阅读说明：本技术 用于压迫肿瘤的装置和方法 (Device and method for compression of tumors ) 是由 M·G·塔尔 G·玛格纳齐 O·赫恩 于 2019-08-13 设计创作，主要内容包括：一种设备(500),其用于压迫受试者身体的器官中的肿瘤以用于增加肿瘤内的压力,直到在肿瘤中引起局部缺血和/或坏死为止。该设备包括长形本体(501),该长形本体用于经由在身体中形成的外科通路到达器官的表面。该设备包括收紧机构(502),该收紧机构用于围绕器官和/或肿瘤的体积部分收紧张力构件。收紧机构包括牵拉构件(504、505)和力操纵器单元(513),该力操纵器单元用于经由牵拉构件施加张紧力以迫使张力构件进入收紧状态。该设备包括固定机构(503),该固定机构用于固定张力构件的第一部分和第二部分,以用于使张力构件维持处于收紧状态。(A device (500) for compressing a tumor in an organ of a subject's body for increasing pressure within the tumor until ischemia and/or necrosis is caused in the tumor. The apparatus includes an elongated body (501) for accessing a surface of an organ via a surgical pathway formed in the body. The apparatus includes a tightening mechanism (502) for tightening the tension member around a volumetric portion of the organ and/or tumor. The tightening mechanism comprises pulling members (504, 505) and a force manipulator unit (513) for applying a tensioning force via the pulling members to force the tensioning members into a tightened state. The apparatus includes a securing mechanism (503) for securing the first and second portions of the tension member for maintaining the tension member in a tightened state.)

1. An apparatus for compressing a tumor in an organ of a body of a subject, the apparatus comprising:

an elongate body configured for accessing a surface of the organ proximate the tumor via a surgical pathway formed in the body of the subject;

a tightening mechanism for tightening a tension member extending around a volumetric portion of the tumor, wherein a first portion of the tension member protrudes from an entrance opening at the surface of the organ and a second portion of the tension member protrudes from an exit opening at the surface of the organ, the tightening mechanism comprising: a first puller member configured for anchoring to the first portion of the tension member; and a force manipulator unit configured for applying a tensioning force via the first puller member to force the tensioning member into a contracted state sufficient to compress the volume portion and/or increase pressure within the tumor; and

a securing mechanism configured for securing the first portion of the tensioning member to the second portion via the elongate body proximate the surface of the organ for maintaining the tensioning member in the tightened state, including after the tightening mechanism has been disengaged from the tensioning member.

2. The apparatus according to claim 1, further comprising a measurement unit configured for indicating a magnitude related to the tensioning force, a change in compression of the volume portion and/or a change in pressure within the tumor when the tensioning member is tightened by the tightening mechanism.

3. The apparatus of claim 1 or 2, wherein the first pulling member is configured to anchor and pull the tension member configured as a flexible wire or strip.

4. The apparatus of any of the preceding claims, wherein the tension member comprises at least one of an implant-grade metal alloy, an implant-grade polymer, an implant-grade textile, and a biodegradable material.

5. The apparatus according to any one of the preceding claims, wherein the tightening mechanism is configured to limit the force manipulator unit to apply the tightening force from the range of 25N to 100N.

6. The apparatus according to any one of the preceding claims, wherein the tightening mechanism is configured for applying the force manipulator unit to automatically increase the tension force to the tension member gradually, continuously or discretely until a selected tension force is reached.

7. The apparatus of any of the preceding claims, wherein the tightening mechanism is configured to limit manual use to a gradual, continuous, or discrete increase in the tension force until a selected tension force is reached.

8. The apparatus of any of the preceding claims, wherein the securing mechanism is configured for applying a fastener to secure the first portion of the tension member to the second portion for an extended period of time sufficient to cause ischemia and/or necrosis in most or all tissue of the tumor when the volume portion is continuously compressed and/or the tumor is forced to increase pressure therein by the tension member during this period.

9. The apparatus of any of claims 1-7, wherein the securing mechanism is configured to couple a fastener to the first and second portions of the tension member to maintain the tension member in the tightened state.

10. The apparatus of claim 9, wherein the fastener comprises a ductile material, and wherein the securing mechanism is configured to crimp the fastener around the first and second portions of the tension member.

11. The apparatus of claim 9 or 10, wherein the fastener includes a tubular fastener body sized to allow the tension member to pass therethrough, wherein the securing mechanism, when applied to crimp the fastener, is configured to compress and/or bend a portion of the fastener body, thereby securing the first and second portions of the tension member to the portion of the fastener body.

12. The apparatus of claim 11, wherein the elongate body comprises a barrel and an anvil disposed at a distal end of the barrel, and the securing mechanism comprises a hammer head slidable in the barrel along a longitudinal axis of the barrel, wherein the securing mechanism is configured to force the hammer head to press the portion of the fastener body against the anvil for compressing and/or bending the portion of the fastener body when crimping the fastener.

13. The apparatus of claim 12, wherein the anvil includes an anvil lumen sized to receive the fastener body therein.

14. The apparatus of claim 13, wherein a longitudinal axis of the anvil lumen is angled relative to the longitudinal axis of the barrel.

15. The apparatus of claim 13 or 14, wherein the securing mechanism comprises a positioning spring configured to force the hammer head into a nominal position such that the hammer head protrudes into the anvil lumen in the absence of the fastener body in the anvil lumen, and is configured to retract when the fastener body is fully received in the anvil lumen.

16. The apparatus of claim 15, wherein the positioning spring is forced to preload under a preload force sufficient to effect anchoring of the fastener body to the anvil when the fastener body is fully received in the anvil lumen.

17. The apparatus of any one of claims 12 to 16, wherein the securing mechanism comprises a retraction spring configured to force retraction and disengagement of the hammer head from the compressed and/or curved portion of the fastener body at the end of, or immediately after, crimping the fastener.

18. The apparatus of any one of the preceding claims, wherein the securing mechanism is functionally independent of the tightening mechanism.

19. The apparatus of any one of the preceding claims, wherein, when the force manipulator unit is continuously or repeatedly applied to tighten the tension member until a selected tension is reached, the tightening mechanism is configured to sequentially perform the following steps:

pulling the first and second portions of the tension member reciprocally from a relaxed state until one of the first and second portions of the tension member reaches a taut state,

pulling the other of the first and second portions of the tension member to the taut state, an

Reciprocally pulling the first and second portions of the tension member from the taut state until a selected tension is reached in the tension member.

20. The apparatus of any of the preceding claims, wherein the second portion of the tension member is fixed relative to the first puller member.

21. The apparatus according to any one of the preceding claims, wherein the tightening mechanism comprises a second pull member configured to be anchored to the second portion of the tension member, wherein the force manipulator unit is configured for applying a tensioning force via the second pull member to force the tension member into a tightened state between the first pull member and the second pull member.

22. The apparatus of claim 21, wherein the first and second puller members are functionally and/or structurally independent of each other in at least one of rotational speed and pulling force.

23. The apparatus of claim 21 or 22, wherein the tightening mechanism includes a tension transfer gear configured to reciprocally transfer force from the force manipulator unit to the first and second pull members.

24. The apparatus of claim 23, wherein a differential gear rotatable with the tension transfer gear reciprocally engages a first pull gear fixedly connected to the first pull member and a second pull gear fixedly connected to the second pull member, wherein rotation of the tension transfer gear transfers the transferred force to rotate the first and second pull gears and equally distribute between the first and second pull gears through the differential gear while permitting differential relative rotation between the first and second pull gears.

25. The apparatus of any one of the preceding claims, wherein the force manipulator unit is selectively connectable to a power source via a computerized controller.

26. The apparatus according to any one of the preceding claims, wherein the force manipulator unit is manually operable by pressing a trigger, wherein the tightening mechanism is configured for incrementally increasing the tightening force to the tension member during at least one cycle of the pressing motion of the trigger and for maintaining the tightening force when the trigger is withdrawn after each of the at least one cycle of the pressing motion.

27. The apparatus of claim 26, wherein the tightening mechanism includes a tension force transfer gear configured to transfer force from the force manipulator unit to the first pull member.

28. The apparatus according to claim 27, wherein the force manipulator unit is connectable to the tension transfer gear by a clutch member selectively switchable between engagement and disengagement with the tension transfer gear.

29. The apparatus of claim 28, wherein the trigger has a first range of motion when the clutch member is engaged with the tension transfer gear and a second range of motion when the clutch member is disengaged from the tension transfer gear, the second range of motion being greater than the first range of motion, wherein the force manipulator unit is prevented from transmitting force to the securing mechanism when the trigger is depressed to an entire range of the first range of motion and is configured to transmit force to the securing mechanism when the trigger is depressed to an entire range of the second range of motion.

30. The apparatus of claim 28, wherein when the clutch member is disengaged from the tension transfer gear, the clutch member is configured for switching into engagement with a stationary force transfer gear, thereby facilitating force transfer from the force manipulator unit for operating the stationary mechanism.

31. The apparatus of claim 30, wherein the clutch member is connected to a selector switch configured to facilitate selective manual switching of the clutch member between: engaging the tightening force transmitting gear after disengaging from the fixed force transmitting gear; and engaging with the fixed force transmission gear after disengaging from the tightening force transmission gear.

32. The apparatus of claim 31, wherein the selector switch is further configured to control a range of motion of a trigger for manually operating the force manipulator, wherein a first range of motion limited by the selector switch when the clutch member is engaged with the stationary force transfer gear is greater than a second range of motion limited by the selector switch when the clutch member is engaged with the tightening force transfer gear.

33. A method for compressing a tumor in an organ of a body of a subject, the method comprising:

inserting an elongated body through a surgical pathway formed in the body of the subject until reaching a surface of the organ proximate the tumor;

tightening a tension member extending around a volumetric portion of the tumor using a tightening mechanism, wherein a first portion of the tension member protrudes from an entrance opening at the surface of the organ and a second portion of the tension member protrudes from an exit opening at the surface of the organ, the tightening comprising:

anchoring the first portion of the tension member to a first puller member, an

Applying tension via the first puller member by a force manipulator to force the tension member into a tightened state sufficient to compress the volume portion and/or increase pressure within the tumor; and

securing the first portion of the tensioning member to the second portion via the elongate body proximate the surface of the organ using a securing mechanism for maintaining the tensioning member in the tightened state, including after the tightening mechanism has been disengaged from the tensioning member.

34. The method of claim 33, further comprising: measuring a magnitude related to the tensioning force, a change in compression of the volume portion, and/or a change in pressure within the tumor when the tensioning member is tightened by the tightening mechanism.

35. The method of claim 33, wherein the securing comprises: applying a fastener to secure the first portion of the tension member to the second portion for an extended period of time sufficient to cause ischemia and/or necrosis in most or all tissue of the tumor when the volume portion is continuously compressed and/or the tumor is forced to increase pressure therein by the tension member during this period.

Technical Field

The present disclosure relates to devices and methods for influencing blood supply to a target tissue within the body of a subject, and more particularly, but not exclusively, to devices and methods (e.g., minimally invasive devices and methods) for inhibiting a tumor, such as a uterine fibroid, by causing ischemia and/or necrosis thereof.

Background

Uterine fibroids (also known as "myomas") are benign tumors that are fed by the uterine arteries and grow within the muscle tissue of the uterus. Fibroids are solid fibrous tissue that grow as individual nodules or clumps, and may range in size from about 1 mm to greater than 20 cm in diameter. Myomas are the most commonly diagnosed tumors in the female pelvis and the most common cause of women undergoing hysterectomy. Common symptoms of myoma include heavy menstrual bleeding, extended menstrual periods, pelvic pressure or pain, and Lower Urinary Tract Symptoms (LUTS).

Fig. 1 illustrates an exemplary uterus having three types of fibroids. Uterine fibroids are classified according to their location relative to the uterus, which affects the symptoms that uterine fibroids may cause and how uterine fibroids may be treated. Fibroids inside the uterine cavity (submucosal or submucosal fibroids) often cause intermenstrual bleeding and severe cramping. Some submucosal fibroids are partially submerged in the uterine cavity and partially submerged in the uterine wall. They also cause large menstrual bleeding (menorrhagia) and intermenstrual bleeding, and are more difficult to remove in hysteroscopy. Intramural fibroids grow in the uterine wall and can range in size from tiny to larger than grapefruit. Many interfural fibroids are not considered to pose a risk to the health of the patient until they reach a certain size. Subserous fibroids are found on the outer wall of the uterus and can even be connected to the uterus by the stem (pedicle fibroids). Known devices, systems and methods for treating uterine fibroids have various limitations and disadvantages.

Disclosure of Invention

The present disclosure relates to devices and methods for influencing blood supply to a target tissue within the body of a subject, and more particularly, but not exclusively, to devices and methods (e.g., minimally invasive devices and methods) for inhibiting a tumor, such as a uterine fibroid, by causing ischemia and/or necrosis thereof.

In certain embodiments, a device for compressing a tumor in an organ of a body of a subject is provided. The apparatus may include: an elongate body configured for accessing a surface of an organ proximate a tumor via a surgical pathway formed in a body of a subject; a tightening mechanism for tightening a tension member extending around a volumetric portion of a tumor, wherein a first portion of the tension member protrudes from an inlet opening at a surface of an organ and a second portion of the tension member protrudes from an outlet opening at the surface of the organ, the tightening mechanism comprising: a first puller member configured for anchoring to a first portion of the tension member; and a force manipulator unit configured for applying a tensioning force via the first puller member to force the tensioning member into a tightened state sufficient to compress the volume portion and/or increase pressure within the tumor; and a securing mechanism configured for securing the first portion of the tension member to the second portion via the elongated body proximate a surface of the organ for maintaining the tension member in a tightened state, including after the tightening mechanism has been disengaged from the tension member.

