Patent Application
20210251677
The present invention relates to treating the prostate.
All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each such individual publication or patent application were specifically and individually indicated to be so incorporated by reference.
The present invention relates to the field of treating benign prostatic hyperplasia and other prostate disease.
Benign prostatic hyperplasia (BPH) arises when the stromal and epithelial cells of the prostate become enlarged. The side effects from this hyperplasia result in the impingement of the urethra. A common method of treatment for benign prostatic hyperplasia (BPH) is transurethral resection of the prostate (TURP) which is the gold standard for surgical treatment. This approach has its disadvantages. The patient often has two recovery days in the hospital and needs to undergo general anesthesia for the operation. There is a need for a minimally invasive treatment of BPH and other prostate diseases, such as cancer.
Disclosed herein are embodiments of a transurethral cryotherapy (TC) system and methods of its use. The TC system has several advantages over the gold standard. Since the cryotherapy is less traumatic, the procedure may be performed in an out-patient, or office, setting allowing the patient to go home on the same day. The procedure may also be performed without general anesthesia.
In one embodiment of a transurethral cryotherapy system, the apparatus may generally comprise a catheter which is sized for placement within a body lumen, at least one balloon positioned along a length of the catheter and defining a contact region for thermally contacting a portion of the body lumen which is in proximity to tissue to be treated, and a reservoir in fluid communication with the at least one balloon through at least one lumen defined through the length of the catheter. The at least one balloon may be configured to receive a refrigerant from the reservoir introduced through the at least one lumen until the contact region is at least partially expanded, the catheter being adjustable to selectively align the contact region against the portion of the body lumen to preferentially cool the portion relative to a remainder of the body lumen surrounding the portion.
In another embodiment for a method of applying a cryotherapy treatment, the method may generally comprise advancing a catheter within a body lumen such that at least one balloon positioned along a length of the catheter is placed near or at a portion of the body lumen which is in proximity to tissue to be treated, adjusting a position of the catheter to align a contact region defined along the at least one balloon into contact against the portion of the body lumen, initiating a refrigerant to flow through at least one lumen defined through the length of the catheter and into the at least one balloon such that the contact region is at least partially expanded into thermal contact against the portion of the body lumen, and applying the refrigerant through the contact region until the tissue to be treated is preferentially cooled through the portion of the body lumen relative to a remainder of the body lumen surrounding the portion.
The TC catheter may also have a urine drainage lumen to allow urine to drain from the bladder through the catheter, similar to a Foley catheter. The TC catheter may be sized similar to a Foley catheter, or around 16 French.
Cryotherapy may be administered using a cooling fluid, or cryogen, such as Nitrogen, Nitrogen Oxide, Carbon Dioxide, argon, air, or any other suitable cryogens. The coolant may be delivered to a substance, such as a metal such as copper, to cool the substance which in turn cools the tissue, either directly or through an intermediate zone of fluid, liquid, gas, air and/or tissue. Alternatively, the cryogen may be sprayed, vaporized, or administered from openings in the shaft of the TC catheter, directly to the tissue or to an intermediate zone near the tissue. The TC catheter is designed such that only a specific section, the cryotherapy section, delivers the cryotherapy. This protects the tissue that does not require treatment. The cryotherapy section is generally aligned with the prostate to help deliver therapy.
Temperature sensors may be placed at, near or distanced from the cryotherapy section of the TC catheter to determine the temperature of the treatment, the treated tissue, the nearby tissue and/or the untreated tissue. This temperature data may be used by a controller to control the treatment temperature to allow proper treatment, while minimizing damage to nearby tissue.
The cryo-affected zone may be controlled, both in size and shape, by the configuration of the cryotherapy section of the TC catheter. Several embodiments are included here to achieve different cryo-affected zone shapes/sizes.
