Patent Application
20240307706
This application is directed to a device for insertion into body lumens to provide protection and/or support to the lumens/tissue during and/or after treatment such as radiation.
The gastrointestinal (GI) tract extends from the esophagus to the anus and serves many functions, including nutrition, hydration, and disease prevention. Resection of a portion of the GI tract, such as esophagus, stomach, small intestine, large intestine or colon, is performed on a patient under general anesthesia. An incision is typically made in the abdomen, chest or neck and a diseased portion is removed. The healthy ends that remain are sewn or stapled together and the incision is closed through the procedure known as anastomosis.
Gastrointestinal doctors use colonoscopy or endoscopy procedures to treat the colon or any GI tract lumen to remove cancerous or precancerous polyps. Such procedures include polypectomy or endoscopic mucosal resection (EMR) to remove such sections of cancerous or precancerous tissue. After such procedures, radiation therapy is sometimes provided to shrink or destroy any cancer cells remaining which can proliferate and create risks to the patients. Such forms of radiation include external beam radiotherapy, unsealed source radiotherapy wherein a therapeutic is localized injected to the body, brachytherapy where a sealed radiation source is placed inside or next to the area requiring treatment, etc. In each of these radiation applications, the tissue can be weakened and thus the integrity of the tissue can deteriorate which can have adverse effects.
That is, in certain instances, radiation in attempting to shrink the tumor, damages healthy surrounding tissue which can weaken the body lumen. This is especially the case since the radiation therapy is applied over a period of time, either intermittently or continuously. In some cases, the weakened tissue can result in leakage of the body lumen or a perforation. Leakage may lead to contamination of the peritoneal or thoracic cavity, sepsis, morbidity and even death and perforation can also have adverse effects. The radiation can also weaken the anastomotic site.
A perforation results from insult or injury to the mucosa of the bowel wall resulting from a violation of the closed system. This can be from an ulceration or trauma or iatrogenic cause (instrumentation). Bowel perforation can be secondary to many factors, most commonly inflammation, infection, obstruction, trauma, or invasive procedure. Diverticulitis is an example of a perforation. Anastomotic leakage is another. This exposes the structures within the peritoneal cavity to gastrointestinal contents. Patients presenting with abdominal pain and distension, and can be life-threatening due to the risk of developing infections such as peritonitis. Surgery is often necessary to close the perforation and/or divert the enteric contents away from the area of the perforation via a colostomy for example.
It would be advantageous to provide a device for use with surgical procedures for early colon or other GI tract cancers removed by colonoscopy and also early cancers removed via endoscopy requiring post-surgery radiation which would protect the tissue undergoing radiation, i.e., prevent or at least limit, the effect of tissue damage during radiation.
Advances in minimally invasive procedures allow entry into body lumens without major surgery. It would be advantageous to provide such device to protect tissue undergoing radiation which could be inserted minimally invasively.
Commonly owned U.S. Pat. No. 8,894,699 (hereinafter the '699 patent) discloses devices which effectively addressed reducing the risk of leaks at the anastomotic site. The devices disclosed are in the form of a covered stent providing a scaffold. An impermeable layer is placed over and attached to the scaffold. The device is inserted between or into the lumen ends to be anastomosed to provide stability and/or structure to the anastomosed lumen.
The inventor of the '699 patent, along with the other inventor of the present application, conceived of modifications to the device of the'699 patent which could provide advantages in certain clinical applications, as well as conceived of new advantageous uses of the devices to support tissue during cancer treatment, such as during radiation, as well as provide support after radiation therapy.
The device can protect the tissue and provide a shield from harmful gamma rays. The device can be placed minimally invasively during surgery that provides anastomotic protection from the harmful effects of radiation such as during brachytherapy procedures.
In one aspect, the present invention provides a protective device in the form of a biodegradable tubular structure to provide a support for the body lumen which could be damaged during radiation. An adhesive can be utilized to attach the tubular structure to the body lumen and the adhesive can also provide a sealant. The device can be placed prior to the radiation treatment, and does not interfere with the treatment. The device can be left in place after the radiation to provide support during intervals between radiation, and can be left in after the radiation treatment/therapy is complete. The device is inserted minimally invasively and because of it being biodegradable, it does not require another procedure for removal. It degrades as healthy tissue growth is restored.
