Description of The Preferred Embodiment
The present invention is an apparatus system and method that may be used to protect a first tissue from treatment performed on a second and adjacent tissue.
The principles and operation of the present invention may be better understood with reference to the drawings and the following description.
Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.
Treatment of body tissue by local release of chemicals or provision of radiation doses results in a chemical/radiation gradient between the treated tissue and normal tissue. Thus, the total radiation or chemical dose that can be applied to the tissue is affected by the dose that is inevitably emitted to adjacent normal tissue.
To span this treatment limit, a number of devices have been modified for tissue protection during local treatment of body tissue (see e.g. the background section). While the above-described prior art devices can be used to protect a tissue region from the deleterious effects of treatments applied to adjacent tissue, these devices either lack the shape necessary to effectively protect the tissue or are not effective in reducing the physiological effects on the removed tissue.
Thus, according to one aspect of the present invention, a tissue removal/separation device is provided that can be used to protect body tissue from the harmful effects of a treatment, such as heat or radiation treatment.
The term "removal/separation" as used herein refers to the removal of one tissue from another or the filling of the space between tissues by using a physical barrier.
The device of the invention comprises a balloon that is inflatable between a first tissue and a second tissue of the body of a subject, preferably a human being. As used herein, the terms "first tissue" and "second tissue" may denote two tissue types (e.g., prostate-rectum, colon-small intestine, bladder-colon, ovary-small intestine, colon-bladder, liver-gallbladder, lung-mediastinum, mediastinum-lung, breast-chest wall, esophagus-spine, thyroid-blood vessel, thyroid-throat, small and large intestine-retroperitoneal cavity, kidney-liver, pancreas-stomach, pancreas-spine, stomach-liver, stomach-spine, etc.) or different tissue regions of the same tissue type. It will be appreciated that in the latter case, the two tissue regions may naturally be adjacent and connected by fibres (e.g. the lung lobes) and can be separated by introduction of an incision.
In either case, the device of the invention is designed such that its expanded shape is selected to enable it to remove a first tissue from a second tissue. This physical separation, optionally in combination with the barrier effect of the device, protects the first tissue from the treatment applied to the second tissue.
As used herein, the term "treatment" when used in the context of first and second tissues is intended to mean any treatment that would be harmful to the non-treated tissue (e.g., the first tissue). Examples of treatment include radiation therapy, such as external radiation therapy using gamma rays, high energy photon beam therapy, electron beam therapy, photon beam therapy, neutron beam therapy, heavy particle number therapy, conformal 3d radiation therapy, Intensity Modulated Radiation Therapy (IMRT), interstitial brachtherapy (interstitial brachtherapy), or any combination thereof. Treatment may also include pharmacological treatment (topical) such as alcohol tissue ablation or hyperosmolar ablation using NaCl crystals or hyperosmolar solutions or physical tissue treatment (e.g., dissection).
Thus, the present invention provides a device for protecting tissue from the harmful effects of various treatments, including, but not limited to, externally provided radiotherapy such as ionizing or non-ionizing radiation (microwave therapy, radiofrequency therapy, high intensity focused ultrasound therapy, etc.), or interstitial therapy such as interstitial brachytherapy, interstitial thermal ablation, contact thermal ablation with hot fluids, high intensity focused ultrasound, termoredated rods, interstitial laser therapy with or without photosensitizers, cryotherapy, interstitial chemoablation, topical chemotherapy, etc. Such devices are also useful for interventional procedures, such as surgical resection, when blunt dissection and separation of tissue is difficult and can result in accidental injury to adjacent organs.
It will be appreciated that any number of the present devices may be used to fill a complex space in order to remove one tissue from another. The devices may be interconnected to maintain a functional protective structure. The multi-device structure may be adapted for physical separation in the abdominal cavity, with some of the interconnected devices serving as anchors for the body wall to resist movement and deflection of the structure.
Referring now to the drawings, FIGS. 1a-c illustrate one embodiment of the apparatus of the present invention, referred to herein as apparatus 10.
The device 10 includes a balloon 12 constructed of any biodegradable material. As used herein, the term bladder refers to any container having an internal volume when inflated and substantially no internal volume when deflated. Although fig. 1a-c illustrate a flattened balloon shape having an inflated state length L (fig. 1a, for example, from 1 to 20cm), an inflated state width W (fig. 1a, for example, from 1 to 20cm), and an inflated state thickness T (fig. 1c, for example, from 1 to 10cm), it will be appreciated that balloon 10 may be made in any shape suitable for uniform tissue removal, thereby reducing localized pressure on the removed tissue. Examples of capsule 12 shapes include, but are not limited to, pear shapes, spindle shapes, disc shapes, flat shapes, triangular shapes, and flat cylindrical shapes.