The embodiment of the TC catheter system shown in
This embodiment uses a cryogen fluid, such as a cryogen gas, circulating within cryotherapy balloon 1402 to cause apoptosis or necrosis of targeted prostate tissue/cells. An example of a cryogen gas is argon gas. Other gases, such as air, may be used. Possible coolants/cryogens are listed in the table below:
In some embodiments, the coolant is a refrigerant, or a coolant that cools to a less cold temperature and may evaporate at atmospheric pressure, and be liquefied at a lower pressure, for example, coolants with a boiling point above −180° C. For example, refrigerants in the R400 series (naming developed by DuPont® Corporation), which are generally zeotropic blends, may be used. For example, R410A may be used.
Cryotherapy balloon 1402 may have a radius of about 1.0 cm and a length of about 4.0 cm when inflated.
The cryogen may be introduced via cryogen inflow lumen 2002 and exit through a different cryogen exit lumen, or, the cryogen may enter and exit via the same lumen. In embodiments where the cryogen enter and exit a balloon via the same lumen, the cryogen may be introduced, and then actively removed by the controller at a preset time since introduction, or at a preset temperature since introduction. Alternatively, the cryogen may exit the lumen naturally when the pressure exceeds a cryogen exit pressure. This exit may be controlled by an active or passive valve.
The sheath may be positioned onto the catheter before the procedure, depending on the anatomy. Different types of sheaths may be used depending on the prostate treatment area and area that is to be protected. In some embodiments, the sheath may be repositioned or replaced during the procedure. For example, in some embodiments the sheath may be connected to an elongated guide (not shown) that extends all or most of the length of the catheter so that the physician can move the sheath while the catheter is in place in the prostate.
Sheath 3202 may be made from a polymer, metal, silicone, or other suitable material.
Some embodiments of the sheath have markings or areas which are visible under visualization, such as ultrasound, so that the physician can identify the position of the openings of the sheath with respect to the prostate while it is in position. This allows the physician to target the therapy at the areas which need it while protecting the areas of the prostate that do not require therapy.
Some embodiments of the TC system may include a relatively compliant cryotherapy balloon. Some embodiments of the TC system may include a relatively non-compliant cryotherapy balloon. The sheaths used with relatively non-compliant balloons may require larger openings than those used with relatively compliant balloons, to allow enough of the balloon to protrude and effectively treat the prostate.
Although most embodiments disclosed herein refer to a system designed to treat the prostate, it is understood that many of the embodiments may be used for other applications. For example, any of the treatment, or balloon orienting embodiments may be used for applying temperature, pressure or other directed treatments to blood vessels or other organs. For example, embodiments with balloon restricting sheaths, such as those shown in
The embodiment in
Some embodiments of the TC System effectively debulk the prostate gland by causing cell apoptosis, which substantially avoids the side effects and inflammation of cell necrosis. This is done via the localized delivery of sublethal temperature cryogen. Cryogen temperatures may be 0 to −20° C. or alternatively, 0 to −40° C. or alternatively, 0 to −50° C. or alternatively, −10 to −20° C. or alternatively, −20 to −40° C. or alternatively, −20 to −50° C. More than one temperature may be used over time to affect the cells. Adipose cells exposed to these temperatures undergo apoptotic mediated cell death and are subsequently cleared by macrophages to reduce localized fat tissue. This treatment modality is advantageous in that apoptosis, or programmed cell death, does not induce a host immune response, therefore reducing the risk of chronic inflammation. Sublethal cryotherapy may also limit peripheral damage, preventing damage to peripheral nerves in the penis essential for the preservation of sexual function.
Embodiments of the TC catheter/system disclosed herein allow for uniform cryothermic delivery to both lateral lobes of the prostate through a single transurethral approach. The TC catheter may utilizes a low durometer polyurethane medical balloon inflated with a cryogen to widen the urethral lumen and deliver a uniform cryothermic dose to the prostate. By optimizing the balloon dimensions, balloon pressure, duration of cryotherapy administered, and the rate of cooling, the TC system can provide cryothermic dosing to the entire prostate through a single transurethral approach without the need for repositioning.