In some embodiments, the apparatus further comprises a measurement unit configured for indicating a magnitude related to the tension force, a change in compression of the volume portion and/or a change in pressure within the tumor when the tension member is tightened by the tightening mechanism.

In some embodiments, the first pulling member is configured to anchor and pull a tension member configured as a flexible wire or strip.

In some embodiments, the tension member comprises at least one of an implant grade metal alloy, an implant grade polymer, an implant grade textile, and a biodegradable material.

In some embodiments, the tightening mechanism is configured to limit the force manipulator unit to apply a tension force from the range of 25N to 100N.

In some embodiments, the tightening mechanism is configured to apply the force manipulator unit to automatically increase the tension force to the tension member gradually, continuously, or discretely until a selected tension force is reached.

In some embodiments, the tightening mechanism is configured to limit manual use to a gradual, continuous, or discrete increase in the tightening force until a selected tightening force is reached.

In some embodiments, the securing mechanism is configured for applying the fastener to secure the first portion of the tensioning member to the second portion for an extended period of time sufficient to cause ischemia and/or necrosis in most or all tissue of the tumor when the volume portion is continuously compressed and/or the tumor is forced to increase pressure therein by the tensioning member during the period of time. Optionally, additionally or alternatively, the securing mechanism is configured to couple the fastener to the first and second portions of the tension member to maintain the tension member in a tightened state. In some embodiments, the fastener comprises a ductile material, and wherein the securing mechanism is configured to crimp the fastener around the first and second portions of the tension member.

In some embodiments, the fastener includes a tubular fastener body sized to allow the tension member to pass therethrough, wherein, when applied to crimp the fastener, the securing mechanism is configured to compress and/or bend a portion of the fastener body, thereby securing the first and second portions of the tension member to the portion of the fastener body. In some embodiments, the elongate body comprises a barrel and an anvil disposed at a distal end of the barrel, and the securing mechanism comprises a hammer head slidable in the barrel along a longitudinal axis of the barrel, wherein the securing mechanism is configured to force the hammer head to press the portion of the fastener body against the anvil for compressing and/or bending the portion of the fastener body when crimping the fastener. In some embodiments, the anvil includes an anvil lumen sized to receive the fastener body therein. In some embodiments, the longitudinal axis of the anvil lumen is angled relative to the longitudinal axis of the barrel.

In some embodiments, the securing mechanism includes a positioning spring configured to force the hammer head into a nominal position such that the hammer head protrudes into the anvil lumen in the absence of the fastener body in the anvil lumen, and is configured to retract when the fastener body is fully received in the anvil lumen. In some embodiments, the positioning spring is forced to preload under a preload force sufficient to effect anchoring of the fastener body to the anvil when the fastener body is fully received in the anvil lumen.

In some embodiments, the securing mechanism includes a retraction spring configured to force the ram to retract and disengage from the compressed and/or curved portion of the fastener body at the end of or immediately after crimping the fastener.

In some embodiments, the securing mechanism is functionally independent of the tightening mechanism.

In some embodiments, when the force manipulator unit is continuously or repeatedly applied to tighten the tension member until the selected tension is reached, the tightening mechanism is configured to sequentially perform the following steps: pulling the first and second portions of the tension member reciprocally from a relaxed state until one of the first and second portions of the tension member reaches a taut state; pulling the other of the first and second portions of the tension member into a taut state; and reciprocally pulling the first and second portions of the tension member from a taut state until a selected tension is reached in the tension member.

In some embodiments, the second portion of the tension member is fixed relative to the first puller member.

In some embodiments, the tensioning mechanism includes a second puller member configured to be anchored to a second portion of the tension member, wherein the force manipulator unit is configured to apply tension via the second puller member to force the tension member into a tightened state between the first puller member and the second puller member. In some embodiments, the first pulling member and the second pulling member are functionally and/or structurally independent of each other in at least one of rotational speed and pulling force.

In some embodiments, the tightening mechanism includes a tension force transmitting gear configured to reciprocally transmit force from the force manipulator unit to the first and second pull members.

In some embodiments, a differential gear rotatable with the tension transfer gear reciprocally engages a first pull gear fixedly connected to a first pull member and a second pull gear fixedly connected to a second pull member, wherein rotation of the tension transfer gear transfers a transferred force to rotate the first and second pull gears and equally distribute therebetween through the differential gear while permitting differential relative rotation between the first and second pull gears.

In some embodiments, the force manipulator unit is selectively connectable to the power source via a computerized controller.

In some embodiments, the force manipulator unit is manually operable by depressing the trigger, wherein the tightening mechanism is configured for incrementally increasing the tension force to the tension member during at least one cycle of the depressing motion of the trigger and for maintaining the tension force when the trigger is withdrawn after each of the at least one cycle of the depressing motion. In some embodiments, the tightening mechanism includes a tension force transmitting gear configured to transmit force from the force manipulator unit to the first puller member. In some embodiments, the force manipulator unit may be connected to the tension transmitting gear by a clutch member that is selectively switchable between engagement and disengagement with the tension transmitting gear.

In some embodiments, the trigger has a first range of motion when the clutch member is engaged with the tension transfer gear and a second range of motion when the clutch member is disengaged from the tension transfer gear, the second range of motion being greater than the first range of motion, wherein the force manipulator unit is prevented from transmitting force to the securing mechanism when the trigger is depressed to an entire range of the first range of motion and the force manipulator unit is configured to transmit force to the securing mechanism when the trigger is depressed to an entire range of the second range of motion.

In some embodiments, the clutch member is configured for switching into engagement with the fixation force transmission gear when the clutch member is disengaged from the tension transmission gear, thereby facilitating force transmission from the force manipulator unit for operating the fixation mechanism. In some embodiments, the clutch member is connected to a selector switch configured to facilitate selective manual shifting of the clutch member between: engaging the tightening-force transmitting gear after disengaging from the fixed-force transmitting gear; and engaging with the fixed force transmission gear after disengaging from the tightening force transmission gear. In some embodiments, the selector switch is further configured to control a range of motion of a trigger for manually operating the force manipulator, wherein a first range of motion limited by the selector switch when the clutch member is engaged with the stationary force transmitting gear is greater than a second range of motion limited by the selector switch when the clutch member is engaged with the tightening force transmitting gear.

In certain embodiments, a method for compressing a tumor in an organ of a subject's body is provided. The method can comprise the following steps: inserting the elongate body through a surgical pathway formed in the body of the subject until reaching a surface of an organ proximate the tumor; tightening, using a tightening mechanism, a tension member extending around a volumetric portion of the tumor, wherein a first portion of the tension member protrudes from an inlet opening at a surface of the organ and a second portion of the tension member protrudes from an outlet opening at the surface of the organ, the tightening comprising: anchoring a first portion of the tension member to the first puller member; and applying tension via the first puller member by the force manipulator to force the tension member into a tightened state sufficient to compress the volume portion and/or increase pressure within the tumor; and securing the first portion of the tensioning member to the second portion via the elongate body using the securing mechanism proximate the surface of the organ for maintaining the tensioning member in a tightened state, including after the tightening mechanism has been disengaged from the tensioning member.

In some embodiments, the method further comprises: when the tension member is tightened by the tightening mechanism, a magnitude related to the tension force, a compression change of the volume portion, and/or a pressure change within the tumor is measured.

In some embodiments, securing comprises: applying a fastener to secure the first portion of the tension member to the second portion for an extended period of time sufficient to cause ischemia and/or necrosis in most or all tissue of the tumor when the volume portion is continuously compressed by the tension member and/or the tumor is forced to increase pressure therein during the period of time.

Unless otherwise explicitly defined or stated herein, all technical and/or scientific words, terms, or/and phrases used herein have the same or similar meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The illustrative embodiments of the methods (steps, procedures), devices (apparatus, systems, components thereof), equipment and materials illustratively described herein are exemplary and illustrative only and are not intended to be limiting. Although methods, devices, equipment, and materials equivalent or similar to those described herein can be used in the practice or/and testing of embodiments of the invention, the following illustrative methods, devices, equipment, and materials are described. In case of conflict, the patent specification, including definitions, will control.

Drawings

Some embodiments are described herein, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative description of some embodiments. In this regard, it will be apparent to those skilled in the art from this description, taken in conjunction with the accompanying drawings, how some embodiments may be practiced.

In the drawings:

FIG. 1 schematically illustrates a front cross-sectional view of an illustrative female uterus having different types of fibroids grown therein;

2A-2B schematically illustrate cross-sectional views of an illustrative tumor that is compressed, in particular radially, around the entire volume of the tumor (FIG. 2A) or around several volumetric portions of the tumor (FIG. 2B) using one or more tension members, according to some embodiments;

3A-3K schematically illustrate views of different exemplary fibroids treated with one or more tension members, according to some embodiments;

fig. 4 shows a block diagram of an exemplary method for treating a tumor within a body of a subject, according to some embodiments;

fig. 5A-5F schematically illustrate an exemplary scenario representing steps in an exemplary procedure for accessing uterine fibroids, in accordance with some embodiments;

fig. 6A-6J schematically illustrate exemplary scenarios representing steps in a method for treating a tumor within a body of a subject, according to some embodiments;

figures 7A-7F schematically illustrate exemplary scenarios representing steps in a method for treating a tumor within a body of a subject, according to some embodiments;

8A-8B schematically illustrate an exemplary scenario representing an alternative step to that shown in FIGS. 7A-7B, in accordance with some embodiments;

fig. 9A to 9I schematically illustrate exemplary scenarios representing steps in a method for treating a tumor within a body of a subject, according to some embodiments;

10A-10C schematically illustrate cross-sectional views of components of an example apparatus for passing a tension member around a tissue mass, according to some embodiments;

11A-11D schematically illustrate scenarios representing optional steps in an exemplary method for using the exemplary apparatus referred to in FIGS. 10A-10C, in accordance with some embodiments;

12A-12J schematically illustrate scenarios representing optional steps in an exemplary method for causing ischemia in a tumor, in accordance with some embodiments;

13A-13D illustrate views of an exemplary device for compressing a tumor according to some embodiments;

FIG. 13E illustrates a block diagram representing an exemplary design implementation of the device shown in FIG. 13A, in accordance with some embodiments;

13F-13I illustrate views of the device shown in FIG. 13A demonstrating changes in the range of motion of the trigger, in accordance with some embodiments;

14A-14C illustrate views of the proximal portion of the device shown in FIG. 13A that represent several scenarios of operating an exemplary tensioning mechanism, according to some embodiments;

15A-15C illustrate alternative deployment views of tension members in the apparatus shown in FIG. 13A, according to some embodiments;

16A-16C illustrate block diagrams and illustrations of exemplary design implementations of a tightening mechanism, according to some embodiments;

17A-17B illustrate views of the proximal portion of the device shown in FIG. 13A that represent several scenarios of operating an exemplary fixation mechanism, in accordance with some embodiments;

fig. 17C is a cross-sectional view of an exemplary fastener crimped around a portion of a tension member according to some embodiments;

18A-18D illustrate cross-sectional views of the distal portion of the apparatus shown in FIG. 13A, showing several scenarios of crimping fasteners, according to some embodiments;

19A-19B illustrate isometric views of the front (distal) portion of the device shown in FIG. 13A, according to some embodiments;

fig. 20 schematically illustrates an example apparatus including a tightening mechanism, a securing mechanism, and a tension member passing mechanism, according to some embodiments;

fig. 21 schematically illustrates an example kit including a first apparatus including a tightening mechanism and a securing mechanism and a second apparatus including a tension member passing mechanism, according to some embodiments; and

fig. 22 schematically illustrates an example robotic system including a tightening mechanism, a securing mechanism, and a tension member passing mechanism, according to some embodiments.

Detailed Description

Certain embodiments relate to devices and methods for affecting blood supply to a target tissue within a subject's body, and more particularly, but not exclusively, to devices and methods (e.g., minimally invasive devices and methods) for inhibiting a tumor, such as a uterine fibroid, by causing ischemia and/or necrosis. According to certain illustrative methods described herein, one or more tensile members are applied around or through a target tumor and placed under tension in a manner that triggers, supports, and/or induces tumor suppression.

In some embodiments, the tensioning member is deployed and directly affects (causes) a continuous pressure within the tumor, including but not limited to a pressure obtained from the accumulated compression force causing radial and/or volumetric tissue compression against the tumor, interstitial pressure within the tumor and surrounding host tissue, and capillary blood pressure of the tumor and proximate thereto, or any combination thereof, thus inhibiting blood flow into the tumor. Alternatively, additionally, or alternatively, the tension member is deployed across a blood vessel that nourishes the tumor, and is configured and sufficiently taut to impinge on the blood vessel and prevent blood flow therethrough. The prevention of blood supply to the tumor for several hours leads to fibroid ischemia and ultimately to necrosis of the tumor cells.

