anastomotic site prior to performing the anastomosis. Therapeutic material or therapeutic agent refers to any medically useful substance or combination of substances, which can improve tissue viability, including drugs, enzymes, growth factors, peptides, proteins, nutrients, excipients, and any other injectable pharmaceutical agents. Examples of therapeutic agents are also autologous cells and fibrinogen. 
         [0041]    The delivery head of the present invention allows for direct subserosal delivery of therapeutic agents to the regions which have not yet been stapled. The delivery of therapeutic agents is performed beneath the serosa layer on both the anvil and stapling head side prior to staple deployment. Introducing the therapeutic agents before stapling overcomes the problem of accessibility and improves the surgeon&#39;s ability to provide complete (360 degree) coverage around the anastomotic joint. The application of therapeutic material to the staple interface region prior to stapling can still be supplemented with a topical application of agents to the serosal layer after stapling if desired. 
         [0042]    Clinical evidence shows the formation of a full wall intestinal defect at or near the anastomotic site may occur as soon as 1-2 days post-op, with typical time period when the clinical symptoms of leaks occur being from 1 to 5 days post-op. See, for example, K. Jönsson, H. Jiborn, B. Zederfeldt, “Breaking strength of small intestinal anastomoses”, The American Journal of Surgery, v. 145, pp. 800-803, 1983; Y.-H. Ho, M. A. T. Ashour, “Techniques for colorectal anastomosis”, World Journal of Gastroenterology, 16(13), pp. 1610-1621, 2010. 
         [0043]    Referring now to  FIGS. 2A and 2B , anastomotic joint  26  of tubular proximal lumen  20  and distal lumen  22  is schematically presented in a longitudinal cross-section, with rows of staples  32  and  33  arranged in concentric circles around anastomosis opening  27  as shown in  FIG. 2C  in a cross-sectional frontal view. Proximal lumen  20  and distal lumen  22  are joined at serosal (external) surfaces  24 . 
         [0044]    According to one embodiment of the present invention, the targeted sub-serosal areas for the delivery of therapeutic agents are shown schematically as delivery zones  40  ( FIG. 2A ), continuously covering areas immediately around and between staples  32  and  33  and extending from close to anastomosis opening  27  to beyond larger diameter staple row  33  and towards tubular sections  25  of proximal lumen  20  and distal lumen  22 . Delivery zones  40  are further shown in  FIG. 2D  and are targeting all subserosal area of tissue of proximal lumen  20  and distal lumen  22  (not shown in  FIG. 2D ) which are forming anastomotic joint  26 . 
         [0045]    In another embodiment of the present invention, targeted sub-serosal areas for the delivery of therapeutic agents are shown schematically as delivery zones  42  shown in  FIG. 2B  covering areas only immediately around and between staples  32  and  33 , further shown in  FIG. 2G  and targeting subserosal area of tissue of proximal lumen  20  and distal lumen  22  (not shown in  FIG. 2G ) immediately around and between staple rows  32  and  33 . 
         [0046]    In yet another embodiment of the present invention, targeted sub-serosal areas for the delivery of therapeutic agents are shown schematically as intermittent delivery zones  46  shown in  FIG. 2E  covering intermittent areas immediately around and between staples  32  and  33  and extending from close to anastomosis opening  27  to beyond larger diameter staple row  33 . 
         [0047]    In still another embodiment of the present invention, targeted sub-serosal areas for the delivery of therapeutic agents are shown schematically as delivery zones  48  shown in  FIG. 2F  covering areas only beyond larger staples row  33 . 
         [0048]    It is apparent from the above description that in various embodiments of the present invention delivery zones of the therapeutic agent into subserosal areas are contemplated around and between staples and also beyond rows of staples, generally into tissues which are in contact with other tissues in the anastomotic joint and into tissues which are subject to formation of ulcerations and tissue necrosis within and around anastomotic joint. 
         [0049]    Delivery heads of the present invention are designed to deliver therapeutic agents into subserosal delivery zones, as described above, immediately before the formation of anastomotic joint. 