Reducing or minimizing the local pressure on the removed tissue is important because it ensures that sufficient blood flow is supplied to the removed tissue, thereby reducing the chance of ischemia. It will be appreciated that by selecting a shape that ensures such uniform pressure on the removed tissue, the present device overcomes the deficiencies of prior art balloon-shaped removal devices (e.g., U.S. patent No. 6852095) that create uneven pressure on the removed tissue (particularly on soft tissue) and are thus particularly prone to ischemia over prolonged periods of time.
Examples of the various bladder shapes that may be used by the apparatus 10 of the present invention are provided below in the examples section that follows.
The device 10 may be constructed of any biodegradable material, including, but not limited to, polymers, such as degradable polymers composed of hydroxy alkyds (hydroxy alkyds), polyorthoesters (polyorthoesters), polyphosphates (polyphosphates), polyanhydrides (polyanhydrides), and copolymers, and mixtures thereof. Of particular interest are homopolymers and copolymers made from lactic acid, glycolic acid, and caprolactone monomers (caprolactone). Preferred polymers are those that have proven safe in clinical use with predictable biodegradability, namely polylactide, poly (lactide-co-glycolide), poly (lactide-co-caprolactone) and polycaprolactone monomers. The polymer selected should be suitable for the intended material to be in vivo (in vivo) and the physical stability of the capsule 12. A biodegradable polymer capable of retaining its mechanical and physical properties for at least two months when designed as a thin-layer balloon is used to produce a balloon that needs to retain its mechanical and physical properties in vivo for at least two months. In addition, the polymer should be film-formed and flexible enough to enable the balloon 12 to be folded into a compact structure so as to be insertable into a tube to serve as a dispenser for the device 10 in vivo. The characteristics of the polymer component can be adjusted to any desired by mixing the various polymers or mixing the polymers with hydrophobic or hydrophobic additives that modify the characteristics of the polymers. Such additives may be plasticizers that increase the flexibility of the capsule 12, hydrophilic components such as poly (ethylene glycol) and minerals that increase hydrophilicity, and act as pore formers. The hydrophobic component may be triglycerides, fatty acids and esters, and other biodegradable polymers. The polymer structure and molecular weight play an important role in designing the desired properties of the polymer composition.
FIG. 1b shows the balloon 12 in a deflated (e.g., rolled) state, which is suitable for delivery using minimally invasive techniques (described further below). Fig. 1c shows the balloon 12 in a collision state, which can affect tissue removal or separation.
One suitable method for manufacturing the device 10 from a biodegradable polymer solution is provided below in example 1 of the examples section. In the method, the bladder 12 is formed into a seamless structure by dipping a water-soluble expanded bladder template in an organic polymerization solution and removing the formed polymer bladder from the template by dissolving the template in water.
Device 10 may include a bioadhesive coating or any other physical mechanism capable of reducing its mobility within the insertion site. This feature is important to reduce movement of the device 10 from the point of application and thereby ensure optimal protection of non-treated tissue.
Suitable bioadhesives include carboxymethylcellulose (CMC) and similar bioadhesives that allow for use in the human body. CMC may be used as a dry film on the bladder 12. Such a membrane improves the adhesion properties to tissue after insertion and water absorption. The balloon 12 may be configured with various surface structures such as small protrusions, grooves, ridges, hooks, ridges, or any combination thereof to increase the friction between the balloon 12 surface and the removed tissue when inflated without affecting the function of the device.
After insertion and positioning of the device 10, inflation of the balloon 12 is performed within the tissue. This insertion and positioning may be achieved using a guide (a suitable guide is described further below with reference to figure 1 d). After inflation, such guiding means may be kept attached to the device 10 during short procedures that require a period of several hours to provide treatment (e.g. thermal ablation), otherwise it may detach during longer procedures that require a period of days, weeks or even months to provide treatment (e.g. long radiation or interstitial procedures).
In the latter case, the device 10 is preferably constructed of a biodegradable material such that the device 10 degrades and is absorbed by the body over a predetermined period of time or after absorption of a predetermined dose of treatment (e.g., radiation). To be biodegradable, the device 10 is constructed of a biocompatible and bioabsorbable polymer and also has mechanical properties suitable for maintaining the desired shape within the tissue. Such polymers may be prepared by synthetic or natural methods, so long as the polymer is provided in sufficient purity for use in body tissues.
The polymers may be prepared by any combination of monomer units or natural semi-synthetic and synthetic biodegradable polymers and components. However, these units must be capable of biodegrading in vivo into non-toxic components that can be excreted or further metabolized.