In some embodiments, one or more of the following (in any combination) may be included in the methods for triggering, supporting, and/or inducing tumor suppression:

a) a biocompatible material, optionally having a density greater than the original tumor density, such as hyaluronic acid, hydrogel, alginate, gelatin, BioGlue surgical adhesive (available from CryoLife of kenney, georgia), castor oil, Polyoxyethylene (POE), Pluronic F127 hydrogel, collagen cells (xenograph), or any other suitable material or combination of materials, is injected into the tumor. To improve material absorption and better insertion into the fibroid tissue, cuts/notches may be made in the fibroid and material may be inserted directly into the notches;

b) energy is directed to the tumor and/or surrounding tissue for raising the pressure in the tumor sufficiently to prevent blood supply to the tumor and cause ischemia in the tumor tissue. Energy may be delivered or maintained for an extended period of time sufficient to cause necrosis in all or most of the tumor tissue. The energy may include high intensity focused ultrasound, laser projection, direct or indirect hyperthermia or cryotherapy, or others.

c) A mechanical force is applied to the fibroid using a tensioning member, for example by tightening one or more sutures around and/or through the tumor. The suture may be an absorbable or permanent suture. Additionally or alternatively, a spring, rod, strap, clip, clamp, or any other force applying element may be used to increase the intrafibroid pressure; or

d) Pressure is applied directly on the blood vessels present on the surface of the tumor, such as by surrounding the blood vessels with the taught tension members (such as described above), thereby preventing blood flow therein and thus contributing to fibroid ischemia.

The foregoing methods may be performed in any of open surgery, laparoscopic surgery, or vaginal access surgery, including material injection and mechanical pressure application.

In some embodiments, in addition to causing an increase in pressure within the tumor by tightening the one or more tensioning members circumscribing the tumor, at least one tensioning member and/or at least one other device implanted around, adjacent to, or with the one or more tensioning members may be applied to directly affect or facilitate treatment directly from a remote location in the tumor and/or surrounding host tissue. The at least one tensioning member and/or other means may be applied to mark certain points, lines or portions around the tumor for directing focused energy thereto. Alternatively or additionally, the at least one tensioning member and/or other device may be applied to deliver energy (for hyperthermia or cryotherapy) and/or a substance to the tumor and/or its surrounding host tissue.

In some embodiments, as part of a method for compressing a fibroid using a taut tension member (e.g., suture), at least some of the following steps are performed (not necessarily in the order listed):

(a) inserting a distal end of a suture delivery device into an abdominal cavity;

(b) inserting a first needle (overtube) through the fibroid perimeter;

(c) pushing a second (inner) needle through the first needle and around the fibroid;

(d) transferring the suture through the second needle;

(e) the ends of the suture are provided in the abdominal cavity,

(f) optionally, repeating steps "b" through "e" at different angles (e.g., an angular shift of approximately 30, 45, 60, or 90 degrees of offset between sutures) on the fibroid; and

(g) the suture ends are pulled out of the body and an extracorporeal ligature is performed for each suture and the sutures are tightened on the external surface of the uterus, optionally using a knotter (knotter).

In some embodiments, as part of a method for compressing a fibroid using a taut tension member (e.g., suture), at least some of the following steps are performed (not necessarily in the order listed):

(a) inserting a distal end of a suture delivery device into an abdominal cavity;

(b) inserting a first needle through a uterine wall into a center of a fibroid;

(c) inserting a second needle through or around the fibroid perimeter;

(d) transferring the suture along a path from the first needle to the second needle (or vice versa);

(e) providing a suture end in the abdominal cavity;

(f) optionally, repeating steps "c" through "e" (e.g., 60 degree displacement between sutures) at different angles on the fibroid; and

(g) pulling the suture ends out of the body and performing an extracorporeal ligature for each suture and tightening the suture on the external surface of the uterus, optionally using a knot pusher.

As described further below, the tensioning member (e.g., suture) can be placed around the entire volume of the tumor (e.g., fibroid) (optionally including portions of other tissue surrounding the tumor (e.g., uterine tissue)) or around one or more smaller volume portions of the tumor. In some cases, it may be advantageous to surround the entire tumor (fibroid) and/or avoid passing the tension member through the tumor volume, as the density may increase dramatically when entering the fibroid and/or there may be the following risks: the tumor is cancerous such that puncturing therethrough increases the risk of cancer spreading to surrounding tissues and blood systems. Nonetheless, in some procedures, it may be advantageous to pass the tension member through the tumor, such as, for example, in an anatomy that imposes difficulties completely surrounding the tumor.

Fig. 2A-2B schematically illustrate cross-sectional views of an exemplary tumor being compressed using one or more tension members 10 extending around the entire volume V (fig. 2A) of the tumor or around several volumetric portions V1 and V2 (fig. 2B) of the tumor. In the illustrated figure, each tension member 10 extends around the entire perimeter of the volume V (fig. 2A) or the entire perimeter of the volume portions V1, V2 (fig. 2B). Furthermore, in the illustrated figures, each tension member 10 substantially surrounds a volume V or volume portion V1, V2, respectively, along a single plane (in particular, in fig. 2A and 2B, the plane corresponds to the plane of the drawing sheet).

Referring to fig. 2A, in some embodiments, a plurality of tension members 10 may be employed, and each tension member 10 may extend around at least a portion of the volume V. As discussed more fully below, in some cases, additional tension members 10 may extend along different planes that are angularly offset from one or more other tension members 10. For example, the additional tension member 10 may extend around the volume V along a plane that is at an angle to the plane of the drawing of fig. 2A. In various embodiments, when multiple tension members 10 are deployed, each tension member may wrap around more than half of the circumference (e.g., circumferential portion), more than two-thirds of the circumference (e.g., circumferential portion), or substantially all or all of the circumference (e.g., circumferential portion) of the tumor or volume V. Similarly, referring to fig. 2B, a plurality of tension members 10 may be employed about each of the volume portions V1, V2, and at least some of the additional tension members 10 may extend along or define a plane angularly offset from the illustrated tension members 10.

When under tension (such as may be caused by, for example, tightening, tying, stretching, or otherwise tensioning the tension members 10), each tension member 10 causes compression (e.g., radial compression) of the enclosed volume V or volume portions V1, V2. The tension force may be selected as discussed further below. For example, the tension may be selected, such as by selection, pre-selection, reservation, ordering (e.g., via instructions for using the tensioner), measurement, and/or calculation.

The plurality of tension members may be arranged around a volume or a volume portion of the tumor such that the combined effect of all of the tension members thereon is a compression toward the interior of the volume or tumor (e.g., toward the center) or toward the interior of the volume portion (e.g., toward the center). In some embodiments, each tension member 10 passes along a separate plane that traverses or crosses the tumor. In some embodiments, the tension members 10 pass through spaced apart, optionally evenly spaced apart, from each other relative to the center of the tumor or volume portion; in other words, the tension members 10 may be angularly offset from each other, and in some embodiments, the angular offset is regular and/or of equal magnitude relative to each pair of adjacent tension members 10.

Fig. 3A-3K schematically illustrate various views of different exemplary configurations of tumors (e.g., fibroids) formed within an organ (e.g., uterus) of a subject's body during or after treatment, according to some embodiments. In some embodiments, as shown in fig. 3A, one or more tensioning members 10 may be provided (e.g., implanted) around a fibroid when partially or completely traversing uterine tissue (e.g., healthy uterine tissue) surrounding the fibroid, particularly in the case of an interwall fibroid. In particular, fig. 3A depicts three separate tensioning members 10, each of which extends around the entire perimeter of the tumor and also encircles a portion of healthy uterine tissue. Each of the three tension members 10 substantially defines a circular profile that is limited to a single plane through the tumor. The planes intersect at a line passing through the center of the tumor. In the illustrated embodiment, each plane is angularly offset 60 degrees from each plane defined by the remaining two tension members.

Referring to fig. 3B-3D, additionally or alternatively, one or more tension members 10 may be provided through the fibroid tissue (such as through its center or near it). The number of tension members used can be determined as desired or as to the size or type of tumor, for example two, three, four or five tension members, or six tension members (fig. 3C), or eight tension members (fig. 3D), or more tension members are contemplated.

In some embodiments, one or more tension members 10 may be secured to the tumor and/or surrounding tissue by suturing or ligating around the tumor or volumetric region (e.g., as shown in fig. 2A and 3A) or volumetric portion (e.g., as shown in fig. 2B), or alternatively, the one or more tension members 10 may be secured using an anchor, such as anchor 11, for example, as illustrated in fig. 3E (showing the use of a separate anchor 11 for each of the six tension members 10) and 3F (showing a single tension member 10 extending tautly between two anchors 11 located at opposite sides of the tumor).

In various embodiments, the tension member 10 secured via anchors 11 (such as depicted in fig. 3E or 3F) may extend around the outer perimeter of the tumor. In other or additional instances, at least a portion of the tension member 10 can extend through an interior portion of the tumor. The anchors 11 may be used as an alternative system for securing the tension member(s) 10 to the tumor and maintaining tension in the tension members 10.

The tension member 10 may be configured in different forms and/or made of different materials. For example, in various embodiments, the tension member 10 may comprise a wire or suture (e.g., bioabsorbable or bioresorbable), a strap, an elongate fastener (e.g., a ratchet-type fastener such as a cable tie), or others.

Fig. 3G illustrates another embodiment of the tension member 10 configured as a coiled implant 15. The implant 15 is formed as an elastically extendable or compressible helical band configured to axially press (e.g., outward or inward) the boundaries of the tumor in opposite directions. For example, in the illustrated embodiment, the implant 15 includes a helical band (e.g., a compression spring) that has expanded outward relative to a natural or resting orientation. This expansion creates an inwardly directed bias. The implant 15 has passed through the centre of the tumour and its ends have been affixed to the outer limbs of the tumour. Thus, the inwardly directed bias of the implant 15 tends to axially compress the tumor in a longitudinal or axial direction defined by the implant 15. Each end of the implant 15 is biased in opposite directions-in this case, each end is biased inwardly in opposite directions toward the center of the tumor. In other embodiments, the implant may be secured to the tumor while in compression such that the implant 15 provides an outwardly directed bias in the longitudinal or axial direction and in the opposite direction. In some embodiments, one or more anchors 11 (such as depicted in fig. 3E, 3F) may be used to secure the ends of the implant 15 to the volumetric region and/or tumor to which the implant 15 is applied.

Fig. 3H depicts an arrangement similar to that of fig. 3A but having four tension members 10 instead of three, and depicts a top plan view rather than a perspective view. In particular, fig. 3H shows a tension member arrangement that provides a three-dimensional shape or compressive pattern that surrounds the tumor TM. In particular, a plurality of tension members 10 are placed around a volumetric region VR of an organ ORG including a tumor TM to define a three-dimensional shape. In the illustrated embodiment, the three-dimensional shape surrounds a portion of healthy tissue of the tumor TM and the organ ORG. In the illustrated embodiment, the shape is substantially spherical. The tension member 10 is tightened to reduce the size of the three-dimensional shape and thereby compress the volumetric region VR and the tumor TM.

In some embodiments, each tension member 10 is placed individually and sequentially around the tumor TM and tightened. That is, each tension member 10 is placed around the tumor TM and tightened, followed by the placement and tightening of each remaining tension member 10. Thus, in some cases, the first applied tension member 10 may define a substantially two-dimensional or planar shape, such as a circle or oval, and the size of the shape may be reduced due to the tightening of the tension member 10. Thereafter, additional tension members 10 may be placed around the tumor TM and tightened. When first placed around a tumor, the additional tensile member 10 may cooperate with the first placed tensile member 10 to define a three-dimensional shape that surrounds the tumor TM. The shape may be substantially oblong, with a first placed tension member 10 defining a smaller diameter and a second placed tension member 10 defining a larger diameter. As the second placed tension member 10 is tightened, the three-dimensional shape may decrease in size. In particular, the size of the two-dimensional shape defined by the first placed tension member 10 may remain substantially unchanged in its stressed state, while the size of the two-dimensional shape defined by the second placed tension member 10 may be reduced. The three-dimensional shape collectively defined by the first placed tension member 10 and the second placed tension member 10 may likewise be reduced and may become less obround or more equally proportional. For example, the three-dimensional shape collectively defined by the first placed tension member 10 and the second placed tension member 10 may transition from a shape that is substantially oval or substantially prolate spheroid to a shape that is substantially spherical. As more tension members 10 are placed and tightened, the compressive three-dimensional shape surrounding the tumor TM may increasingly resemble a sphere, or in other cases may resemble some other three-dimensional shape, such as a reduced diameter variation that may correspond to the irregular three-dimensional shape originally defined by the tumor TM, for example.

The tension members 10 may be referred to individually and/or collectively as a medical device, or an exogenous device with respect to the patient. The term "patient" is used broadly herein to refer to any suitable animal subject. The patient may be, for example, a human or any other mammal.

In other embodiments, the tension members 10 may be placed in sequence and tightened simultaneously. For example, in some embodiments, the tension member 10 may be positioned around the volumetric region VR to substantially define a spherical three-dimensional shape. Then, the tension members 10 may be tightened simultaneously such that the size of the spherical shape is reduced, for example such that the radius of the sphere is reduced.

In still other embodiments, multiple tension members 10 may be placed simultaneously, and in still other embodiments, they may be tightened sequentially or simultaneously. For example, in some embodiments, a mesh, net, or array comprising a plurality of tension members may be placed around a tumor (e.g., a fibroid). In some cases, a mesh, net, or array may be applied at the exterior of an organ (e.g., the uterus) in which the fibroid is embedded, and thus may also surround a portion of the organ tissue. Once in place around the tumor and defining the three-dimensional shape of the first size, the constituent tensioning members can be tightened either sequentially or simultaneously, thereby contracting, tensioning, compressing, reducing the profile of, or otherwise transitioning the three-dimensional shape to a second size that is smaller than the first size and compresses the tumor. In some embodiments, the array may be similar to the tension member pattern depicted, for example, in fig. 3I or 3J, but may be accomplished without inserting any tension members through the organ (e.g., uterus) tissue. Instead, the tumor (e.g., fibroid tumor) may be circumscribed by a tension member/tension member array that is completely external relative to the outer surface of the organ (e.g., uterus).