         [0050]    Referring now to  FIG. 3 , one embodiment of delivery head  300  of the present invention is schematically presented as comprising an elongated generally ring-shaped or cylindrical body  310  having front side  320  and rear side  330 , with an array or group of microneedles  350  disposed on front side  320  around centering cylindrical opening  340  having diameter matching, but larger than the external diameter of anvil pin  101  and/or shaft  104  so that anvil pin  101  and/or shaft  104  can slidably enter centering cylindrical opening  340 . Centering cylindrical opening  340  serves as centering aperture for positioning delivery head  300  onto anvil pin  101  and/or onto shaft  104  and for sliding delivery head  300  on anvil pin  101  and/or on shaft  104 . Microneedles  350 , in one embodiment, are arranged in two concentric array or groups  351  and  352  around centering cylindrical opening  340 . Length L of delivery head  300  is from about 5 mm to about 250 mm, more preferably from 20 mm to about 100 mm. Microneedles  350 , in other embodiments, can be arranged around centering cylindrical opening  340  in various configurations, including random, concentric with one, two, three, or more concentric array or groups, checkered array, spiral array, or any other configuration, all assuring complete and uniform coverage of front side  320  with microneedles  350 . 
         [0051]    Referring now to  FIGS. 4A and 4B , a cross-sectional view of the embodiment of device  300  shown in  FIG. 3  is presented, with hollow microneedles  350  arranged in three concentric rows and having microneedle channels  355  through the whole length of microneedle  350  and connecting microneedles  350  to compartment  360  positioned inside body  310  in proximity to front side  320 . Compartment  360  is, in one embodiment, a ring-shaped chamber situated under surface of front side  320 ; compartment  360  is in fluid communication with all microneedles  350 . Compartment  360  is connected to port  380  via channel  370 . Port  380  is shown situated on rear side  330 , but is can be also positioned on side wall  315  of body  310  as shown in  FIG. 4B . Port  380  is used to connect a cannula (not shown) to deliver therapeutic agents into compartment  360  and from compartment  360  into microneedle channels  355  within hollow microneedles  350  and from microneedles  350  into tissue (not shown). Centering cylindrical opening  340  optionally has a cavity  342  having an increased diameter open to front side  320 . The depth of optional cavity  342  is from about 3 mm to about 75 mm as measured from front side  320 , preferably from 5 mm to 30 mm. The diameter of optional cavity  342  is at least 20% larger than the external diameter of anvil pin  101  and/or shaft  104 . In one embodiment, the diameter of optional cavity  342  is approximately equal to or smaller than the diameter of anastomosis opening  27 . In one embodiment, the diameter of optional cavity  342  is approximately equal to or smaller than the smaller diameter staple row  32  as shown in the series of  FIG. 2 . 
         [0052]    Referring now to  FIG. 5A , a cross-sectional view of an embodiment of device  300  shown in  FIG. 4  is presented, with array or group of hollow microneedles  350  having microneedle channels  355  in three concentric rows  351 ,  352 ,  353 . Other arrangements of microneedles  350  into an array or group are contemplated, such as checkered arrangement (not shown). The microneedles can be also distributed in an uneven arrangement as single or partial rings or shapes. Optional flange-shaped handles  314  are disposed on rear side  330  to facilitate manual handling of delivery head  300 . 
         [0053]    Referring now to  FIG. 5B , a cross-sectional view of an embodiment of device  300  is presented, with array or group of hollow microneedles  350  having microneedle channels  355  comprising only one circular array or group comprising one row  352  of microneedles  350 . 
         [0054]    Referring now to  FIG. 5C , a view of front side  320  of device  300  is shown, corresponding to embodiment of  FIG. 5B , having array or group of hollow microneedles  350  having microneedle channels  355  comprising only one circular array or group comprising one row  352  of microneedles  350 . Compartment  360  is shown by dashed lines as being situated below surface of front side  320  and in fluid communication with microneedle channels  355 . 