The temperature applied to the prostate may vary over time. For example, the TC system may first expose the prostate to a colder temperature, to cool the tissue quickly, then switch to a slightly less cold temperature, so that cell necrosis is limited. For example, the TC system may expose the prostate to a temperature around −50° C. for a period of time, then adjust the applied temperature to around −20° C. for a period of time to cause cell apoptosis. In some embodiments, the target temperature of the majority of the prostate cells is about −15° C. In some embodiments, the temperature of the majority of the prostate cells does not drop below (colder than) −20° C.
In some embodiments, the prostate cells are maintained at a temperature of about −10° C. to about −20° C. for a period of 30-60 minutes. In some embodiments, the prostate cells are maintained at a temperature of about −15° C. to about −20° C. for a period of 30-60 minutes. In some embodiments, the prostate cells are maintained at a temperature of about −10° C. to about −20° C. for a period of 0-30 minutes. In some embodiments, the prostate cells are maintained at a temperature of about −15° C. to about −20° C. for a period of 0-30 minutes. In some embodiments, the prostate cells are maintained at a temperature of about −10° C. to about −20° C. for a period of 60-120 minutes. In some embodiments, the prostate cells are maintained at a temperature of about −15° C. to about −20° C. for a period of 60-120 minutes.
Some embodiments of the TC system may cycle the temperature of device through higher and lower temperatures once or repeatedly over time.
Some embodiments of the TC system may follow the cooling period with a warming period, by infusing warm fluid, such as water, into the balloon or into the catheter. The timing and temperature of the cooling and/or warming periods may be precisely controlled so that the tissue exposure to cold is tightly controlled. The control of the cooling and/or warming periods' temperature and/or time may be controlled manually, or may be controlled automatically or may be controlled via a feedback mechanism, such as temperature sensors in the system.
Embodiments disclosed herein may or may not include a drainage or urine lumen.
Variables that are controlled for the cryotherapy include: min temperature (degrees C.), min temperature hold time (seconds), cooling rate (degrees C./second), thawing rate (degrees C./second), pressure, etc. The treatment can involve one cooling cycle or multiple cooling cycles. Min temperature can range from about 25C to about −40C. Alternatively, Min temperature can range from about 10C to about −10C. Alternatively the range can be between about 0C to about −20C. Hold time for a given cycle can range from about 5 seconds to about 60 minutes. Cooling and heating rates can range from about 1C/minute to about 500C/minute.
In some embodiments that use a coolant, the coolant may be cycled through a balloon while the balloon is positioned within the urethra in proximity to the prostate. The coolant may be introduced into a balloon, and after a period of time, vacuumed out using a pump or similar in communication with the controller. This vacuuming may be automatically performed by the controller or performed manually. There may be more than one cycle of introducing and removing coolant from a balloon during a procedure. Alternatively, a balloon may have more than one entry point so that the coolant can by cycled through either in boluses, or continually or semi-continually.
Cryotherapy has advantages over radio frequency or microwave ablation technologies. These technologies rely on electromagnetic radiation to excite tissues and elevate their temperature and cause an ablation. Polar molecules, such as water, are particularly excited by electromagnetic radiation such as microwaves. Stromal and epithelial tissue has little water content compared to muscle tissue and therefore it is more challenging to ablate fatty tissues with electromagnetic radiation. Since cryoablation causes apoptosis through thermal shock or modification, it is less sensitive to water content in tissues and can have a meaningful and controllable impact on fatty tissues.
Post procedure the stromal and epithelial cells will be ablated and slowly removed and reduced in size by the body, reducing impingement of the urethra. Benefits include increased urinary flow rates, frequency of nocturia, frequency of bladder emptying and post void urine residual.
The energy to heat the heating elements of the TC catheter and/or to cool the cooling elements of the TC catheter are supplied by an energy applicator which may be part of the controller. The controller may also include temperature sensing elements, temperature control system, balloon pressure sensing elements, etc.