With further reference to fig. 3H, in the illustrated embodiment, four discrete tension members 10 are disposed at approximately 45 degree angular offsets around a volumetric region VR of an organ ORG in the subject's body, the organ ORG including the tumor TM. Each tensioned member 10 is circular in form and defines a discrete plane. In the illustrated embodiment, the planes intersect at a single line passing through the center of the volumetric region VR and/or the tumor TM. In various embodiments, the minimum angular offset between adjacent tension members 10 may be no less than 10, 15, 20, 25, 30, 45, or 60 degrees.

When tightened, each of the tension members 10 may apply an inwardly directed pressure along a separate compression line to tissue within the volumetric region VR — i.e., in the illustrated embodiment, to circumscribed portions of tissue of the tumor and organ ORG. In the illustrated embodiment, the compression force along each compression line is directed inwardly or toward the interior of the tumor. Furthermore, in the illustrated embodiment, the compression force is radially compressive and directed toward the center of the tumor TM. In some embodiments, at least one of the tension members 10 passes over and compresses a blood vessel 17 (e.g., a capillary vessel) feeding the tumor, thereby partially or completely occluding the blood vessel 17 for reducing or preventing, respectively, oxygenated blood from reaching the tumor tissue. In some embodiments, at least one of the tension members 10 is deployed over a predefined channel that traverses one or more blood vessels.

Fig. 3I illustrates another example of a tension member arrangement in which different three-dimensional compression patterns are formed. In this example, five discrete tension members 10 are arranged in a substantially parallel manner around a volumetric region VR of an organ ORG in the body of the subject, the organ ORG including a tumor TM. Each tension member 10 defines a substantially circular two-dimensional form and defines discrete planes. In the illustrated embodiment, the planes are parallel to each other. The four tension members 10 on the left may each direct a compression force towards the interior of the tumour. However, in some cases, some or all of the tension members 10 may not direct the compression force to the center point of the tumor TM, but may direct the compression force to a centerline through the tumor TM. Furthermore, the compression force of the rightmost tension member 10 may not be directed exclusively toward the interior of the tumor, but may provide an inwardly directed compression force to the circumscribed portion of the organ tissue adjacent the tumor TM. Nonetheless, all of the tension members 10 and the volumetric or three-dimensional compression they provide to the volumetric region VR may generate increased pressure within the tumor TM.

In the illustrated embodiment, each of the five tension members 10 may define a substantially two-dimensional compressive shape (e.g., a circle) that directs force inwardly relative to the volumetric region VR, and the tension members 10 may collectively define a three-dimensional compressive shape that volumetrically compresses the volumetric region VR. In particular, in the illustrated embodiment, the three-dimensional compressive shape is substantially spherical.

Fig. 3J shows seven discrete tension members 10, each of which circumscribes a volumetric region VR of an organ ORG in the body of the subject, the organ ORG including a tumor TM. Each tension member 10 is circular in shape and defines a discrete plane; the planes are angularly offset from each other by an acute angle. In the illustrated embodiment, these planes all intersect at a line outside the volumetric region VR and/or outside the tumor TM. The three-dimensional compressive shape collectively defined by the tension members 10 is substantially spherical, or substantially spherical with angularly truncated ends.

Fig. 3K shows a single tension member 10 circumscribing a volumetric region VR of an organ ORG in the subject's body, the organ comprising a tumor TM. The tension member 10 defines a helical shape that extends along the length of the volumetric region and, for example, extends through approximately 5 full turns or 1800 degrees of angular rotation in the illustrated embodiment. In other embodiments, a different number of turns is contemplated. For example, in various embodiments, the tension member 10 may extend around the tumor TM through an angular rotation of no less than about 360, 540, 720, 900, 1080, or 1260 degrees.

In some embodiments, the tension member 10 is placed around the volumetric region VR to define a three-dimensional shape, such as a sphere. The tension member 10 may be tightened to reduce the size of the three-dimensional shape. For example, the tension member 10 may be a suture thread that is wrapped multiple times around the volumetric region VR to substantially define a sphere, oblate spheroid, prolate spheroid, or other three-dimensional shape. The taut suture can then be pulled to reduce the size (e.g., volume) of the three-dimensional shape and compress the tumor TM. The suture may be tied or otherwise secured in a tightened state, such as in the manner discussed below.

Note that fig. 3A to 3K are schematic and do not necessarily demonstrate all the details of the compressed arrangement. For example, in some cases, the amount of organ (e.g., uterine) tissue present in the volumetric region VR may be relatively less than the amount shown. Furthermore, in some embodiments, the tension provided by the tension member 10 may be very large, such that the shape of the tumor TM may be altered due to the presence of the tension member 10. In many cases, more generally, the tumor TM and/or volumetric region VR may bulge outward between adjacent tension members 10. Thus, the neat spherical arrangement of tumor TM and volumetric region VR, such as shown in each of fig. 3H-3K, may instead be less regular and include an outward bulge between each set of adjacent tensile members 10 (fig. 3H-3J) or between adjacent turns of tensile members 10 (fig. 3K).

Fig. 4 shows a block diagram of an illustrative method 50 for treating a tumor (optionally a uterine fibroid) within a subject's body, optionally resulting in the placement of a taut tension member provided around and/or through the tumor, as shown, for example, in fig. 2A, 2B, 3A-3F, and 3H-3K, or any combination thereof. The tumor may be transmural, serosal, or submucosal (as shown in fig. 1), and the method 50 may involve treating multiple tumors or clusters of tumors, which may be of various forms, sizes, shapes, and/or types, simultaneously, sequentially, concurrently, or in any combination.

For example, with respect to simultaneous treatment of tumor clusters, it should be noted that while the previous examples depict a single tumor or a portion of a single tumor TM within volume V (fig. 2A), volume region VR (fig. 3H-3K), or volume portions V1, V2 (fig. 2B), in other cases multiple tumors (e.g., tumor clusters) may exist within volume V, volume region VR, or volume portions V1, V2. Thus, in some cases, a medical device (such as a plurality of tension members 10) may encapsulate, obscure, encircle, enclose, surround, or otherwise extend around the plurality of tumors, such as in the illustrative three-dimensional pattern previously discussed. The tension member 10 may be tightened or otherwise generate a compression force that compresses the plurality of tumors, thus treating all tumors surrounded by the tension member 10 simultaneously.

In other or additional instances, multiple tumors may be treated by individually wrapping each tumor with one or more tensioning members and tightening the one or more tensioning members (in a manner such as described previously and below). For example, a method may include performing method 50 one or more times with respect to a first tumor, and independently repeating method 50 one or more times with respect to a second tumor; repeating method 50 independently one or more times for each of the second tumor and the third tumor; repeating method 50 one or more times for each of the second tumor, the third tumor, and the fourth tumor; and the like.

With continued reference to fig. 4, the illustrated method 50 includes steps or stages that are performed in sequence in the illustrated embodiment, as indicated by the arrows in fig. 4. In other cases, one or more of these stages may be performed simultaneously or in a different order. At stage 51, a volumetric region of the tumor is defined, such as, for example, volume V of fig. 2A, volumetric portion V1 or V2 of fig. 2B, or volumetric region VR of fig. 3H-3K. The volumetric region may be defined in any suitable manner. For example, a practitioner may define a volumetric region by visually inspecting a tumor (such as a uterine fibroid) that may be covered by organ tissue (e.g., a uterine wall) via any suitable imaging system. In some cases, the laparoscope may include an imaging system. Thus, defining a volumetric region may require identifying the region around which the practitioner intends to pass one or more tension members. In other or additional instances, defining the volumetric region may include actually placing the one or more tension members around the volumetric region, such as described with respect to stage 52.

At stage 52, a tension member (e.g., tension member 10) is passed around the volumetric region, optionally in a close fit or on or along the perimeter of the volumetric region. Any suitable method of passing the tension member around the volumetric region is contemplated. For example, several illustrated methods for such placement are discussed below with respect to fig. 5A-12J. The term "close fit" is used herein to indicate that the tension member is near or in close proximity to the volumetric region. For example, in various embodiments, a close fit may represent a distance having a value no greater than 30%, 25%, 20%, 15%, 10%, or 5% of the maximum diameter of the tumor.

At stage 53, the tension member is tightened (such as at a selected tension) so as to affect compression (e.g., radial compression) on the volumetric region for increasing pressure within the tumor. The increased pressure may be of one or more kinds.

For example, increased pressure within a tumor may be associated with: (1) a total compression force applied to the tension member, or alternatively to several tension members, and (2) a total surface area of the tumor or a volumetric area of an organ encapsulating the tumor or portion thereof. For example, the pressure may be calculated as the total pressure exerted by the tension member divided by the surface area of the volumetric region physically contacted by the tension member. In other or additional cases, the pressure may be calculated as the total pressure divided by the total surface area of the volumetric region. The pressure may be ambient or absolute. The pressure may be the average pressure over the entire tumor volume, or the pressure measured adjacent to the compression line or surface caused by the tightened tension member(s). In some embodiments, the increased pressure within the volumetric region and/or within the tumor is greater than about 20 mmHg, optionally greater than about 50 mmHg, optionally greater than about 100 mmHg, optionally greater than about 200 mmHg, optionally between 30 mmHg and 200 mmHg.

Additionally or alternatively, the increased pressure within the tumor may be related to capillary blood pressure. For example, capillary pressure may be increased within a volumetric region or as measured at a downstream location relative to the vessels (capillaries or arteries) directly feeding the tumor. As a result, the elevated capillary pressure may inhibit or prevent oxygenated blood from the blood vessels (capillaries or arteries) directly feeding the tumor from feeding oxygenated blood into the volumetric region. In some embodiments, the increased pressure within the volumetric region and/or within the tumor causes a local capillary pressure of greater than about 5 mmHg, optionally greater than about 10 mmHg, optionally greater than about 20 mmHg, optionally greater than about 25 mmHg, optionally greater than about 50 mmHg, optionally between 10 mmHg and 22.5 mmHg.

Additionally or alternatively, the increased pressure within the tumor may be related to the interstitial fluid pressure measured in the tumor and/or in the surrounding host tissue, which is known to cause a physical barrier for the delivery of cell nutrients and small molecules into the tumor. In some embodiments, the increased pressure within the volumetric region and/or within the tumor causes a local interstitial pressure greater than about 0.1 mmHg, optionally greater than about 0.5 mmHg, optionally greater than about 1 mmHg, optionally greater than about 4 mmHg, optionally greater than about 10 mmHg, optionally between 0.1 mmHg and 5 mmHg.

Thus, in various embodiments, the increased pressure in the volumetric region may be one or more of: such as increased tension applied across the surface area (e.g., contact area or total surface area) of the volumetric region, increased capillary pressure within the volumetric region, and/or increased interstitial fluid pressure within the volumetric region. For each applicable kind of pressure sufficient to cause ischemia within the volumetric region and/or within the tumor, the increased pressure of the one or more kinds may be above a suitable pressure threshold. When the specified pressure is maintained above the ischemic threshold for a sufficient period of time, necrosis of the affected tumor tissue results. As discussed elsewhere herein, the elevated pressure (e.g., above the ischemic pressure threshold) can be maintained for a period of time sufficient to achieve necrosis of the tumor tissue (e.g., at least a majority of the tumor tissue, substantially all of the tumor tissue, etc.). In each case, the period is at least 1 hour and/or not less than 4, 5, 6, 7, or 8 hours. In each case, maintaining elevated pressure for no less than 1, 2, 3, 4, 5, 6, or 7 days; not less than 1, 2, 3 or 4 weeks, or not less than 1 or 2 months.

The traversing at stage 52 may involve a plurality of tension members, optionally along separate paths around and/or through the defined volume portion. If the definition at stage 51 is for multiple volume portions, the passing at stage 52 may involve one or more of the tension members surrounding and/or passing through one of the volume portions and the other of the tension members surrounding and/or passing through another of the volume portions.

Tightening at stage 53 may involve increasing the pressure inside the tumor above capillary blood pressure by inward or radial compression, and the increased pressure may be continuously maintained to cause ischemia in most of all tissues of the tumor. Once the pressure within the volumetric region (e.g., capillary blood pressure) has risen to a sufficient level, the flow of blood into the volumetric region will be reduced or stopped. Thus, ischemia in most or all tissues of a tumor can be substantially transient when a threshold pressure is achieved that exceeds, for example, the capillary systolic pressure. This ischemic state may be maintained until tissue necrosis is fully or partially achieved. If the defined volume portion is for most or all of the volume of the tumor (e.g., volume V of fig. 2A), the tightening at stage 53 may be configured to affect spherical radial compression of the tumor by one or more of the tension members 10.

The tension members (optionally the tension members 10) that may be suitable for use with the method 50 may be configured as elongate filaments, cables, wires, ribbons, and the like. For example, in various embodiments, the tension member 10 may comprise a suture cable or a suture wire. The tension member in use may comprise a material comprising at least one of: implant-grade metal alloys, implant-grade polymers, implant-grade textiles, and biodegradable materials. In various embodiments, the tension member may be configured with a yield strength or maximum tension of at least 25 newtons (about 2.55 kg), at least 40 newtons (about 4 kg), at least 50 newtons (about 5.1 kg), at least 80 newtons (about 8.16 kg), or at least 120 newtons (about 12.24 kg). In various embodiments, the tension member 10, or each tension member 10 if multiple tension members are used, may be tightened or otherwise tensioned to a tension of no less than 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 110, or 120 newtons.