The combination of units in the polymer must also be biocompatible and not cause an unintended biological response to implantation of the device 10. The polymer may be biodegraded in vivo by hydrolysis, enzymatic breakdown, intercellular degradation, or any other biologically indirect process. Because the need for tissue removal varies based on the type and length of treatment, it is desirable to have polymers with a range of degradation rates and a range of different properties. However, in general, preferred polymers will degrade in weeks to months, preferably less than one year. Examples of suitable biodegradable polymers that can be used to manufacture device 10 include, but are not limited to, biodegradable polyesters such as polylactide, poly (lactide-glycolide), poly (lactide-caprolactone monomer), and polycaprolactone monomer.
Preferably, the polymer is a polymer composed of a hydroxy acid monomer. The hydroxy hydrocarbon acid may optionally contain other functional groups and substitutions at any position, including heteroatoms between the hydroxy and hydrocarbon acid groups. The hydroxy acid may be polymerized using synthetic methods or preferably using biological methods. In the latter case, the hydroxy acid may be obtained in vivo from a non-hydroxy acid source. In Williams, s.f. and Peoples, o.p. chemtech, 26: suitable methods for preparing polyesters are described in 38-44(1996), Hocking, P.J.and Marchess, R.H. "biopolymers", G.J.L.Griffin, Ed., "Chemistry and Technology of Bioabsorbable Polymers", Chapman and Hall, London, 1994, pp.48-96.
The polymer may include one or more non-lipid bonds in the main polymer chain, which may be configured to be sensitive to cleavage in vivo. Suitable non-aliphatic linkages may include amides, polyurethanes, carbonates, iminocarbonates, oxalates, oxamates, orthoesters, anhydrides, phosphazenes, glycosides and ethers. Combinations of these bonds may be used to alter the rate of biodegradation, tailor the mechanics, surface, or other properties of the polymer, improve the handling and control of materials, and/or provide a means of adhering other compounds to the polymer (e.g., contrast agents or therapeutic agents described below).
Typical polymers suitable for making bladder 12 may include: d, L-polylactide, lactide-glycolide copolymers, PEG-PLA copolymers, polyesters and polyamides, and other biodegradable components that form a strong membrane that can remain in an expanded state for extended periods of time.
The time required for the polymer to degrade can be defined by the selection of the appropriate monomer. Differences in crystalline structure also change the degradation rate. A substantial loss of mass occurs when the polymer matrix degrades into oligomeric fragments that are small enough to be soluble in water. Thus, the initial polymer molecular weight affects the degradation rate. Degradable polymers comprising water-soluble polymer elements have been described previously, see, for example, Sawhney et al, (1990) "Rapid degraded polymers of dl-lactate, glycolide, and ε -lactate with increased hydrophilicity by hydrogel polymers", J.biomed.Mater.Res.24: 1397-1411. The degradation rate and thus the polymer selection is determined based on the use of the apparatus 10. For example, during cryotherapy and thermal ablation, polymers are selected that have a degradation time period of hours to one or two weeks; selecting a polymer having a degradation time period of 5-6 weeks during external beam irradiation; whereas during short-range therapy polymers with a degradation time period of several months are selected.
It will be appreciated that permanent implantation (preferably a degradable device) is particularly useful as it enables multiple treatments without the need for repeated insertion and positioning of the tissue protection device. Devices designed to enable such permanent implantation are particularly useful where the individual being treated is subjected to multiple treatments (e.g., radiation) over an extended period of time. In this case, repeated implantation of the tissue protection device and thus repeated distress of the individual may be avoided by using the device 10 of the present invention.
As described herein, the device 10 removes or separates one tissue from another when the balloon 12 is inflated.
Bladder 10 may be inflated using one of a variety of schemes. To enable inflation, the device 10 preferably includes a port 14 through which the balloon 12 can be inflated or deflated. The port 14 is preferably a small diameter port 1/5 to 1/100, preferably 1/5 to 1/20, in diameter, the expanded thickness or width of the balloon 12. The port 14 may be a fluid-filled port, in which case the bladder 12 may be inflated using a gas or liquid and deflated by evacuation. Alternatively, the port 14 may be used to introduce a solid elastic element capable of filling the balloon 12 so as to assume a semi-rigid expanded state. Such an element may be, for example, an elongate element 15 (e.g., a wire or thread having a diameter of 3-5 mm) which may be forced into a linear state 17 by pressure and thereby into the balloon 12 through the port 14, but which, when released naturally, assumes a coiled configuration 19 which forces the balloon 12 to assume an inflated state, as shown in fig. 1 d. Such wires may have a circular, oval, triangular, rectangular or star-shaped profile and may be solid or hollow. The profile may be uniform along the entire length of the wire, or may vary intermittently to allow for easier folding into the balloon 12. The capsule 12 may also be filled with beads optionally interconnected by wires or wires. It will be appreciated that such a wire or bead expands beyond the need for a balloon seal. Elongate member 15 may be made of a biocompatible and optionally biodegradable elastomeric material, such as polylactide, poly (lactide-co-glycolide), poly (lactide-co-caprolactone) and polycaprolactone monomers, or a Shape Memory Polymer (SMP) made of a multi-block copolymer of lactide and caprolactone monomers, for example, which may assume an extended state when heated and a coiled state when cooled to body temperature.