The tubular device of the present invention is in the form of a straw with a thin wall and a lumen extending therethrough, and has an open proximal and distal end to enable flow therethrough. The tubular device in some embodiments is shaped like a condom (with a rim/rib top) or can be a colon-shaped device. (“Top” referring to the portion/region closer to the head of the patient).
In another aspect of the present invention, the tubular device can be made of tissue engineered material, e.g., from tissue generated organs, and placed in the colon to provide extra support to seal. In some embodiments, the tissue generated material comprises colon cells.
In another aspect of the present invention, the biodegradable.
In accordance with another aspect of the present invention, a method to support a body lumen during radiation treatment is provided comprising the steps of a) positioning a tubular straw like device in a body lumen of the gastrointestinal tract prior to treatment; b) securing the device to the intestine utilizing an adhesive; and c) leaving the device in place after the radiation treatment to enable it to degrade.
The device in some embodiments can also include a treatment or healing substance, e.g., a drug, adhered thereto.
In accordance with another aspect of the present invention, a method to add integrity to a tissue site undergoing radiation is provided comprising the steps of a) positioning a tubular straw like device in a lumen of the body region; and b) securing the device to the lumen utilizing an adhesive, the device providing support for the tissue region weakened by the radiation.
The foregoing methods utilize in some embodiments a tubular device having an enlarged rim providing a diameter larger than other regions of the device. The rim is at the top portion of the device and in some embodiments provides a radial force against the tissue, e.g., colon wall, to help secure the device in place. The device can be held in place by an adhesive. In preferred embodiments, the adhesive utilized has a dual function: adhering the device to the tissue, e.g., luminal wall, and providing a seal to prevent unwanted flow.
In some embodiments, the device is further secured by one or more sutures.
In accordance with another aspect of the present invention the device is composed of a tissue engineered material and held in place at the rim by an adhesive.
So that those having ordinary skill in the art to which the subject invention appertains will more readily understand how to make and use the apparatus (device) disclosed herein, preferred embodiments thereof will be described in detail hereinbelow with reference to the drawings, wherein:
As noted above, commonly owned U.S. Pat. No. 8,894,699, incorporated herein by reference in its entirety, and having a common inventor with the present application, disclosed devices which effectively addressed leakage at the anastomotic site. The devices disclosed are in the form of a covered stent providing a scaffold inserted between or into the lumen ends to be anastomosed to provide stability and/or structure to the anastomosed lumen.
The inventor of the '699 patent, along with the other inventor of the present invention, conceived of modifications to the device which could provide advantages in certain clinical applications, as well as conceived of new advantageous uses of the device, which are described in detail below.
The device of the present invention provides a tubular structure, also referred to herein as a straw-like structure. The tubular straw-like structure is impermeable and preferably composed of a biodegradable material which will degrade within the body after a period of time. The tubular structure in some embodiments provides structure and/or stability to the body lumens which can thereby protect the tissue undergoing radiation therapy. The tubular structure has a thin wall and a lumen extending therethrough, and has an open top and bottom end. “Top” and “bottom” as used herein refer to orientation wherein top is closer to the patient's head and bottom is further from the patient's head. Also, top and bottom as used herein relates to direction of flow of body fluids or substances, e.g., the stool passes from the top to bottom. Proximal as used herein can also refer to the top portion and distal refer to the bottom portion, also relating to flow/passage.
The tubular structure can be formed of one piece which provides the advantages of ease of manufacture and more flexibility as opposed to the use of covered stents which need to have an impermeable cover attached to the inner structure, e.g., frame.
The device can be used in a method to protect tissue in the gastrointestinal tract of a patient during radiation therapy, the method comprising positioning a biodegradable device to cover a perforation at a perforation site on a tissue of a patient prior to applying radiation therapy, closing the perforation through surgery, and securing the biodegradable device to cover the perforation site, so that the biodegradable device protects the tissue adjacent to the perforation site during radiation therapy. Wherein the biodegradable device is a biodegradable tubular straw or surgical patch. The surgical patch is a medical device made of tissue engineered materials designed to cover, repair, or augment damaged or weakened tissue or organs during surgery.