         [0055]    Referring now to  FIG. 6A , in preparation for use, after stapling head  60  was installed in the proximal lumen  20  and prior to deploying staples forming anastomotic joint, delivery head  300   a  is fitted over shaft  104  with shaft  104  slidably entering centering cylindrical opening  340 . Shaft  104  is used as a guide to advance delivery head  300   a  towards tissue areas  28  of proximal lumen  20  which are about to be joined by stapling in forming anastomotic joint, with microneedles  350  facing towards tissue areas  28 . 
         [0056]    Referring now to  FIG. 6B , delivery head  300   a  is shown further slidably advanced over shaft  104  and is pushed against stapling head  60  with microneedles  350  piercing serosal surface  24  and entering subserosal tissue of tissue areas  28 . Therapeutic agent is then injected into channel  370  through port  380  using any suitable injection device, such as syringe (not shown); therapeutic agent advances into compartment  360  and into microneedle channels  355  within microneedles  350 , with therapeutic agent entering subserosal tissue of tissue areas  28 . Injected therapeutic agent can form microdroplets  358  in the vicinity of microneedles  350  within tissue areas  28 . Therapeutic agent can then at least partially disperse or dissipate within subserosal tissue of tissue areas  28  immediately prior to deploying staples forming anastomotic joint. In one embodiment, therapeutic agent is pre-injected into channel  370  through port  380 , thus pre-filling compartment  360  prior to microneedles  350  piercing serosal surface  24  and entering subserosal tissue of tissue areas  28 , in which case the air inside channel  370  and compartment  360  is removed prior to microneedles  350  entering tissue. 
         [0057]    Referring now to  FIG. 6C , after the delivery of therapeutic agent, delivery head  300   a  is removed from shaft  104 , leaving microdroplets  358  of therapeutic agent in subserosal tissue areas  28 . 
         [0058]    In a similar fashion, and referring now to  FIG. 6D , in preparation for use, after anvil  100  was installed in the distal lumen  22  and prior to deploying staples forming anastomotic joint, delivery head  300   b,  having substantially similar design to delivery head  300   a,  is fitted over anvil pin  101 , with anvil pin  101  slidably entering centering cylindrical opening  340 . Anvil pin  101  is used as a guide to advance delivery head  300   b  towards tissue areas  28  of distal lumen  22  which are about to be joined by stapling in forming anastomotic joint, with microneedles  350  facing towards tissue areas  28 . 
         [0059]    Referring now to  FIG. 6E , delivery head  300   b  is further slidably advanced over anvil pin  101  and is pushed against anvil  100  with microneedles  350  piercing serosal surface  24  and entering subserosal tissue of tissue areas  28 . Therapeutic agent is then injected into channel  370  through port  380  using any suitable injection device, such as syringe (not shown); therapeutic agent advances into compartment  360  and into microneedle channels  355  within microneedles  350 , with therapeutic agent entering subserosal tissue of tissue areas  28 . Injected therapeutic agent can form microdroplets  358  in the vicinity of microneedles  350  within tissue areas  28 . Therapeutic agent can then at least partially disperse or dissipate within subserosal tissue of tissue areas  28  immediately prior to deploying staples forming anastomotic joint. 
         [0060]    Referring now to  FIG. 6F , after the delivery of therapeutic agent, delivery head  300   b  is removed from anvil pin  101 , leaving microdroplets  358  of therapeutic agent inside tissue areas  28 . 
         [0061]    After the delivery of the therapeutic agent, and removal of delivery heads  300   a  and  300   b  from anvil pin  101  and shaft  104 , anvil pin is lockably connected to shaft  104  through engagement of tip  105  into sleeve  102  as shown in  FIGS. 1B and 1C , and anastomotic stapling is performed as usual by deploying staples from the circular anastomosis surgical stapling instrument. Advantageously, tissue areas forming anastomotic joint have been treated with therapeutic agent, improving tissue viability and preventing ulceration and tissue necrosis. 
         [0062]    Referring now to  FIGS. 7A-7C , additional embodiments of delivery head  300  are presented in a schematic cross-sectional view.  FIG. 7A  shows an embodiment of delivery head  300   c  having a circumferential lip  312  comprising a raised ridge around the outside circumference of front side  320 . Optional lip  312  is adapted to surround proximal or distal lumen positioned on anvil or on stapling head. 