While any of the above-described solutions may be effectively used to inflate/deflate the bladder 12, it is now preferred to use liquid inflation because of its added advantages and ease of use.
The use of a liquid provides a number of advantages. It enables the balloon 12 to conform to the tissue being removed and thereby apply uniform pressure thereon. It enables the introduction of useful agents, such as contrast agents or therapeutic agents, into the capsule 12, and it can serve as an excellent physical barrier to heat or radiation by introducing radiation absorbing substances, such as iodinated agents or fluorocarbons.
Any fluid may be used to inflate the balloon 12, preferably the fluid used is biodegradable and physiological, such as 0.9% saline, Ringer's solution or Hartman solution. The use of physiological fluids is particularly advantageous because it provides a good ultrasound examination window, which is critical during the necessary ultrasound guidance means to introduce balloons or local treatments or follow-up (e.g. rectal ultrasound for prostate treatment). Furthermore, in the case of side effects such as pain or discomfort or local infection, the balloon can be easily deflated using a thin needle.
In the liquid-inflated configuration, the bladder 12 is preferably constructed of a liquid-impermeable material so that it can maintain its inflated state after filling. Examples of suitable liquids include, but are not limited to, water, saline, and the like.
As noted above, the fluid may include agents useful for imaging, radiation, and/or thermal treatment modalities.
For example, to enhance imaging, the liquid in the capsule 12 may include an imaging contrast agent, such as iodinated or bartated substances or various fluorocarbons for fluoroscopy or CT scanning, echogenic or non-echogenic substances for ultrasound imaging; MRI contrast agents, such as goldolinium, radioisotope species for SPECT or PET scanning. To protect the tissue from radiation, agents such as iodinated substances, baritated substances, fluorocarbons, and the like may be included in the liquid. An agent effective for tissue restoration/repair may also be added to the liquid, in which case the balloon 12 is preferably configured to release such agent into the tissue. It will be appreciated that the above-described agents may be selectively added or incorporated into the material of the capsule 12, in which case they may be released upon degradation of the device 10 or upon absorption of a therapeutic dose (e.g., radiation).
The port 14 may be formed with a plurality of channels to enable fluid circulation with the inflated bladder 12. This liquid circulation enables tissue cooling or heating as necessary. For example, when performing thermal ablation, cooling of non-therapeutic tissue may be achieved by circulation of cold water. It will be appreciated that in this case, the balloon 12 is preferably constructed such that the cooled side (facing the non-treated tissue) is more thermally conductive than the side of the balloon 12 facing the treated tissue.
The port 14 may include other channels that can incorporate viewing devices such as endoscopes or ultrasound sensors that can be used to assess the effect of the treatment, or therapeutic probes such as radiofrequency or high energy ultrasound probes, or optical fibers that can be used for probing or transillumination.
It will be appreciated that various gelling liquids may also be used to inflate the bladder 12. These gelling liquids may be used to enhance the tissue protective qualities of bladder 12 by providing a physical liner that can further protect the removed/separated tissue from physical damage resulting from such removal or separation. Gelling liquids are also advantageous in case of rupture, the gel will remain locally and not dissipate. Examples of gelling fluids that may be used in the expansion device 10 of the present invention include, but are not limited to, absorbable hemostatic agents such as gelatin, cellulose, bovine collagen, and biodegradable synthetic binders such as polyethylene glycol (PEG).
The liquid used to inflate the balloon 12 may also include a fluorophore or any other light transmissive substance that can emit or reflect light for guiding a procedure performed on the tissue being treated. Alternatively, such light reflecting/emitting substances may be incorporated into the material of the capsule 12.
As described herein, the apparatus 10 of the present invention is preferably inserted and positioned within tissue using a guide device.
Thus, according to another aspect of the present invention, a system is provided that may be used for tissue removal or separation.