The stage 51 of defining the volume portion may comprise selecting an entrance opening and an exit opening at the organ surface surrounding and/or passing through the tumour for passing the tension member between and through the entrance opening and the exit opening; it may further comprise defining a plane across the volume portion and/or the tumour between the entry point and the exit point; and it may also include defining a volume portion as a whole. Alternatively and alternatively, the defined stage 51 may be considered an optional step that the user (surgeon) may choose to ignore without compromising the integrity of the method 50. The stage 51 of defining one or more volume portions may include, may follow or may be followed by, or may be replaced by: one or more channel lines (e.g., channel lines 204 shown in fig. 7A, for example) are defined between the inlet and outlet openings formed on the tumor and/or on tissue surrounding the tumor for passage of the tensioning member therealong. When describing the passage of a tension member between an inlet opening and an outlet opening, an exemplary procedure may include first advancing the tension member through the outlet opening, through the intermural region of the uterus, and then through the inlet opening (this is a retrograde direction relative to an elongate member (such as a stylet or needle) applied for creating a surgical channel between these points to draw the tension member therethrough). Nonetheless, the tension member extends between the inlet opening and the outlet opening, and thus may be characterized as passing between the inlet opening and the outlet opening. In other embodiments, it is contemplated that the tension member may pass in the opposite direction, i.e., enter through the inlet opening and exit through the outlet opening.

The at least one defined access line optionally protrudes across the blood vessel 17 feeding the tumor such that tightening of the tension member passing along the access line directly affects occlusion of the blood vessel (e.g., as shown in fig. 3H). Defining 51 may include calculating, constructing, and/or optimizing a spatial arrangement of the plurality of tension members to affect occlusion to prevent the estimated maximum volume of blood from feeding the tumor when tightened and/or to affect the estimated maximum radial compression on the volume portion.

Fig. 5A-5F schematically illustrate an exemplary scenario representing steps in an exemplary procedure for accessing a uterine fibroid (shown in fig. 5A) in a subject's body for applying a tension member to the uterine fibroid, such as by performing one or more variations of method 50 or similar methods. A uterine manipulator 20 (with or without an expandable (e.g., inflatable) member 21 at its distal end) is deployed in the uterus via the vagina (fig. 5B), engaging the uterine wall, (and the expandable member 21 optionally partially conforms to the shape imposed by and/or expanded shape affecting the inner boundary of the uterine wall (fig. 5C)). Uterine manipulator 20 may then be applied to contour, displace and/or point the uterus or a portion thereof in different directions such that an operator may apply uterine manipulator 20 to displace and direct uterine fibroids closer to and/or toward the abdominal wall (as shown in fig. 5D), for example, if access to the fibroids is to be surgically performed to the abdominal cavity via the abdominal wall (optionally with CO for ease of operation, optionally)₂Inflated).

In other words, in certain methods, uterine manipulator 20 can be used to achieve a desired orientation of the fibroid. Manipulation of the fibroid via uterine manipulator 20 may direct the fibroid closer to the abdominal wall and/or more easily accessible via laparoscopic surgery, as shown in fig. 5D-5F. The use of any suitable uterine manipulator 20 is contemplated, including those known in the art and those yet to be devised. Any suitable procedure for providing surgical access to the uterus via the abdomen is also contemplated, including any suitable procedure for providing laparoscopic access.

Fig. 5E and 5F illustrate other steps that may be employed in some methods. In particular, in some cases, uterine manipulator 20 can be used in conjunction with minimally invasive surgery (such as laparoscopy). As shown in these figures, some methods may include: using laparoscopic port 22 and laparoscopic instrument 23, a surgical passageway is created laparoscopically into the abdomen of the patient and to the surface of the uterus disposed in the abdominal cavity. The laparoscopic device 23 may be configured for delivering and/or passing one or more tensioning members in the uterus around the fibroid. Illustrative embodiments of such laparoscopic devices are described below.

Fig. 6A to 6J schematically illustrate exemplary scenarios representing steps or stages in a method for treating a tumor in a subject's body. In some cases, these stages may be performed after a direct pathway is created (e.g., in a minimally invasive manner) from outside the body of the subject (patient) to the tumor (such as, for example, via a method as depicted in fig. 5A-5F). Minimally invasive access to the tumor can be created by transvaginal surgery, endoscopy, laparotomy, or laparoscopy.

Figure 6A illustrates the use of a laparoscope with minimally invasive access using the laparoscopic port 22. Via surgically created access to the uterus, the outer tube 100 is positioned at the entrance opening EO across the tissue wall (uterine tissue) surrounding the tumor (fibroid) such that the distal end 101 of the outer tube 100 is located adjacent to the transverse limb TE of the fibroid (fig. 6A). The curved needle 102 is then pushed through the lumen of the outer tube 100 until the distal portion 103 of the curved needle 102 protruding from the outer tube 100 regains the curved shape (fig. 6B).

The curved needle 102 forms a portion of the channel 104 around at least half of the perimeter of the fibroid. The stylet 105 is then pushed distally through the curved needle 102 via the inlet opening EO, passing through the curved distal portion 103 of the needle 102 and out of the uterine tissue at the outlet opening EX, thereby completing the formation of the passage 104 around the volume V. Fig. 6D schematically illustrates the same scenario as in fig. 6C, with a virtual representation of the channel 104 and the volume portion V, without showing the outer tube 100, the curved needle 102 and the stylet 105 present as shown in fig. 6C for ease of explanation only. The channel 104 fits tightly and encloses a volume portion V of the fibroid, which extends between the inlet opening EO and the outlet opening EX, surrounding the tumour and optionally some uterine tissue surrounding the tumour.

The stylet 105 includes a means, such as a loop 106, at its distal end configured to facilitate securement to a tension member, which may be in the form of a suture cable or suture wire 107. For example, as shown in fig. 6F, the proximal end 108 of the stylet 105 can include a loop 106 through which the tension member 107 has been passed prior to passing the stylet 105 through the curved needle 102. The loop 106 may, for example, retain a middle portion of the tension member 107 therein such that the tension member 107 is folded into two lengths and the opposite ends of the tension member at the ends of each length are left at the exterior of the patient during passage of the stylet 105 and the middle portion of the tension member 107 through the passage 104 around the fibroid.

Referring again to fig. 6E, the stylet 105 may be pushed through the outer needle 100 and the inner needle 102 along a curved path around the fibroid. The distal end of the stylet 105 can be sufficiently sharp to pierce the final portion of uterine tissue to complete formation of the channel 106 in some cases, as previously mentioned. As shown in FIG. 109, in some embodiments, the laparoscopic grasper 109 is inserted into the body (e.g., via the laparoscopic port 22) and manipulated to grasp the distal end of the stylet 105. The grasper 109 may be proximally withdrawn while holding the stylet 105 to drag the stylet 105 and the intermediate portion of the tension member 107 coupled thereto by the channel 104. Finally, after passing through the passage 104, the proximal end 108 of the stylet 105 is pulled from the exit opening EX (fig. 6E) until the middle portion of the stylet collar 106 and tension member 107 is clear of the uterine tissue (fig. 6F). Thus, the tension member 107 may extend around the volume V between and through the inlet opening EO and the outlet opening EX. The pulling of the stylet 105 can continue until a portion (i.e., a middle portion) of the tension member 107 is disposed outside of the subject's body (fig. 6G). The outer tube 100, curved needle 102, and stylet 105 may be removed, thereby holding only the tension member 107 in place along the channel 104 (fig. 6H). If the tension member 107 extends in one direction and back along the channel 104 (as shown in fig. 6H), it may then be adjusted in such a way that the tension member 107 will follow the channel 104 in only a single direction (as shown in fig. 6I), or in other words, so that only a single strand of the tension member 107 passes through the channel 104. For example, in some embodiments, as previously discussed, two lengths of the tension member 107 pass through the channel 104 in fig. 6H due to the folded-back arrangement of the tension member 107. One of these lengths may be pulled at the exterior of the patient such that the length passes through the channel 104 (e.g., in the direction of the inlet opening EO to the outlet opening EX) and is eventually pulled out of the patient through the laparoscopic port 22 to the arrangement depicted in fig. 6I.

Referring to fig. 6J, in certain embodiments, the tension member 107 is then tightened along its length, for example, with a selected tension, so as to affect compression (e.g., radial compression) of the volume portion to increase pressure within the tumor. A first portion 110 of the tension member 107 protruding from the inlet opening EO is secured to a second portion 111 of the tension member protruding from the outlet opening EX, such as via a suture knot and/or fastener (e.g., a crimped fastener, as discussed elsewhere herein). The tension members 107 may be sufficiently taut to raise the pressure within the volumetric region V and/or fibroid, alone or in combination with additional tension members 107 subsequently placed in a similar manner, by an amount sufficient to cause ischemia of the volumetric region V and/or fibroid, as previously discussed. Tightening may be maintained after the tension member 107 is secured, at least until most or all tissue of the tumor is necrotic, as previously described. The described fixation of the first and second portions of the tensioning member may be achieved outside the boundaries of a tumour (e.g. a fibroid tumour) and/or optionally outside the boundaries of an organ containing the tumour in the body (e.g. a uterus).

Fig. 6J is schematic and does not necessarily depict the amount of tension applied to the fibroid. In some cases, the amount of tension supplied by the tension member 107 is sufficient to dig into, embed, squeeze, deform, reshape, or otherwise alter the fibroid.

The illustrative method stages depicted in fig. 6A-6J will now be further described in additional or further terms. The illustrated method is performed via a system and/or apparatus that includes a first needle, an elongate member, an access tube (access tube), or a tubular member 100. The first needle 100 may include a sharpened (beveled, pointed, etc.) distal tip to facilitate entry into the uterus to a first depth. The first needle 100 may define an inner lumen. The first needle 100 may be formed of any suitable material, such as, for example, stainless steel. In some cases, the first needle 100 may be rigid so as to resist lateral deflection thereof during passage through the patient and/or organs thereof.

The system or device may further include a second needle, elongate member, access tube or tubular member 102 having an outer dimension (e.g., outer diameter) of a size sufficient to translate, slide, advance and retract or otherwise be movable within the lumen of the first needle 100. The second needle 102 may include a sharpened (beveled, pointed, etc.) distal tip to facilitate a second length of the channel 104 through the uterus and/or (in some cases) through the fibroid to surround a volumetric region of the tumor. In some embodiments, the second needle 102 includes a pre-curved distal end. In some embodiments, the distal end 103 of the second needle 102 may be resiliently flexible. In some embodiments, the stiffness of the first needle 100 is sufficient to maintain the first needle 100 in a substantially straight orientation while the pre-curved distal end or portion 103 of the second needle 102 is maintained within the lumen of the first needle 100. For example, in some embodiments, the pre-curved distal end 103 of the second needle 102 may be positioned within the first needle 100 in a straightened orientation. The first needle 100 may be sufficiently rigid to maintain the pre-curved distal end 103 of the second needle 102 in a straightened orientation as the second needle 102 is advanced through the lumen of the first needle 100. Further, during retraction of the second needle 102 into the first needle 100 after use of the second needle 102, the first needle 100 may be sufficiently rigid to assist the distal end 103 of the second needle 102 in transitioning from the natural pre-bent state back to the straightened state. The second needle 102 may be formed of any suitable material, such as, for example, stainless steel, nitinol, various plastics, and the like. In some embodiments, the second needle 102 may desirably be sufficiently rigid to easily pass through the uterus and/or fibroid tissue. The second needle 102 may be resiliently flexible so as to easily and naturally transition from a temporary or constrained straightened orientation to a pre-bent orientation when the second needle 102 is delivered through the distal end of the first needle 100. The second needle 102 may further define a lumen therethrough.

The system or device may further include an elongated member for coupling with the suture, which may be referred to as a suture passer or stylet 105. The stylet 105 may be appropriately sized to translate, slide, advance, and retract, or otherwise be movable within the lumen of the second needle 102. In the illustrated embodiment, the stylet 105 can be longitudinally rigid so as to be longitudinally advanceable through the first and second needles 100, 102. The stylet 105 can be further laterally bendable or deflectable so as to be readily passable through the bent distal region 103 of the needle 102. In the illustrated embodiment, the longitudinal stiffness of the stylet 105 is such that upon exiting the pre-curved portion 103 of the second needle 102, a distal portion of the stylet 105 forms a substantially straight path, while more of a proximal portion of the stylet 105 remaining within the curved portion 103 is curved to match the curved profile of the lumen of the second needle 102. In some embodiments, the distal tip of the stylet 105 can be sufficiently sharp or otherwise configured to pierce the uterus and/or (in some cases) the fibroid tissue.

The system may be used, for example, in minimally invasive laparoscopic surgery. For example, surgery (such as depicted in and described with respect to fig. 5E and 5F and/or additional fig. 5A-5D) may be performed to provide access to the uterus and fibroids. Via the laparoscopic port 22, a first needle 100 may be introduced to the patient and into the uterus, as depicted in fig. 6A. In particular, the sharpened distal tip of the first needle may form the inlet opening EO at the uterine surface. The distal tip of the first needle 100 may be further advanced through the uterus to a depth suitable for deploying the second needle 102 so that the second needle 102 may extend around the outer perimeter of the fibroid.