         [0063]      FIG. 7B  shows an embodiment of delivery head  300   d  whereby body  310  has generally a conical shape with diameter of rear side  330  smaller that is less than the diameter of front side  320 , such as 20%, 40%, or 70% smaller, preferably 50% smaller. 
         [0064]      FIG. 7C  shows an embodiment of delivery head  300   e  whereby body  310  has generally a conical shape similar to the embodiment of  FIG. 7B , further having a conical shaped cutout  343  between centering cylindrical opening  340  and a second area  343  having an increased diameter relative to opening  340 . 
         [0065]    Referring now to  FIG. 8 , it is shown an embodiment of delivery head  300   f,  whereby body  310  comprises a ring-shaped housing  316  connected by a plurality of supports  318  to an axially aligned centering ring  317 . Delivery head  300   f  preferably has at least two supports  318  between housing  316  and centering ring  317 , more preferably three or four supports  318  are used, with three supports  318  shown in  FIG. 8 . Ring-shaped housing  316  has hollow microneedles  350  disposed on front side  320 , optionally arranged in several arrays or groups such as arrays  351  and  352 . Opening  342  in the ring of ring-shaped housing  316  is an area defined by having a diameter that is at least 20% larger than the external diameter of anvil pin  101  and/or shaft  104  (neither shown in  FIG. 8 ). Ring-shaped housing  316  has internal compartment  360  (not shown in  FIG. 8 ) in fluid communication with hollow microneedles  350  and with channel  370  (not shown in  FIG. 8 ) inside at least one of supports  318  and within at least a portion of centering ring  317 . Channel  370  (not shown in  FIG. 8 ) terminates in port  380  adapted for connecting to a pressurized source of therapeutic agent, such as a syringe (not shown in  FIG. 8 ). Centering ring  317  has centering cylindrical opening  340  adapted for centering delivery head  300   f  on anvil pin  101  and/or on shaft  104 . In one embodiment, length L of delivery head  300   f  is at least equal to the length of anvil pin  101  and/or on shaft  104 , in another embodiment length L is from 10% to 100% longer than anvil pin  101  and/or shaft  104 . In all embodiments, length L is selected so as to ensure that once delivery head  300   f  is positioned onto anvil pin  101  and/or onto shaft  104  and slidably advanced towards tissue areas  28 , anvil pin  101  and/or shaft  104  are situated within centering ring  317  for reliable centering. 
         [0066]    Referring now to  FIGS. 9A and 9B , embodiments of delivery heads  300   f  are shown in operation in conjunction with circular anastomosis surgical stapling instrument  50 . Arrows indicate the direction of advancing delivery heads  300   f  on anvil pin  101  ( FIG. 9B ) and on shaft  104  ( FIG. 9A ) towards tissue areas  28  on proximal lumen  20  and distal lumen  22  until microneedles  350  contact and pierce tissue areas  28 . Syringes  400  are shown connected to ports  380  via cannulas  410  enabling therapeutic agent (not shown) to be expressed from syringes  400  through cannulas  410  into ports  380  and further via channel  370  into compartment  360  and through hollow microneedles  350  into tissue areas  28 . After the delivery of therapeutic agent into tissue areas  28 , delivery heads  300   f  are removed and shaft  104  is connected to anvil pin  101  and the stapling is performed. 
         [0067]    According to embodiments of the present invention, hollow microneedles  350  are from 50 microns to about 1500 microns in diameter, more preferably 100 to 1000 microns, such as 200 or 500 microns. Microneedle channels  355  are from about 25 microns to about 500 microns, more preferably 50 to 300 microns, such as 100 microns. According to embodiments of the present invention, hollow microneedles  350  are from 100 microns to about 2000 microns long, such as 500 microns or 1000 microns long. In certain embodiments, there are from about 10 to about 500 or 1000 microneedles on front side of the delivery head, more preferably at least 20 microneedles, most preferably at least 50 or 100 microneedles arranged in one or several microneedle arrays or groups. 