Such a system comprises a device 10 and guiding means detachably attached to the device 10. The guide means is used to insert and position the device 10 and to expand the balloon 12 when in place.
The guide may be a thin catheter or blunt-tipped needle (cannula) of about 1-5mm in diameter, preferably 2-3mm in diameter. The guiding means has an inner lumen through which the balloon inflation liquid (or rigid element) can be guided from a device such as a syringe (in the case of a liquid) into the balloon 12. Balloon inflation can be monitored by using different imaging techniques, for example: direct viewing, transillumination, fluoroscopy, endoscopic or laparoscopic US, CT scan, MRI, endoscopic viewing, and the like. The guide is preferably constructed of a biomedical grade elastomer such as PVC or polyurethane.
In the event that the device 10 is left in the body, the guide is detached from the device 10, which preferably remains inflated by the self-sealing of the port 14. Such self-sealing may be achieved by a one-way valve incorporated into the port 14, by the viscosity of the balloon inflation liquid (e.g., gel-forming liquid), or by a biodegradable sealing mechanism such as described below with reference to fig. 1 e. A cutting catheter made of biocompatible material and having a sharp edge may be used to separate the device 10 from the guide when necessary.
FIG. 1e illustrates one embodiment of a system for tissue removal or separation, referred to herein as system 100. The system 100 includes the device 10 shown in a collapsed (rolled) state. The system 100 also includes a guide 20 that includes a needle for attachment to the port 14 of the device 10, an encapsulating sleeve 28 for securing the device 10, and an expansion sleeve 26 for securing the encapsulating sleeve 28.
The needle 22 and The dilating cannula 26 are used in a manner similar to known Seldinger techniques (The Seldingertechnique, redeployed by Acta Radiologica in 1953, AJR Am J Roentgenol, 1984 Jan; 142 (1): 5-7). This minimally invasive technique is used to pass a device or substance through a dilating cannula into a specific location in the body. Thus, positioning the dilation sleeve 26 within the body tissue enables the device 10 (rolled or folded within the encapsulation sleeve 28) to be delivered to a particular body location. Once positioned, the device 10 is deployed in the correct position and orientation by retracting the two sleeves and the inflation bladder 12 (e.g., via a syringe connected to the port 34 of the needle 22). The device 10 is then sealed against air leakage by using the one-way valve or self-sealing mechanism described above. Alternatively, the port 14 of the device 10 may be sealed by using a biodegradable plug 30, which plug 30 is forced to penetrate into a non-elastic biodegradable tube 32 that adheres to the sand function of the port 14. Alternatively, sealing may be accomplished by using a resilient compression ring or by knotting the port 14.
When used in a lengthy procedure, the needle 22 of the introducer 20 is detached from the inflated and sealed device 10 and removed from the body, otherwise, after the procedure, the needle 22 with the attached device 10 is removed from the body along with the dilating cannula 26 and the encapsulating cannula 28.
Examples 3-8 of the examples section that follows describe the use of the system 100 in multiple treatment sessions.
Thus, the present invention provides a device and system that can be used to protect tissue from the harmful effects of treatment. As described herein, an important feature of the present device is that it is capable of uniformly removing/separating tissue in a manner that minimizes tissue damage, while being implantable and optionally biodegradable, thereby enabling repeated treatments of a tissue region without the need to repeat the process of positioning within the tissue.
The term "about" as used herein means ± 10%.
Other objects, advantages and novel features of the present invention will become apparent to those skilled in the art upon examination of the following non-limiting examples. Furthermore, each of the various embodiments and aspects of the present invention as described hereinabove and claimed in the claims section below can be supported by the following examples.
Examples of the invention
Reference is now made to the following examples, which together with the above descriptions illustrate the invention in a non limiting manner.
Example 1
Manufacture of bladders
An important feature of the bladder of the present device is its ability to maintain a predetermined shape upon impact. This feature is critical to optimize tissue removal/separation and reduce local tissue pressure. For the same reason, the bladder of the present device is preferably manufactured to have a smooth, seamless outer surface. To meet these demands, a unique production process is designed. This process combines two production concepts: investment casting and dip molding.
Dip molding is used to "build" the walls of the capsule by dipping a preformed mold of the capsule into a solution formed of a polymer dissolved in an organic solvent. The preform mold is made of a material that is subsequently separated from the interior of the capsule through its exit port. Unlike known investment casting processes, wax cannot be used because it is soluble in organic solvents such as alcohols, chlorinated hydrocarbons, alkanones, acetonitrile, dialkyl ethers, cyclic ethers, alkyl acetates, and common aromatic solvents. Typical solvents include butanol, dichloromethane, chloroform, butanone, acetone, acetonitrile, disopropyl ether, tetrahydrofuran, dioxane, ethyl acetate and butyl acetate, and toluene. The only casting agents that can be used are hydrophilic in nature, including proteins, polysaccharides, and various synthetic and semi-synthetic polymers. Examples include, but are not limited to, gelatin, agar, alginate, hydroxypropyl cellulose, poly (acrylic acid-methyl methacrylate), chitosan, dextran, and arabinogalactans.