In some embodiments, the tubular device of the present invention is used with anastomosis of two body lumens, such as two portions of the intestine, where radiation is applied after the anastomosis to shrink or destroy any remaining cancerous microcells remaining after resection of the intestine portion. In other embodiments, the tubular device is used in an area where a poly or cancerous tumor has been removed from the body lumen and the surrounding tissue is subject to radiation therapy to shrink or destroy any remaining cancerous microcells remaining after polyp or tumor removal. Various other clinical applications of the tubular straw-like of the present invention are also contemplated.
For example, gastrointestinal doctors use colonoscopy or endoscopy procedures to treat the colon or any GI tract lumen to remove cancerous or precancerous polyps. Such procedures include polypectomy or endoscopic mucosal resection (EMR) to remove such sections of cancerous or precancerous tissue. After such procedures, radiation therapy is also provided to shrink or destroy any cancer cells remaining which can proliferate and create risks to the patients. Such forms of radiation include external beam radiotherapy, unsealed source radiotherapy wherein a therapeutic is localized injected to the body, brachytherapy where a sealed radiation source is placed inside or next to the area requiring treatment, etc. In each of these radiation applications, the tissue can be weakened and thus the integrity of the tissue can deteriorate which can have adverse effects. The device of the present invention protects the tissue from harmful effect of radiation, e.g., to shield the tissue from harmful gamma rays.
Thus, the device of the present invention can function to a) shield the tissue from harmful rays of radiation therapy; and b) maintain the structural integrity of the body lumen which would otherwise be weakened by the radiation therapy.
Referring now to the drawings and particular embodiments of the present disclosure, wherein like reference numerals identify similar structural features of the devices throughout the several views, the device (stent) of a first embodiment of the present invention is designated generally by reference numeral 10. Device 10 is in the form of a biodegradable straw and has a first open end 12 and a second opposite open end 14. The device can have various dimensions. First end 12 is dimensioned, i.e., outer dimension, to be inserted into opening a1 and into lumen a2 of first intestine portion a and second end 14 is dimensioned, i.e., outer dimension, to be inserted into opening b1 and into lumen b2 of second intestine portion b. Thus, the ID of the lumen is greater than the OD of the device 10.
In use, a lumen, such as a colon, is separated and a diseased, e.g., cancerous, portion is removed. After removal, the surgeon inserts one end of the tubular device 10 into one end of the separated lumen (or the separated lumen end is placed over the device 10). The second end of the tubular device 10 is then inserted into the other lumen (or the lumen end is placed over the device 10), and the two lumens are attached to each other by various methods such as suturing, stapling and/or use of an adhesive to create an anastomotic site.
The tubular device 10 can in some embodiments be inserted prior to anastomosis to act not only as a tissue shield during radiation but as a prophylactic measure against leakage and/or soilage to further the inconvenience and frequent complications associated with treating leaking anastomosed lumens. Additionally, the use of the device may prevent scarring and may eliminate or reduce constrictions (strictures) caused by closure of the lumen, such as by scarring or fusion.
In some embodiments, use of device 10 may promote healing in the affected area of the lumen.
Apparatus and methods of the present invention can be utilized for anastomosis after removal of cancerous tissue/body portions in various lumens of the body and the intestine in
In one embodiment, resection of a portion of the GI tract such as the esophagus, stomach, colon, small intestine or large intestine may be performed on a patient under general anesthesia to remove troublesome portions of luminal tissue, such as cancerous tissue. After resection, the separated lumen ends may be anastomosed, with the device 10 positioned in the luminal tissue. The device 10 is in place for radiation therapy at the anastomotic site
The device 10 (as well as devices 20 and 30 discussed below) is shown symmetrically shaped but asymmetrical shapes, such as the ends being of different sizes or configurations, are also contemplated as are shapes other than the cylindrical shape shown, e.g., funnel shaped, non-circular cross-section, etc. Additionally, the device may be configured for custom sizing and/or shaping to conform to the contours of the lumen.
The device is preferably non-expandable such that its transverse dimension is the same during insertion as well as during placement. However, in alternate embodiments, the device is collapsible/expandable such that it is inserted in a reduced diameter configuration and expands to a larger diameter placement configuration. Expansion can be for example by an inflatable balloon or by a phase change such as with shape memos polymeric materials.