Some embodiments of the transurethral cryotherapy system for treatment of benign prostatic hyperplasia include an energy applicator for applying a cooling temperature to urethra tissue adjacent to the applicator and to prostate tissue which surrounds the urethra tissue and extends radially outwardly therefrom; and a temperature control system for sensing the temperature of the urethra tissue and decreasing the cooling temperature applied by the applicator based on the sensed temperature so that the urethra tissue temperature decreases in increments, wherein the temperature control system includes a temperature sensor disposed near the urethra tissue for sensing the temperature of the urethra tissue and producing a temperature output signal indicative of the temperature, a controller coupled to the temperature sensor, receiving the temperature output signal, and producing a programmed temperature control signal in response to the temperature output signal, and a cooling temperature source coupled to the controller, receiving the temperature control signal, and regulating the energy applied by the applicator based on the temperature control signal such that the applicator simultaneously maintains the urethra tissue at a set temperature for a set amount of time required for treatment of benign prostatic hyperplasia.
Example of Data Processing System
As shown in
Typically, the input/output devices 4110 are coupled to the system through input/output controllers 4109. The volatile RAM 4105 is typically implemented as dynamic RAM (DRAM) which requires power continuously in order to refresh or maintain the data in the memory. The non-volatile memory 4106 is typically a magnetic hard drive, a magnetic optical drive, an optical drive, or a DVD RAM or other type of memory system which maintains data even after power is removed from the system. Typically, the non-volatile memory will also be a random access memory, although this is not required.
While
Some portions of the preceding detailed descriptions have been presented in terms of algorithms and symbolic representations of operations on data bits within a computer memory. These algorithmic descriptions and representations are the ways used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art. An algorithm is here, and generally, conceived to be a self-consistent sequence of operations leading to a desired result. The operations are those requiring physical manipulations of physical quantities.
It should be borne in mind, however, that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities. Unless specifically stated otherwise as apparent from the above discussion, it is appreciated that throughout the description, discussions utilizing terms such as those set forth in the claims below, refer to the action and processes of a computer system, or similar electronic computing device, that manipulates and transforms data represented as physical (electronic) quantities within the computer system's registers and memories into other data similarly represented as physical quantities within the computer system memories or registers or other such information storage, transmission or display devices.
The techniques shown in the figures can be implemented using code and data stored and executed on one or more electronic devices. Such electronic devices store and communicate (internally and/or with other electronic devices over a network) code and data using computer-readable media, such as non-transitory computer-readable storage media (e.g., magnetic disks; optical disks; random access memory; read only memory; flash memory devices; phase-change memory) and transitory computer-readable transmission media (e.g., electrical, optical, acoustical or other form of propagated signals—such as carrier waves, infrared signals, digital signals).
The processes or methods depicted in the preceding figures may be performed by processing logic that comprises hardware (e.g. circuitry, dedicated logic, etc.), firmware, software (e.g., embodied on a non-transitory computer readable medium), or a combination of both. Although the processes or methods are described above in terms of some sequential operations, it should be appreciated that some of the operations described may be performed in a different order. Moreover, some operations may be performed in parallel rather than sequentially.
Embodiments of the systems and/or devices and/or methods enclosed herein may be used for other clinical applications also, including treating the sinuses, the esophogus, the intestines, the gall bladder, etc.
This application is a continuation of International Patent Application No. PCT/US2019/058897 filed Oct. 30, 2019, which claims the benefit of priority to U.S. Provisional Application No. 62/754,400 filed Nov. 1, 2018, U.S. Provisional Application No. 62/832,705 filed Apr. 11, 2019, and U.S. Provisional Application No. 62/874,446 filed Jul. 15, 2019, each of which is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 62754400 | Nov 2018 | US | |
| 62832705 | Apr 2019 | US | |
| 62874446 | Jul 2019 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/US2019/058897 | Oct 2019 | US |
| Child | 17240780 | US |