Alternatively, an alloy having a low melting temperature (e.g., an alloy including a rare earth metal) may be used for the mold. These molds are heated, melted, and separated at a temperature below the melting temperature of the coating polymer.
The shape of the balloon is based on the anatomy of the target site and is designed to achieve optimal separation with minimal local pressure on the surrounding tissue/organ.
The following provides a step-wise description of the capsule production process of the present invention.
(i) A mold of the desired bladder shape is prepared.
(ii) Hot casting agent (10% W/V agar solution) was poured and allowed to wait for 15 minutes to cool the mold and harden.
(iii) The bladder model was separated from the mold and adhered to the dip molded handle (see fig. 2).
(iv) The model is immersed into the dipping solution (e.g., 10% W/V biodegradable polymer in organic solvent) at a constant speed (-20 cm/min).
(v) Step (iv) is repeated a plurality of times (e.g. 6 times) until the desired coating thickness is obtained.
(vi) Wait until the organic solvent evaporates (2-3 hours).
(vii) The casting agent is removed through the mouth of the bag by heating the mold and washing with water.
It will be appreciated that when the balloon is filled with biodegradable fibres, it may alternatively be formed by welding or bonding together two films of balloon material. The film is prepared using a "pressure forming", "film extrusion" or "blown film" process. The film is then welded along the path outside the capsule using precise and controlled ultrasonic energy, or bonded along the bonding path using precisely deposited organic solvents.
Example 2
Prostate cancer
Prostate cancer is the most common malignancy in men, with 220000 new cases diagnosed each year in the united states, and 50000 patients receive radical prostatectomy each year in the united states. During the last few years, there has been an increasing trend towards performing such procedures with minimal invasive techniques, such as laparoscopic radical prostatectomy.
In radical prostatectomy (using either open or laparoscopic methods), the device of the present invention is inserted into the space between the rectum and prostate using a transperineal method guided by transrectal ultrasound (see fig. 3 a). Initially, a thin needle of thickness 22-18 is introduced into the space under transrectal ultrasound guidance, and the virtual space is dilated by injecting 5-22cc of physiological fluid, e.g., 0.9% sterile saline. Inserting a guide wire through the needle into the space; removing the needle and dilating the tract using a dilator; passing an introducer sheath over the dilator and removing the dilator and guidewire; a folding device having a cannula measuring between 2 and 3mm in diameter is guided through the introducer cannula and the balloon is deployed and inflated in the correct direction in the space between the rectum and prostate. Preferably, pear-shaped non-distensible balloons with a length of 3-5cm, a width of 3-5cm and a height of 1-2cm are used (see FIGS. 3 b-c). The thickness of the balloon will be between 10-20mm based on expansion with biodegradable materials or physiological solvents. A specific bladder size will be used that corresponds to the prostate size of a specific patient. Thus, the optical fiber may be introduced into the capsule through the needle and the needle may be removed. During detachment of the prostate from the rectum, the optical fiber is used for illumination, and the expansion space between the rectum and the prostate is observed laparoscopically with translucency. With this method, the boundary of the prostate can be clearly seen, and the prostate can be safely and rapidly separated from the rectum and the erectile nerves existing at the side of the rectum. During this process, the capsule of the device is preferably filled with gel, in which case puncturing of the capsule wall with a surgical instrument or injury caused by thermal energy will not result in losses preventing removal. After the procedure, the balloon and gel are removed using an aspirator and laparoscopic instruments.