The device can be configured to be of a size (or expandable to a size in embodiments where the device expands) to make contact with the surrounding luminal tissue, i.e., the internal wall of the lumen, for attachment and/or support. For example, where adhesive is applied to at least part of the external surface of the device and/or at least part of the internal surface of the luminal tissue, a balloon may provide a mechanism for holding the device 10 in place while the adhesive sets.
The device 10 comprises a biocompatible, biodegradable and/or bioabsorbable material. Once in place, it may disintegrate/degrade/resorb over time (once the lumens attach), and either become absorbed into or pass through the body so invasive mechanical removal is not necessary.
The tubular structure preferably provides a continuous outer wall (without openings) to provide a sealed structure along its length.
In some embodiments, the device can be composed of tissue engineered material. For example, the device can me made of cells of an organ such as colon cells.
In some embodiments, the device can be formed in the configuration of a condom with a rim (rib top) to providing a holding force to hold the device against the tissue/organ, e.g., colon, as shown in
The device 10 can include an adhesive applied thereon during the surgical procedure. The adhesive can be applied to a portion or to the entire external surface during the surgery and then the device inserted into intestinal portions as shown in
In the alternate embodiment of
The adhesive, in alternate embodiments, could be applied to device 10 prior to the surgery rather than during the surgery and activated during the procedure. That is, the adhesive could be applied to the external wall of the device 10 prior to the surgical procedure and then activated, e.g., via warming by body temperature, or by another device, to release the adhesive to provide adherence of the device 10 to the lumen walls a3, b3.
In the embodiment of
In the alternate embodiment of
Adhesive can be applied to the outer wall of the intestine sections a, b for attachment to the device 30. Alternatively, an adhesive can be applied to the inner wall of device 30 in lieu of adhesive application to the outer wall of sections a, b or in addition to adhesive application to the outer wall of sections a, b. Device 30 (and device 30′) can be made of the same material, can be of various symmetrical and asymmetrical forms, and function to provide structure in the same manner as device 10.
In another embodiment, the devices of the present invention can include a composition to promote healing, such as a growth factor, antimicrobial agent, antibody and/or the like. Growth factors comprise cellular proteins that assist in cellular proliferation and differentiation. Antimicrobial agents, including antivirals, antibiotics and antifungals, prevent harmful bacteria, viruses and/or other microbes from infecting the anastomosed site and interfering with the tissue healing and growth processes. Certain types of antibodies may be implemented to bind with foreign objects, such as bacteria and viruses that would be harmful to the healing site if not contained, e.g., preventing strains of bacteria causing leaks. Chemotherapeutic agents can be included on the device to diffuse into the tissue site. Thus, the device in addition to protecting tissue, can serve other healing and/or treatment functions, and its biodegradable aspect avoids having to remove the device after healing or treatment.
Various uses of the devices are contemplated herein. Some examples are provided below, it being understood the devices of the present invention disclosed herein can be used in clinical applications and in other parts/regions of the body in addition to those specifically disclosed herein.
In another application, the device be used in an area to be radiated to limit tissue damage. Thus, it can add integrity to the tissue site. This may enable radiation to start sooner since the device provides a support for previously weakened tissue.
Adhesives according to various aspects of the present invention may comprise any suitable material to attach, adhere and/or bond to living tissue. Adhesives may comprise natural, naturally derived and/or synthetic materials. The adhesive may comprise a gel, liquid and/or solid. Examples of adhesives that can be used include purified bovine serum albumin and glutaraldehyde, (sold commercially as Bioglue & by Cryolife Technology, Inc., Kennesaw Georgia). The adhesive can comprise polyethylene glycol, sold commercially as Duraseal R Sealant by Confluent Surgical, Inc., Waltham, Massachusetts pr Tiseel fibrin sealant. The adhesive applied could also be Puragel or Puracif.
In preferred embodiments, the adhesive utilized not only performs an adherence function but also forms a sealing function. Sealant surgical glue is one possible material that can be used.
Suitable methods of application of the adhesive may include spraying, topical application and/or injection. In one embodiment, a more viscous adhesive, such as Duraseal & Sealant, may be applied to decrease the setting time, thereby decreasing the time required for a surgeon to hold the ends of lumen together or the ends of a lumen against the device (scaffold). The adhesive may provide both a mechanism for attachment of lumen ends to each other after anastomosis, as well as a sealant. As described above, the adhesive may bond the device to the lumen ends and may seal the connection between the device and lumen ends. In yet another embodiment, the adhesive may be applied over the device and the lumen ends to both bond the lumen ends to the device, as well as provide a seal.