         [0068]    According to one embodiment of the present invention, injection volume is about 0.1-2 ml per injection, more preferably 0.2-0.5 ml per injection. 
         [0069]    According to embodiments of the present invention, diameter of delivery heads of the present invention is selected to fit into surgical anastomosis stapling instrument, and is ranging from about 100 mm to about 30 mm, more preferably from 15 mm to 28 mm, such as 21 mm, 24 mm, or 26 mm. The diameter of centering cylindrical opening  340  is from about 4 mm to about 10 mm, such as 5, 6, or 7 mm. 
         [0070]    Optional lip  312  extends from surface of front side  320  to lip height from about 1 mm to about 8 mm, preferably 2 mm to 5 mm, such as 4 mm. 
         [0071]    Referring now to  FIGS. 10A and 10B , an embodiment of the present invention is presented in a schematic cross-sectional view. As shown in  FIG. 10A , delivery head  305  comprises a cylindrical or ring-shaped hollow body  311  having front side  320  and opposing rear side  330 , and sidewall  313  with ring opening comprising centering cylindrical opening  340  and having optional lip  312 . A plurality of microneedles  350  are disposed on both front side  320  and rear side  330 , and compartment  360  is disposed inside the hollow body  311 . Microneedle channels  355  are in fluid communication with compartment  360  which is in turn in fluid communication with port  380 . Thickness T of delivery head  305  is from about 2 mm to about 10 mm, such a 6 mm. 
         [0072]    As shown in a schematic cross-sectional view in  FIG. 10B , in use, delivery head  305  is positioned on either shaft  104  or anvil pin  101  after which shaft  104  and anvil pin  101  are engaged. Prior to positioning delivery head  305  onto shaft  104  or anvil pin  101 , or after positioning, syringe  400  containing therapeutic agent is connected to port  380  via cannula  410 . Anvil  100  is then approximated to stapling head  60  by turning knob  82  resulting in delivery head  305  squeezed between anvil  100  and stapling head  60  resulting in microneedles  350  on both front side  320  and rear side  330  piercing tissue and entering tissue areas  28 , as shown in  FIG. 10C . Therapeutic agent is then expressed from syringe  400  and advances via cannula  410  into port  380  and then into compartment  360  and into microneedle channels and is injected into tissue areas  28 . After the injection is performed, the anvil pin is disengaged from shaft  104 , and delivery head  305  is removed. Anvil pin is then re-engaged with shaft  104  and the stapling is performed. 
         [0073]    Referring now to  FIG. 10D , an embodiment of the present invention is presented in a schematic cross-sectional side view. Also referring to  FIGS. 10E and 10F , the same embodiment is shown in a schematic prospective view and in a schematic prospective cross-sectional view respectively. In the view shown in  FIG. 10F , compartment  360  is shown in hollow body  311 . Delivery head  306  has a substantially similar construction to delivery head  305  shown in  FIGS. 10A-C , with the difference being the ring thickness T of ring shaped delivery head  306  being larger compared to thickness of delivery head  305 . Thickness T of ring shaped delivery head  306  device is from 10 mm to 20 mm, such as 15 mm. 
         [0074]    Referring now to  FIG. 10G , as shown in a schematic cross-sectional view, in use, delivery head  306  is engaged with syringe  400  and anastomosis surgical stapling instrument  50  in a similar fashion to the earlier shown embodiment of  FIG. 10C . 
         [0075]    Referring now to  FIGS. 11A ,  11 B and  11 C, further alternative embodiments of the present invention are presented in schematic prospective views. As shown in  FIG. 11A , embodiment of delivery head  306   a  having generally a similar design to device  306  of  FIG. 10 , comprises half-ring hollow bodies  311   a  and  311   b  which when joined together via magnetic strips  395  (only visible on half-ring hollow body  311   b ) form delivery head  306   a  having ring shape similar to device  306  of  FIG. 10 . Delivery head  306   a  can be positioned onto shaft  104  connected to anvil pin  101  and also removed from shaft  104  connected to anvil pin  101  by separately positioning and removing hollow bodies  311   a  and  311   b.  Thus delivery head  306   a  can be assembled from hollow bodies  311   a  and  311   b  directly on shaft  104  connected to anvil pin  101  and can also be removed from shaft  104  connected to anvil pin  101  by separately removing hollow bodies  311   a  and  311   b.  Both hollow bodies  311   a  and  311   b  have ports  380   a  and  380   b  for delivery of therapeutic agent through ports  380   a  and  380   b.    