In the united states, approximately 100000 patients receive prostate radiation therapy annually. Half of these cases were performed by external beam radiation, and the other half by short-range therapy. During prostate irradiation, the device of the present invention is preferably a pear-shaped capsule that is 3-5cm long, 3-5cm wide, and 1-2cm high when inflated. As mentioned above, under local anesthesia, the pouch is inserted into the correct space between the rectum and prostate. The balloon is then expanded and filled with a physiological fluid or gel to its final size and correct orientation. The catheter is then separated from the expanded balloon, and the balloon is sealed to prevent leakage. Such sealing may be accomplished by using a biodegradable plug as described above or by knotting the biodegradable supply tube. The capsule is sealed during radiation treatment to prevent leakage thereof. The patient received 30-40 courses of radiation at 70-84Gy for the prostate over a period of 5-6 weeks on an ambulatory basis. The capsules and/or gels are therefore selected in such a way as to degrade after this period of time. Furthermore, radiation barriers in the form of iodinated substances or fluorocarbons may be introduced into the pouch and/or gel to further reduce exposure of the rectal wall, erectile nerves and pouch bottom to radiation and thus allow higher radiation doses (e.g. greater than 80Gy or 8000rads) to be used. Alternatively, a radiotracer may be used in order to be able to delineate the prostate during radiotherapy. The bladder and external urinary sphincter can be further protected by using additional spacers at the bottom of the prostate front surface and between the sphincter and the tip of the prostate. Moreover, because these spacers compress the prostate and separate adjacent tissues, the respiratory motion of the prostate is reduced, allowing a more accurate dose to be delivered to the prostate.
The device of the present invention may also be used for prostate cancer cryotherapy. In this case, a transperineal positioning device with thermal insulation and other ports for hot water circulation, or a device with heat conduction means is utilized. In the latter case, the device may incorporate thermally conductive gels or carbon particles, which may be heated by a remote radio frequency source, for example located within the rectal cavity, or by the use of a magnetic field.
Similar devices may be used for thermal ablation treatment of prostate tumors or benign hyperplasia of the prostate. In this case, intermittent or continuous fluid circulation may be used to cool the rectal wall and erectile nerves. Furthermore, when using a spacer balloon, a heat reflective coating applied to the side facing the prostate may be used to reflect the radiated energy reaching the rectum back into the prostate.
Example 3
Gallstone
Prevention of removal may also be performed during laparoscopic cholecystectomy. In the united states, approximately 400000 such cases occur annually, with gallstones being the majority.
In cholecystectomy, the pouch is preferably in the shape of an elongated (5-7 cm long, 3-5cm wide, 1-2cm thick) balloon (see FIGS. 4 b-c). The device is preferably introduced between the gallbladder and the liver in order to separate the organs and facilitate separation (see fig. 4 a).
The balloon is folded in the covering sleeve and connected to the supply catheter, and the device is introduced into the abdominal cavity through a 5mm port. Initially, minimal water separation is performed between the organs to create a space, then the device folded in a covered sleeve is introduced into the space, the sleeve is removed, and the balloon is inflated with a liquid or gel. The catheter is then separated from the inflated balloon and the balloon is sealed to prevent leakage. The catheter separation enables introduction of a surgical instrument through the catheter port and separation of the gallbladder from the liver. The use of a haemostatic agent such as fibrin, thrombin, alginate, gelatin or cyanoacrylate (optionally incorporated into the capsule) enables the bleeding area to reach homeostasis.
Example 4
Large intestine tumor
Tissue removal may also be performed during laparoscopic colectomy. In the united states, approximately 300000 such cases occur annually, with the majority of large bowel tumors.
In a colectomy, an elongated pouch of 10-20cm in length, 3-7cm in width and 1-3cm in thickness (when inflated) is preferably used. The balloon is introduced in its covering sleeve between the right colon and the retroperitoneal cavity, or between the left colon and the retroperitoneal cavity, or between the rectum and the sacrum, or between the rectum and the bladder, in order to separate these tissues and facilitate separation (see fig. 5 a). Initially, a minimum of water separation is performed between the organs to form a space, then the device folded in a covered sleeve is introduced into the space, the sleeve is removed, and the balloon is inflated with a liquid or gel in the correct direction.
The catheter is then separated from the inflated balloon and the balloon is sealed to prevent leakage. Catheter detachment enables introduction of surgical instruments and separation of tumor tissue through the catheter port.
Example 5
Cervical cancer
Cervical cancer is one of the most common tumors in women, with approximately more than 100000 cases per year in the united states. Most of these cases are treated by cavity radiation therapy. During this treatment, the radiation can injure the rectum, bladder and small intestine.
The device of the invention is inserted between the rectum and posterior vaginal wall/cervix under transrectal or transvaginal ultrasound guidance through the posterior vaginal wall or perineum (see fig. 6 a). Extending the pouch to the Douglas pouch or providing additional equipment to elevate the bowel. The folding device and the sleeve, which measure between 2 and 3mm in diameter, are introduced through the guiding sleeve and the balloon is unfolded and inflated in the correct direction in the space formed between the rectum and the vagina/cervix (as described above). The elongated balloon is 3-10cm long and 3-5cm wide and has a variable (inflated) thickness of 1cm in the interrectal vaginal space and 5cm at the distal Douglas cul-de-sac position (see fig. 6 b-e).