Referring to fig. 6B, the second needle 102 may be advanced through the lumen of the first needle 100 while its pre-curved distal end 103 is held (e.g., via the inner surface of the first needle 100 defining its lumen) in a straightened state. The second needle 102 may be advanced distally through the distal opening of the first needle 100. As the second needle 102 exits the first needle 100, the distal region 103 of the second needle 102 may naturally, automatically, and/or elastically return to its pre-formed curvature, and thus may form a curved path around the fibroid as the second needle 102 is further advanced distally through the distal opening of the first needle 100. The preformed curvature may extend around at least a portion of a perimeter of the fibroid. For example, in various embodiments, the pre-curved distal region 103 can form a curved path that curves through an angle of about no less than 30, 45, 60, 75, 90, 135, 180, or 270 degrees. In the illustrated embodiment, the angle is approximately 180 degrees. In various embodiments, the pre-curved distal region 103 can form a curved path that extends approximately no less than one-quarter, one-third, one-half, two-thirds, or three-quarters of the circumference (e.g., circumferential portion) of the fibroid.

In some embodiments, the pre-curved distal region 103 may be advanced until the distal end of the second needle 102 pierces the outer surface of the uterus. In the illustrated embodiment, the pre-curved distal region 103 instead extends only through the intermural uterine tissue and stops short of the upper surface, as shown in fig. 6B.

Referring to fig. 6C, in some embodiments, the stylet 105 can be advanced distally through the second needle 102. The distal end of the stylet 105 can pierce the uterine tissue to form an exit opening EX through the outer surface of the uterus. Referring to fig. 6D, each of the first needle 100, the second needle 102, and the stylet 105 may surround a separate leg of the volume V and the fibroid passage 104. In other words, the first needle 100, the second needle 102, and the stylet 105 may collectively form the channel 104 around the fibroid.

Referring to fig. 6E and 6F, as previously discussed, the proximal end 108 of the stylet 105 can be coupled with the tension member 107. Thus, the stylet 105 can be pulled, for example, via the grasper 109, which can pass or otherwise pass the tension member 107 along the path or channel 104. In the illustrated embodiment, two lengths of folded tension member 107 pass through inlet opening EO, around the fibroid (e.g., only through the intermural uterine tissue) and through outlet opening EX along passage 104. One of the lengths of the tension member 107 may continue to pass through the channel 104 in the same direction until only one length of the tension member 107 protrudes through the inlet opening EO and only the other length protrudes through the outlet opening EX, as shown in fig. 6I. The two lengths of tension member 107 may be fixed and tightened in a manner such as previously discussed and as schematically depicted in fig. 6J.

In some methods, one or more additional tension members 107 are provided around the fibroid by repeating the method. The additional tension members 107 may create a three-dimensional compressive arrangement, such as previously described, for example, with respect to fig. 3A, 3H-3K. Other devices, systems, and methods discussed below may also be used to place multiple tension members around a fibroid, such as by repeating the disclosed steps using additional tension members. The additional tension members may create a three-dimensional compressive arrangement such as previously described, for example, with respect to fig. 3A, 3H-3K.

Fig. 7A-7F schematically illustrate exemplary scenarios representing steps or stages in another illustrative method for treating a tumor. The depicted phase may be performed after a direct access is formed (e.g., in a minimally invasive manner) from outside the body of the subject (patient) to the organ surrounding the tumor (uterus), as shown, for example, in fig. 5A-5F. Minimally invasive access may be created by transvaginal surgery, endoscopy, laparotomy, or laparoscopy. An application apparatus 299 comprising an outer tube 200, a curved needle 202, a stylet 205, and optionally a crimping mechanism or device 209. In some cases, there is also a tension member 207 within the device 299.

As shown in fig. 7A, the outer tube 200 is advanced into the tissue wall TW of the uterine tissue surrounding the tumor (e.g., fibroid). In particular, the sharpened distal end of the outer tube 200 may form an inlet opening EO through the outer surface of the uterus. In the illustrated embodiment, the free end of the tension member 207 hangs out of the distal opening of the outer tube 200 and may be left at the exterior of the uterus (while still remaining at the interior of the patient) as the distal end of the outer tube 200 is advanced into the uterine tissue. Once the distal end of the outer tube 200 is in place, as shown in fig. 7A, the curved needle 202 is pushed through the lumen of the outer tube 200 until a distal portion 203 of the curved needle 202 protruding from the outer tube 200 resiliently regains the curved shape.

As it is advanced distally, the curved needle 202 forms a channel 204 around a volumetric region VR including the tumor (in this example, the entire tumor may be disposed in the volumetric region VR, although according to some embodiments, only a portion of the tumor may be surrounded by the channel 204, if desired). Stylet 205 is then pushed distally through curved needle 202 along channel 204 until exit opening EX is formed and protrudes therefrom outside of the uterine tissue (while still within the subject's body), and formation of channel 204 can thereby be completed (if it has not been previously fully formed by curved needle 202). Thus, channel 204 can be said to extend from inlet opening EO to outlet opening EX in another portion of the uterine tissue.

The stylet 205 includes a means, such as a loop 206, at its distal end configured to facilitate securement to a tension member 207, which in the illustrated embodiment is in the form of a suture-use wire. In some embodiments, the stylet 205, or at least the distal end thereof, may be formed of a resiliently flexible material. Thus, the loop 206 may remain in a low-profile orientation when positioned within the lumen of the curved needle 202, and may expand to the open profile of fig. 7A when advanced out of the distal end of the curved needle 202. The loop 206 may be forced back to a low profile configuration as it is drawn proximally back into the curved needle 202, which may enhance the grip of the loop 206 on the tension member 207.

As shown in fig. 7B, the end portion of the tension member 207 that is suspended or otherwise extends out of the outer tube 200 at an early stage of the procedure may be coupled to the loop 206. For example, an end portion of the tension member 207 may pass through the loop 206 by an amount sufficient to ensure that the tension member 207 is gripped by the loop 206. In some embodiments, a laparoscopic grasper or other suitable device may be used to manipulate the tension member 207 to pass it through the loop 206.

Then, after passing through the passage 204, the stylet 205 is pulled back (in a direction from the outlet opening EX towards the inlet opening EO) until the loop 206, as coupled with the end portion of the tension member 207, exits the uterine tissue via the inlet opening EO into the outer tube 200. This action may draw the tension member 207 distally through the outer tube 200, through the channel 204, and back into the outer tube 200 in the proximal direction, such that the tension member 207 extends around the volumetric region VR between and through the inlet opening EO and the outlet opening EX (as shown in fig. 7C).

The stylet 205 is pulled completely through the outer tube 200 (fig. 7D) until both the first portion 210 of the tension member 207 protruding from the inlet opening EO and the second portion 211 of the tension member 207 protruding from the outlet opening EX are positioned outside the subject's body. Then, in the illustrated embodiment, the crimping device 209 (which is configured as a tubular crimping element formed from a ductile material) carrying the fastener 208 is pushed distally through the outer tube 200 and over both the first portion 210 and the second portion 211 of the tension member 207. The outer tube 200 is pulled back from the uterine tissue and the crimping device 209 is pushed distally until its distal end protrudes from the outer tube 200 to approach or contact the tissue wall TW of the uterine tissue surrounding the tumor (as shown in fig. 7E). The tension member 207 is then tightened along its length with a selected tension to affect compression of the volumetric region VR to increase pressure within the tumor. The tightening occurs while the ductile material 208 is in place or even pushed against the tissue wall TW to oppose the pulling force and achieve tightening and compression of the volumetric region VR. Once the tension member 207 is tightened with the selected tension, the ductile material 208 is crimped over the first portion 210 and the second portion 211 of the tension member 207 using the crimping device 209, thereby securing the first portion 210 and the second portion 211 together and maintaining the desired tension in the tension member 207. Thus, tightening is maintained to achieve ischemia within the volumetric region VR and/or tumor and ultimately necrosis in most or all tissues of the tumor, as previously described.

Fig. 8A-8B schematically illustrate an exemplary scenario representing steps or stages of another method, which may differ in some respects from the steps shown in fig. 7A-7B. As previously discussed, in fig. 7A-7B, the stylet 205 is not initially coupled with the tension member 207, but rather is coupled with the exit opening EX after it has been formed and/or passed therethrough. Once coupled with the tension member 207, the stylet 205 pulls the tension member 207 along the channel 204, first through the outlet opening EX towards the inlet opening EO and finally through the inlet opening EO. In contrast, in fig. 8A-8B, the stylet 205 is initially coupled with the tension member 207 and advances (e.g., pulls) the tension member 207 in tandem therewith as the stylet 205 advances along the channel 204, first through the inlet opening EO toward and finally through the outlet opening EX (fig. 8A). Referring to fig. 8B, the end portion of the tension member 207 is captured by the snare 220 and pulled outside the body. In the illustrated embodiment, the snare 220 is movable through the second lumen of the elongate member. In particular, the elongate member comprises a needle portion, such as the first needle described previously, which extends distally relative to the secondary tube. The secondary tube defines a second lumen through which the snare and tension member 207 may pass.

Fig. 9A-9I schematically illustrate exemplary scenarios representing steps or stages of another illustrative method for treating a tumor. The depicted phase may be performed after a direct access is made (e.g., in a minimally invasive manner) from outside the body of the subject (patient) to the tumor (as shown, for example, in fig. 5A-5F). Minimally invasive access to the tumor can be created by transvaginal surgery, endoscopy, laparotomy, or laparoscopy. In fig. 9A, a device 300 for deploying one or more tension members, each in the form of a suture-use wire, is illustrated. Device 300 includes a straight central outer tube 301 and curved lateral outer tubes 302. The lateral outer tubes 302 are hingedly connected to lateral portions of the central outer tube 301 and are selectively manipulable between a lateral position in which their distal ends 303 are positioned laterally furthest away from the central outer tube 301 (e.g., as shown in fig. 9A) and a forward position in which their distal ends 303 are positioned distally furthest away from the central outer tube 301 (e.g., as shown in fig. 9C). Device 300 also includes a straight central inner needle 304 extending within central outer tube 301 and having a central needle distal end 305 that is selectively axially extendable or projectable (and then retractable) along and relative to central outer tube 301. Device 300 further includes a curved laterally inner needle 306 extending within lateral outer tube 302 and having a laterally inner needle distal end 307 that is selectively axially projectable (and then retractable) along and relative to lateral outer tube 302. Each of the central outer tube 301, the lateral outer tube 302, the central inner needle 304 and the lateral inner needle 306 may be actuated independently of each other by an operator, at least with the actuations related to the respective functions described above. The device 300 with each of its components 301, 302, 304 and 306 may also be actuated from its distal and/or proximal end, which may be located outside the body of the subject being treated (human patient), such as via a laparoscopic port provided through the abdominal wall.

Fig. 9A shows the apparatus 300 approaching a tissue wall TW of uterine tissue surrounding a tumor (fibroid) when the lateral outer tube 302 is in a lateral position and each of the central inner needle 304 and the lateral inner needle 306 are provided in a retracted configuration. In fig. 9B, the central outer tube 301 is pressed against the tissue wall TW above the tumor, and the central inner needle 304 is pushed into a protruding configuration such that it penetrates the tissue wall TW and extends completely across the tumor, with the distal end 305 of the central inner needle positioned beyond the tumor relative to the tissue wall TW. Upon penetrating tissue wall TW, central inner needle 304 forms an entrance opening EO at tissue wall TW into uterine tissue and/or directly into the tumor. In fig. 9C, lateral outer tube 302 is actuated into the forward position, thereby pressing against the lateral portion of uterine tissue wall TW that is lateral to the tumor, pushing it distally and laterally toward the tumor. In fig. 9D, the laterally inner needle 306 is pushed around the tumor perimeter into a convex configuration such that the laterally inner needle distal end 307 reaches the central inner needle distal end 305 in a manner that promotes interaction with the central inner needle distal end 305. Upon penetrating tissue wall TW, laterally inner needle 306 forms an exit opening EX into uterine tissue at tissue wall TW.

In fig. 9E, a tension member 308 configured as a suture-use wire is passed from outside the subject's body in a distal direction within the central inner needle 304 until it extends across the entire thickness of the tumor. A stylet 309 carrying a hook 310 at its distal end projects from the side towards the inner needle distal end 307 for capturing the tension member 308. A lateral opening 311 on the central inner needle distal end 305 allows the hook 310 to pass transversely through the lumen of the central inner needle 304 and interact directly with a tension member 308 disposed inside the lumen. In fig. 9F, the hook 310 is retracted while pulling the tension member 308, and the laterally inner needle 306 is also retracted into the laterally outer tube 302. In fig. 9G, lateral outer tube 302 is pulled into a lateral position, thereby pulling the second portion of tension member 308 further through outlet opening EX. In fig. 9H, the device 300 is withdrawn, holding only the tension member 308 in place such that it extends through the tumour, a first portion 312 of the tension member extending from the uterine tissue and optionally from the body of the subject via the inlet opening EO, and a second portion 313 of the tension member extending from the uterine tissue and optionally from the body of the subject via the outlet opening EX. Via laparoscopic access, the operator (optionally using the apparatus 300) tightens the tension member 308 and secures (e.g., by ligating) the first portion 312 and the second portion 313 of the tension member 308 in or out of the body, which maintains the taught tension member 308 at the selected tension (fig. 9I).