In one embodiment, once a biocompatible, biodegradable and/or bioabsorbable adhesive is in place it may be configured to disintegrate, degrade and either become absorbed into or pass through the body. For example, in an application where the lumen ends are configured to heal and reseal themselves, the adhesive may no longer be necessary to bond and/or seal the lumen, and it may desirable for the adhesive to be removed.
In alternate embodiments, a suture can be used in addition to or in lieu of the adhesive to help secure the device in place. The suture can be for example in the form a “T” that hooks in place. It can be placed in various regions of the device such as at the rim in devices like those of
The device of the present invention can be used in various methods. In one method to protect an intestine during radiation, the method includes a) positioning a tubular straw like device in a lumen of a first intestinal portion to be attached to a second intestinal portion at an anastomotic site, the tubular straw having a rim with an enlarged diameter; and b) securing the device to the intestine utilizing an adhesive, the rim blocking stool passage past the rim. In another method, a method to keep a lumen of an intestine open includes a) positioning a tubular straw like device across a narrowing in a lumen of the intestine; and b) securing the device to the intestine utilizing an adhesive, the device including a healing or treatment substance attached thereto. In another method, a method to support a tissue region during treatment such as radiation includes a) positioning a tubular straw like device across a region of the body blocked by a tumor; and b) securing the device to the intestine utilizing an adhesive top support the tissue during radiation, the device including a chemotherapeutic agent adhered thereto to shrink the tumor. In another method, a method to add integrity to a tissue site undergoing radiation includes a) positioning a tubular straw like device in a lumen of the body region; and b) securing the device to the intestine utilizing an adhesive, the device providing support for the tissue region weakened by the radiation.
Although the apparatus and methods of the subject invention have been described with respect to preferred embodiments, those skilled in the art will readily appreciate that changes and modifications may be made thereto without departing from the spirit and scope of the present invention as defined by the appended claims. Persons skilled in the art will understand that the various embodiments of the disclosure described herein and shown in the accompanying figures constitute non-limiting examples, and that additional components and features may be added to any of the embodiments discussed herein without departing from the scope of the present disclosure.
It will be understood by those skilled in the art that the above particular embodiments are shown and described by way of illustration only. The principles and the features of the present disclosure may be employed in various and numerous embodiments thereof without departing from the scope and spirit of the disclosure. The above-described embodiments do not restrict the scope of the disclosure.
Additionally, persons skilled in the art will understand that the elements and features shown or described in connection with one embodiment may be combined with those of another embodiment without departing from the scope of the present invention and will appreciate further features and advantages of the presently disclosed subject matter based on the description provided.
Throughout the present disclosure, terms such as “approximately,” “about”, “generally,” “substantially,” and the like should be understood to allow for variations in any numerical range or concept with which they are associated. It is intended that the use of terms such as “approximately”, “about”, “substantially”, and “generally” should be understood to encompass variations on the order of 25%, or to allow for manufacturing tolerances and/or deviations in design. For example, the term “generally parallel” should be understood as referring to configurations in which the pertinent components are oriented so as to define an angle there between that is equal to 180°+25% (e.g., an angle that lies within the range of (approximately) 1350 to (approximately) 225°.
The recitation of numerical ranges by endpoints includes all numbers within the range.
Although terms such as “first,” “second,” “third,” etc., may be used herein to describe various operations, elements, components, regions, and/or sections, these operations, elements, components, regions, and/or sections should not be limited by the use of these terms in that these terms are used to distinguish one operation, element, component, region, or section from another. Thus, unless expressly stated otherwise, a first operation, element, component, region, or section could be termed a second operation, element, component, region, or section without departing from the scope of the present invention.
Each and every claim is incorporated as further disclosure into the specification and represents embodiments of the present disclosure. Also, the phrases “at least one of A, B, and C” and “A and/or B and/or C” should each be interpreted to include only A, only B, only C, or any combination of A, B, and C.
The present application claims the benefit of the filing date of U.S. Provisional Patent Application No. 63/452,194, filed Mar. 15, 2023, the disclosures of which are hereby incorporated by reference herein in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63452194 | Mar 2023 | US |