The catheter is then separated and the balloon sealed as described above. Radiation therapy is then performed. Patients with cervical squamous cell carcinoma stage IB-IVB (a stage determined by the international federation of obstetrics and gynecology) were treated with a combination of External Beam Radiation Therapy (EBRT) and high dose rate intraluminal short-range therapy (HDR-ICBT). For early patients, 20 grams (Gy) of EBRT was delivered into the entire pelvis, followed by 24Gy (in 4 segments) of HDR-ICBT and 30Gy of center-masked EBRT. For advanced patients, 20-40Gy of global pelvic EBRT was performed, followed by 24Gy (divided into 4 segments) of ICBT and 30-10Gy of center-masked EBRT. The whole treatment course is about 6 weeks.
Example 6
Rectal cancer
Rectal cancer is a common tumor with 145000 new cases per year in the united states alone. In 30-40% of cases, external beam radiation is applied either before or after surgery. Such treatment can result in damage to the bladder, vagina and small intestine.
The device of the present invention is positioned between the bladder and colon or between the rectum and bladder using transrectal, transvaginal ultrasound guidance or CT guidance (see fig. 7a) and extends into the Douglas pouch through the perineum or has additional devices entering into the Douglas pouch through the perineum. The pouch may be extended into the Douglas pouch to elevate the bowel. The folding device and the cannula, which measure diameters between 2 and 3mm, are introduced through the guiding cannula and the balloon prepared as described above is deployed and inflated in the space formed between the rectum and the bladder. An elongated balloon 3-10cm long and 3-5cm wide with variable thickness (when inflated) is used, 1cm thick in the intervesico-rectal space and 5cm high at the distal Douglas fovea (see fig. 7 b-c).
The catheter is then separated and the balloon sealed as described above. Radiation therapy was then administered and the patient received 45Gy (4500rad) delivered in 25 fractions over 5 weeks with or without the addition of neoadjuvant chemotherapy. Surgery is performed 4-6 weeks after completion of the radiation session. Radiotherapy can also be administered in an adjuvant manner after surgery. In the latter case, the prescribed radiation dose is 50.4Gy provided in 28 fractions.
Example 7
Pulmonary tumors and mediastinal lymphomas
The device of the invention may also be used during radiotherapy of a lung tumour or lymphoma located in the mediastinum. In lung tumors, the sac is preferably positioned between the lung and mediastinum, containing the great vessels, heart, spine and spinal cord, and lymphatic vessels and nodules, in order to separate possible internal tumors from healthy tissue. In lymphomas, the device is preferably positioned between the enlarged lymph nodes located in the superior mediastinum and the heart and great vessels, spine and lung tissue. The device is preferably positioned under CT guidance. When inflated, the balloon is preferably 5-10cm long, 3-5cm wide and 1-2cm thick (see FIGS. 8 b-c). Multiple small bladders may also be used to effectively cover the complex space.
The folding device and the cannula, which measure between 2 and 3mm in diameter, are introduced through the guide cannula and the balloon is deployed and expanded in the correct direction in the mediastinal space.
The catheter is then separated and the balloon sealed as described above. In the case of lung tumors, radiation therapy is performed in 45Gy 15 to 70Gy 70 sessions between 3-10 weeks, depending on the tumor type and stage. Such radiation therapy is typically performed in conjunction with chemotherapy. In the case of mediastinal lymphoma, chemotherapy is performed followed by 36Gy dose of concurrent radiation therapy for large mediastinal disease (bulkymedianal disease) within 4-6 weeks.
Example 8
Breast cancer
Another application may be radiation therapy for breast cancer. This tumor is the most common tumor in women, with 300000 new cases each year in the united states. Most patients receive lumpectomy. In most cases, adjacent breast tissue is irradiated and tumor cases located near the breast wall, chest wall and lungs receive significant doses of irradiation.
The folding device and cannula, which measure between 2 and 5mm in diameter, are introduced through the guiding cannula and the balloon is deployed and expanded in the space between the breast and the abdominal wall (see fig. 9 a). Preferably, circular flattened bags with a diameter of 5-15cm and a thickness of 1-3cm are used in the process (see FIGS. 9 b-c).
The catheter is then separated and the balloon sealed as described above. Radiation therapy is then performed. The standard Radiation Therapy (RT) technique following Breast Conservation Surgery (BCS) is to treat the entire breast up to a total dose of 45-50Gy with or without tumor bed enhancement, with a typical treatment comprising 30 courses over six weeks.
It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-set.
While the present invention has been described in conjunction with specific embodiments, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents, and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.