Note that in some cases, the fixation of different portions of the tension member may be achieved in vivo rather than ex vivo, as with other methods previously discussed (e.g., with respect to fig. 6A-8B). For example, certain suture tying and/or suture tightening mechanisms may be employed at the interior of the body, such as via a laparoscopic port.

Fig. 10A-10C schematically illustrate cross-sectional views of components of an example apparatus 400 having a suture passing mechanism configured for passing a tension member around a tissue mass. Fig. 11A-11D schematically illustrate scenarios representing steps or stages in various exemplary methods for using device 400. Fig. 10A shows a rigid outer tube 401 comprising a sharp outer tube tip 402 and an outer tube lumen 403 leading to an outer tube opening 404 formed as a lateral opening proximal to the outer tube tip 402. The outer tube 401 comprises a bevel configured with a beveled face 406 opposite a straight side 407 (relative to the longitudinal axis of the outer tube 401) enclosing an outer tube side opening 404. The outer tube uncovering mechanism 408 is provided with the outer tube 401 and is configured for fixing a selected uncovered length UL of the outer tube 401 relative to a tube cover 409 covering the remaining length of the outer tube 401 (as shown in fig. 11A). Tube cap 409 has a distal boundary 405 (e.g., outer diameter) that is substantially wider than the boundary (e.g., outer diameter) of outer tube 401, configured to resist penetration of outer tube 401 into soft tissue beyond a depth penetrable by uncovered length UL.

Fig. 10B shows an inner needle 410 in an unstressed relaxed length (in which no external or internal stress is applied in a manner sufficient to deform (at least not significantly and/or visually) its size and/or shape), comprising an elastic needle body 411 ending in a sharp (e.g., beveled, pointed, pierced) needle tip 412 and enclosing an inner needle lumen 413. Inner needle lumen 413 opens into inner needle opening 414 proximate needle tip 412. The inner needle 410 is configured to pass through the outer tube lumen 403 while in the straightened configuration due to its flexibility and constraining rigid boundary of the outer tube lumen 403 achieved by the surrounding walls of the outer tube 401 (as shown in fig. 11B). Once the inner needle 401 partially protrudes through the outer tube opening 404, the protruding portion 423 of the inner needle 401 is configured to flex itself (by its elastic nature) and regain a curved form, as shown in fig. 11C. When advanced in its curved form in soft tissue, the inner needle 410 is configured to pierce a curved channel around a target tissue mass by rotationally advancing through the soft tissue surrounding the tissue mass when pushed through the outer tube opening 404.

The apparatus 400 is configured to pass a tensioning member around a tissue mass (such as a fibroid), which may be of different size, shape and/or depth (e.g., relative to the surface of an internal body organ). Thus, in some cases, it may be advantageous to preset a penetration length (predetermined or from within a range of allowed selectively fixable lengths) taken from and equal to the uncovered length UL. This measured penetration of the outer tube 401 will allow the outer tube opening 404 to be positioned near the outer periphery of the target tissue mass so that the projecting portion 423 of the inner needle 410 can bend beyond and around and proximate to the distal boundary of the tissue mass. In some embodiments, the uncovered length UL is determined as a function of positioning the outer tube opening 404 proximate (e.g., near the middle of) a selected portion of the tissue mass. The predetermined uncovered length UL may be performed in advance using an analysis of invasive or non-invasive images.

Fig. 10C shows a stylet 420 in an unstressed, relaxed state, comprising: a stylet body 421 sized for passage through the inner needle lumen 413; and a stylet fixing member 422, optionally a wire forming a snare-like structure with the stylet body 421, configured for fixing a portion of the tension member to the stylet body 421. As shown in fig. 11D, the stylet 420 is advanced through the inner needle lumen 413 until the stylet stationary member 422 protrudes (fully or partially) from the inner needle opening 414. As will be described in detail below, the tension member may be secured to the stylet body 421 using the stylet securing member 422, and then may be withdrawn toward and/or into the outer tube lumen 403 (via the outer tube opening 404) by pulling the tension member with the stylet 420 (optionally along with the inner needle 410).

Fig. 12A to 12J schematically illustrate scenarios representing optional steps in an illustrative method for treating a tumor (shown as a tissue mass TM) located at least partially within an organ or body region BR of a subject's body. In various embodiments, the method comprises at least the steps of: volumetrically compressing the tumor or a portion thereof in the patient to increase pressure (optionally interstitial pressure) within the tumor above a threshold level sufficient to cause ischemia of the tumor; and maintaining the pressure above the threshold level for a period of time sufficient to allow at least a portion of the tumor to necrose due to ischemia.

The tumor is optionally circumscribed with at least one exogenous device (e.g., a tension member such as a surgical wire) relative to the patient, wherein volumetrically compressing the tumor and maintaining interstitial pressure is achieved via the at least one device. Each circumscribing step can include advancing at least one tensioning member around the tumor at an exterior of a prosthetic capsule surrounding the tumor. For example, a uterine fibroid may be surrounded by a potential space existing between uterine tissue and fibroid tissue, which may be referred to as the periarticular capsule space. In general, the term "potential space" may apply to a region between opposing surfaces of different types of tissue (e.g., tumor tissue and healthy uterine tissue). The uterine fibroid may be surrounded by a fibroid pseudo-envelope, which is a structure that separates the fibroid from the uterine tissue. Thus, the pseudocapsule may represent the outer limb of a uterine fibroid, and there may be a potential space between the pseudocapsule and the uterine tissue.

Optionally, the volumetric compression is performed along at least first and second compression lines that extend along different paths around the exterior surface of the tumor, optionally some or all of the paths being non-intersecting paths (see, e.g., fig. 3I) or alternatively at least some of the paths intersecting at an intersection (see, e.g., fig. 3H, where the intersection is shown at the center of the figure). The first compression line and the second compression line may intersect at a plurality of spaced apart intersection points. For example, in fig. 3H, due to symmetry, there may be a second intersection point of all tension members 10 at the opposite side of the volumetric region VR (e.g., on the non-visible side in fig. 3H). The threshold level of interstitial pressure may be no less than about 2 mmHg, optionally 4 mmHg, optionally in the range of 0.1 mmHg and 10 mmHg.

The method may include circumscribing the tumor with at least one tensioning member along a first path and along a second path different from the first path. The at least one tensioning member may comprise a single tensioning member looped around the tumor along a first path and a second path (see, e.g., fig. 3K). Optionally or alternatively, a first tensioning member and a second tensioning member are provided, wherein circumscribing along the first path comprises circumscribing the tumor with the first tensioning member along the first path, and wherein circumscribing along the second path comprises circumscribing the tumor with the second tensioning member along the second path (see, e.g., fig. 3H-3J).

In some illustrative embodiments, a method may comprise one or more of the following steps: passing a tension member within the organ between an inlet opening and an outlet opening (each opening at a surface of the organ) and around a volumetric region surrounding at least a portion of the tumor; tightening the tensioning member to cause a volumetric compression on the volumetric region, thereby directly increasing the pressure within the tumor; and continuously maintaining increased pressure to achieve ischemia in most or all tissues of the tumor.

The tumour treated is optionally a uterine fibroid and may be one of transmural, serosal or submucosal with respect to the organ in which it resides. Optionally, at least a portion of the tumor is located between walls within the organ, and wherein passing the tension member within the organ comprises passing the tension member through the inter-wall portion of the organ. Passing the tensioning member through the interwall portion of the organ may include passing the tensioning member around at least a portion of an interwall tumor located within the organ. In some such scenarios, passing the tension member within the organ may include passing the tension member only through an interwall portion of the organ and/or tumor between the inlet opening and the outlet opening.

To reach the surface of an organ and treat a tumor, a surgical pathway to the organ may first be created from outside the body, which may be created, for example, using minimally invasive techniques or by open surgery. At least one of the basic method steps (threading, tightening and maintaining) may be performed via a surgical pathway.

The inlet opening may be located at a first location on or adjacent the tumour and the outlet opening may be located at a second location on or adjacent the tumour, the second location being spaced from the first location such that the tumour is located between the inlet opening and the outlet opening.

Prior to passing the tension member, a channel may be formed around the volumetric region between the inlet opening and the outlet opening, optionally also forming the inlet opening and the outlet opening, such that passing may be performed predominantly or completely within the channel, optionally by pulling the tension member towards the inlet opening via the outlet opening. The channel may be formed using device 400 or any other applicable device or mechanism. For example, an outer tube may be used to form an access opening and be positioned through the access opening into an organ to access a tumor. A curved needle may then be advanced through the lumen of the outer tube around the volumetric region.

The volume portion may be predetermined by the user (practitioner, physician, surgeon, etc.) and the passing of the tension member may be performed in a tight fit and around the volume portion. Determining the volume portion may comprise determining an entry point to and an exit point from the organ relative to the tumor, and possibly also determining a particular plane across the tumor and the entry and exit points. Passing the tension member may be along a predetermined path line between the inlet opening and the outlet opening. The access wire optionally protrudes across one or more blood vessels feeding the tumor such that tightening of the tension member directly causes occlusion of the blood vessels, such as previously discussed.

Passing the tensioning member may comprise wrapping more than half of the circumferential portion of the tumour with the tensioning member and/or it may comprise wrapping the tensioning member or a plurality of additional tensioning members along separate paths and/or planes around the volumetric region. Passing the tension member may further include deploying a plurality of windings (wrapping) around the additional volumetric region, with the additional volumetric region surrounding at least another portion of the tumor. The volumetric region optionally surrounds a majority or all of the tumor volume.

In various embodiments, to achieve a selected tension, optionally a predetermined tension, tightening of the tension member is performed. The tension applied to the tension member and/or the pressure within the tumour may be measured at least during tightening of the tension member.

Tightening of the tension member may be performed using a tightening device that may optionally be removed from the body before and/or during the stage of maintaining increased pressure within the tumor. As pressure increases, the pressure within the tumor may be higher than the capillary blood pressure of the blood vessels supplying the tumor, thereby reducing or preventing the transfer of oxygenated blood to the tumor tissue and causing gradual ischemia. Optionally, the volume compression is continuously maintained at least until necrosis is achieved in most or all tissues of the tumor. Optionally, the tension member and the plurality of additional tension members are tightened to collectively apply a radial compression force toward the center of the tumor.

Tightening the tension member may include or may be followed by the steps of: a first portion of the tension member projecting from the inlet opening is secured to a second portion of the tension member projecting from the outlet opening to facilitate maintaining the increased pressure. Securing the portions of the tension member together optionally includes: a fastener is coupled to the first and second portions of the tension member to maintain the tension member in a tightened state. The fastener optionally includes a ductile material, and securing the tension member then includes crimping the fastener around the first and second portions of the tension member. The step of securing portions of the tensioning member is optionally performed outside the boundaries of the organ, optionally from outside the body through a surgical access, and may be performed using a cinching device or a separate device.

The tension member optionally comprises a flexible strip or wire (such as a suture-grade wire), and may be formed from at least one of an implant-grade metal alloy, an implant-grade polymer, an implant-grade textile, and a biodegradable material. In certain embodiments, the tension member is configured with a yield strength or maximum tension of at least 25N (newtons) so as not to prevent failure during tumor compression. Optionally, the tensioning member is configured to yield above about 80 newtons or about 100N (newtons), after which it may cause a cut in the organ tissue caused by the tensioning member pressing against the tumor. Optionally, the tensioning member is formed as a biodegradable suture-use wire and is configured to yield under a tensioning force of less than 25N (newtons) after ischemia or necrosis of the tumor tissue (e.g., after weeks or months).

With further reference to fig. 12A-12G, various stages of an illustrative method of passing a tension member configured as a wire (e.g., suture) 430 around a tumor TM within an organ ORG are demonstrated. Fig. 12H-12J demonstrate stages of an illustrative method of compressing a tumor TM above a selected pressure and maintaining the compression by: one or more of the tension members 430 are tightened with one or more wraps around the tumor TM and secure the first and second portions of the tension members 430 together while being tightened under the tightening force. Passing a tension member around a tumor TM may be performed using a suture passing mechanism, such as device 400. Performing the tightening (and/or compression) and securing (and/or maintaining) may be performed using separate mechanisms within the same device or via separate devices, optionally within a device (e.g., device 400) that may be suitable for suture threading.

Fig. 12A illustrates an exemplary scenario in which at least two surgical (e.g., minimally invasive or laparoscopic) access openings O1 and O2 are formed to the abdominal wall AW for forming independent channels into and from the abdominal cavity AC through to the outer surface OS of the organ ORG (e.g., uterus). Either of the surgical access openings O1 and O2 may be percutaneous incisions or fixed channels maintained by an artifact, such as a trocar or cannula.

As an optional preliminary step, the user (surgeon, practitioner, etc.) may determine a desired orientation of the tension member relative to the tumor TM passing within the organ ORG. Such calculated, selected and/or predetermined orientations may be spatial or two-dimensional. The user may determine at least one volumetric region VR encompassing at least a portion of the tumor TM. Alternatively, alternatively or additionally, the user determines a plane across or through the tumor TM on which an entry point to and exit point from the organ ORG will be made. Optionally, a penetration depth D is defined, which is obtained from an entry point P1 at the surface OS with respect to the boundary of the tumor TM.