         [0076]    As shown in  FIG. 11B , another embodiment of delivery head  306   b  having generally a similar design to device  306   a,  comprises half-ring hollow bodies  311   a  and  311   b  which when joined together via pins  396  entering matching apertures  397  form delivery head  306   b  having ring shape similar to device  306  of  FIG. 10 . Thus delivery head  306   b  can be assembled from hollow bodies  311   a  and  311   b  directly on shaft  104  connected to anvil pin  101  and can also be removed from shaft  104  connected to anvil pin  101  by separately removing hollow bodies  311   a  and  311   b.  Both hollow bodies  311   a  and  311   b  have ports  380   a  and  380   b  for delivery of therapeutic agent through ports  380   a  and  380   b.  Optionally, in an alternative embodiment, only one port  380   a  is used and the therapeutic agent, after entering hollow body  311   a  through port  380   a,  can transfer into hollow body  311   b  via one or more pins  396  which in this embodiment are hollow pins having channels inside. Port  380   b  is not used in this case. 
         [0077]    As shown in  FIG. 11C , in another embodiment, delivery head  306   c  having generally a similar design to device  306   a,  comprises half-ring hollow bodies  311   a  and  311   b  which are joined at hinge  398 . Hollow bodies  311   a  and  311   b  form delivery head  306   c  which can open and close around shaft  104  connected to anvil pin  101  in a clam-shell like fashion, opening and closing at hinge  398 . Thus delivery head  306   c  can be positioned directly on shaft  104  connected to anvil pin  101  and can also be removed from shaft  104  connected to anvil pin  101  by opening and closing delivery head  306   c  in a clam-shell like fashion at hinge  398 . 
         [0078]    Advantageously, and as can also be seen from  FIGS. 6 ,  9 ,  10 B,  10 C,  10 G, the delivery of therapeutic agent is performed prior to deploying staples, i.e. into non-compressed tissue, or under low compression of tissue. Low compression of tissue is defined as tissue being compressed less relative to the compression of tissue under deployment of staples. Thus therapeutic agent can potentially penetrate the tissue and is expected not to be pushed from the tissue due to high compressive forces. Advantageously, therapeutic agent is delivered into both proximal and distal lumens of tissue. 
         [0079]    Advantageously, because therapeutic agent delivery is performed prior to and independently of staples deployment, more area of the tissue is available for delivering the agent, as microneedles do not interfere with staples and larger density of needles is possible. Areas of tissue that are about to be penetrated by staples can also be treated. Thus tissue can be treated with higher uniformity and with a higher density of injections of therapeutic agent using the microneedles of the present invention. In certain embodiments, there are from 10 to 500 microneedles on front side of the delivery head, more preferably at least 20 microneedles, most preferably at least 50 microneedles arranged in one or several microneedle arrays. An equal number of microneedles can be disposed on the rear side of embodiments shown in  FIGS. 10 and 11 . 
         [0080]    Advantageously, because therapeutic agent delivery is performed prior to staples deployment, therapeutic agent can potentially redistribute in the tissue more uniformly during the time period between the delivery of the therapeutic agent and deployment of staples. The time period from therapeutic agent delivery through microneedles to the deployment of staples is from about 10 seconds to about 10 minutes, more preferably from about 20 seconds to about 3 minutes, most preferably 1 to 2 minutes. 
         [0081]    While the invention has been described above with reference to specific embodiments thereof, it is apparent that many changes, modifications, and variations can be made without departing from the inventive concept disclosed herein. Accordingly, it is intended to embrace all such changes, modifications, and variations that fall within the spirit and broad scope of the appended claims. All patent applications, patents, and other publications cited herein are incorporated by reference in their entirety.