The suture is then placed into use through a mechanism (optionally part of device 400). In some cases, by appropriately withdrawing the tube cap 409 (as described above), a selected uncovered length UL of the outer tube 401 is first set or fixed, which may be substantially equal to the penetration depth D. The device 400 is then passed through the first laparoscopic opening O1, and the device 400 is then pressed with the sharp outer tube tip 402 against the surface OS in the selected direction until penetrating the soft tissue of the organ ORG proximal to the tumor TM (fig. 12B). By doing so, tip 402 forms an entry point P1 and a first segment of the surgical pathway within organ ORG around tumor TM and/or volume portion VR. The device 400 is pushed distally until the outer tube tip 402 reaches a predefined penetration depth D or possibly slightly exceeds it, or until the outer tube opening 404 is positioned a selected distance (e.g., a selected proximal distance) from the distal boundary of the tumor TM. For example, in some cases, opening 404 may desirably be positioned at a depth corresponding to about the middle of the tumor TM (i.e., a distance substantially equal to the radius of the tumor TM, such as spaced apart from the distal boundary of the tumor). In some embodiments, the device 400 (or in particular, the outer tube 401 and/or the inner needle 410) has a size selected from a plurality of sizes such that the length between the outer tube opening 404 and the outer tube tip 402 is a size of about the tumor TM radius. In such an embodiment, the penetration depth D would be determined such that if the outer tube tip 402 were to approach the distal boundary of the tumor TM, the outer tube opening 404 would also be near the middle of the tumor TM.

In other words, in some cases, multiple inner needles 410 may be provided. Each needle 410 may have a pre-curved region with a length and/or radius of curvature that is different from the length and/or radius of curvature of the remaining options. The user may select one inner needle 410 from a plurality of inner needles available that will form a channel of a desired shape, size and/or orientation around the tumor. In some cases, an outer needle 401 is provided separate from one or more of the inner needles 410. In other cases, the outer needle or tube 401 and the plurality of inner needles 410 are provided together (e.g., in an integral kit).

As shown in fig. 12C, inner needle 410 may then be passed through outer tube lumen 413 at a length of travel sufficient to extend projecting portion 423 through outer tube opening 404 at a selected projecting length. Thus, by pushing the inner needle 410 through the outer tube opening 404, the surgical channel formed in the organ ORG extends around the volumetric region VR and/or the tumor TM along the span of the bulge 423 in a curved section, which is pierced with the needle tip 412. As described above, the convex portion 423 is naturally flexed from the straightened shape to regain the previously formed curved form; and the curved portion may be advanced along a curved path through the soft tissue surrounding the tumor TM in order to facilitate the formation of a curved channel segment (e.g., via piercing the tissue).

After forming the curved portion of the path via inner needle 410, stylet 420 (which optionally may be preloaded within inner needle 410) is advanced through inner needle lumen 413 and out of inner needle opening 414 until fixation member 422 portion exits organ ORG at exit point P2, which may be spaced from entry point P1 relative to tumor TM (e.g., located opposite relative to entry point P1) (fig. 12D). In other words, entry point P1 and exit point P2 may be at opposite sides of the tumor along the surface of the organ (e.g., uterus). As described above, the location of exit point P2 may be predetermined or at least selected or determined in advance in relation to the distance and orientation of inner needle tip 412 relative to inner body region outer surface OS. In some cases, it may be desirable for exit point P2 to be in the range of 2 cm to 5 cm from entry point P1, in order to: for example, keeping the two points P1, P2 within the user's visible range (e.g., via separate channels or surgical openings using an endoscope or camera positioned in the abdominal cavity AC); in some cases, sufficiently far from adjacent organs that could be injured if inadvertently penetrated; and/or effectively tension both ends of the tension member 430 around the tumor TM, which ends of the tension member 430 will eventually emerge from points P1 and P2, as shown in fig. 12G.

In certain embodiments, the tension member 430 is inserted into the abdominal cavity AC through the first surgical opening O1 or the second surgical opening O2 (in this example, the first opening O1 is alongside the device 400, through the device 400, or with the device 400), as shown in fig. 12E. A portion of the tension member 430 is then passed through the lumen of the fixation member 422, optionally using a surgical tool (such as a surgical grasper) operable via the second opening O2. Accordingly, the tension member 430 can be coupled or secured to the stylet body 421 and drawn toward and/or into the inner needle lumen 413 and/or the outer tube lumen 403 by pulling the stylet 420 and the tension member 430 secured thereto (fig. 12F). In some cases, as the fixation member 422 is drawn into the lumen of the tube 401 and/or the inner needle 410, the grip of the fixation member 422 on the tension member 430 may be increased or enhanced because the loop formed thereby may be resiliently compressed as it enters or passes through its lumen.

The device 400 is then pulled out of the organ ORG while dragging the captured tension members 430, and the device 400 is then removed from the patient's body. As a result, the tension member 430 may be kept extending around the volumetric region VR and/or the tumor TM such that one portion 431 of the tension member 430 extends from the entry point P1, through the abdominal cavity AC, and out of the patient's body, and another portion 432 of the tension member 430 extends from the exit point P2, through the abdominal cavity AC, and out of the patient's body (fig. 12G). For the next steps of the method, which include tightening (and/or pressing the tumor) and fixing (and/or maintaining the tumor pressing) the tension member 430, the two parts 431 and 432 of the tension member 430 can be further manipulated from outside the body.

Optionally, to perform the tightening and securing of the tension member 430, the device 400 is withdrawn and replaced with a single device or a plurality of separate devices that include a tightening mechanism for tightening the tension member 430 and a securing mechanism for securing (e.g., fastening) the first and second portions 431, 432 of the tension member 430 together for maintaining a selected tightening force therein and therethrough to continuously compress the volumetric region VR and/or the tumor TM.

As shown in fig. 12H, the tensioning member 430 is tightened around the volumetric region VR and the tumor TM by applying a selected tightening force F (optionally applied from outside the patient's body). Force F may be applied by one or both of portions 431 and 432 of tension member 430. In some embodiments, before, during, or after the selected tightening force F is reached, fasteners 433 are applied on both ends and passed over portions 431 and 432 of tension member 430 into abdominal cavity AC until positioned proximate entry point P1 and exit point P2 (as shown in fig. 12I). By pushing fastener 433 towards organ ORG and applying tension force F to tension member 430, a compressive force is applied to volumetric region VR and tumor TM, which increases the pressure in the tumor and optionally compresses the tumor TM and/or its surrounding soft tissue. Once a selected pressure is reached in the tumor TM (e.g., correlated to the force F magnitude or measured directly from the tumor), the fasteners 433 can be crimped onto the first and second portions 431, 432 of the tension member 430 (fig. 12J), thereby maintaining the compressive force applied to the tumor TM even when the tension member 430 is released. The remaining length of suture 430 may be trimmed and removed as needed or desired. In some cases, suture 430 may be made of a biodegradable or bioresorbable material and remain implanted indefinitely.

In some cases, the fastener 433 may be formed of a non-bioresorbable material and may likewise remain implanted indefinitely, for example may be left in the patient after the surgical access site has been closed. In some cases, the non-bioresorbable fastener 433 may remain in the patient's body in one piece for longer than the tension member 430. Some or all of the steps may be repeated for the same fibroid, and each repetition may be performed around the same volumetric region but in a different planar or spatial orientation and/or via different entry and exit points using different implant devices (tension members). In other or additional cases, some or all of the steps may be repeated as well for one or more additional fibroids.

A plurality of tensioning members circumscribing the tumor TM, each disposed along a different tumor-traversing plane (e.g., as shown in fig. 3A-3K) and maintained tightened at a selected magnitude, can cumulatively induce a selected volume (e.g., spherical) compression on the tumor TM, thereby increasing pressure therein (e.g., uniformly increasing pressure) to a degree (e.g., in vivo or in vitro) known or tested to induce ischemia. In some embodiments, the increased pressure increases the local interstitial fluid pressure in the tumor TM and/or volumetric region VR to a degree sufficient to inhibit or stop interstitial fluid flow to the tumor and surrounding host tissue. In some embodiments, the increased pressure in the tumor TM and/or volumetric region VR is sufficient to inhibit or stop tissue oxygenation from the associated vasculature (blood vasculature) of the tumor and surrounding host tissue. In some embodiments, the tensioning member(s) is biodegradable and is configured to yield autonomously and then dissolve after a period of time sufficient for the organ and/or tumoral tissue to spontaneously undergo necrosis caused by continued ischemia due to compression effected by the tightened tensioning member(s).

Reference is now made to the following: fig. 13A-13D, which illustrate views of a device 500 for compressing a tumor in an organ of a body of a subject (e.g., a tumor TM in an organ ORG such as that shown in fig. 12G); and FIG. 13E, which shows a block diagram representing an exemplary design implementation of device 500. Apparatus 500 includes an elongated body 501 configured for reaching a surface OS of an organ ORG proximate a tumor TM via a surgical pathway (e.g., surgical opening O1) formed in a subject's body. Alternatively, the elongate body 501, or a portion thereof, may reach the organ surface OS via the natural body orifice at least along some of its channels (e.g., via transcervical access). The apparatus 500 includes a tightening mechanism 502 configured to tighten a tension member (e.g., tension member 430) extending around a volumetric portion of a tumor (e.g., volumetric portion VR shown in fig. 12A), such as when a first portion 431 of the tension member protrudes from the inlet opening P1 and a second portion 432 of the tension member protrudes from the outlet opening P2. In some embodiments, it is desirable to dispose the free end of the tension member 430 outside of the patient's body, and the first and second portions 431, 432 extend from the inlet and outlet openings P1, P2, respectively, and extend through the surgical opening O1, as shown in fig. 12G. In some embodiments, the tightening mechanism 502 is configured to limit manual use to a gradual, continuous, or discrete increase in the tightening force until a selected tightening force is reached.

The apparatus 500 further comprises a securing mechanism 503 configured for securing the first portion 431 to the second portion 432 of the tension member 430 via the elongated body 501 proximate to a surface of the organ for maintaining the tension member 430 in a tightened state even after the tightening mechanism 502 has stopped applying force to the tension member 430 and/or has disengaged from the tension member 430. The apparatus 500 further includes a force manipulator unit 513 having a manually operable trigger 515 pivotally connected to the apparatus 500 (as shown in fig. 13C) and coupled with a trigger gear 516 for selectively transmitting force to either of the tightening mechanism 502 and the securing mechanism 503 through a gear train architecture. Trigger gear 516 is optionally connected to tightening mechanism 502 by trigger one-way device 517, thus transmitting force only when trigger 515 is in a pressing motion and not when it is withdrawn upon release (e.g., rebounds) during a trigger press cycle that includes a pressing followed by a withdrawing trigger 515.

The force manipulator unit 513 may operate only one of the tightening mechanism 502 and the fixing mechanism 503 at a time. This allows the same trigger and other associated components to be used for operating both mechanisms, but also for structurally maintaining functional independence between tightening mechanism 502 and securing mechanism 503. This is achieved by using a clutch member 518 which can be manually operated using a selector switch 521, and which clutch member 518 can be applied to selectively engage a trigger gear 516 of the force manipulator unit 513 with a tension force transmitting gear 519 for transmitting force to the tightening mechanism 502, or to be selectively disengaged therefrom so as to stop any such force transfer thereto. Further, the force manipulator unit 513 may transmit force to operate the securing mechanism 503 when the trigger 515 is pressed only when the clutch member 518 is disengaged from the tension transmitting gear 519, and prevent the force manipulator unit 513 from transmitting force to operate the securing mechanism 503 when the trigger 515 is pressed when the clutch member 518 is engaged with the tension transmitting gear 519.

As presented in fig. 13E, the selection switch 521 has two preset positions selectable by the user: position (a) for connecting the force manipulator unit 513 to the tightening mechanism 502, and position (b) for connecting the force manipulator unit 513 to the fixing mechanism 503. When the selector switch 521 is set to position (a), the clutch member 518 is switched into engagement with the tension force transmitting gear 519 and with the trigger gear 516 (via the trigger one-way device 517) so that the trigger gear 516 can transmit force to operate the tightening mechanism 502, but cannot transmit force to operate the fixing mechanism. When the selector switch 521 is set to position (b), the clutch member 518 is disengaged from the tension force transmitting gear 519 and/or from the trigger gear 516, and the trigger gear 516 may transmit force to operate the fixing mechanism 503 but may not transmit force to operate the tightening mechanism 502.

The possibility of preventing (in position (a)) or promoting (in position (b)) the force transfer from the trigger force manipulator unit 513 to the fixing mechanism 503 can be achieved by changing the range of motion of the trigger 515 and the trigger gear 516. Fig. 13F to 13G demonstrate a first range of motion ROM-1 in the trigger 515 when the selector switch 521 is set to position (a), and fig. 13H to 13I demonstrate a second range of motion ROM-2, which is greater than the first range of motion ROM-1, when the selector switch 521 is set to position (b). As shown in the figure, when the trigger 515 is pressed to the entire range of the first movement range ROM-1 (as shown in fig. 13G), the pressing part 522 of the trigger gear 516 cannot reach the force receiving part 523 of the fixing mechanism 503, and therefore the force manipulator unit 513 cannot transmit the force to the fixing mechanism 503 when the selection switch 521 is set to the position (a). However, when the selector switch 521 is set to the position (b), the pressing portion 522 is reached, and then the pressing portion presses against the force receiving portion 523 when the trigger 515 is pressed to the entire range of the second movement range ROM-2 and thus transmits the force to operate the fixing mechanism 503 (as shown in fig. 13I).

Exemplary tightening mechanism

The tightening mechanism 502 includes: a first pulling member 504 configured for anchoring to and selectively pulling the first portion 431; and a second pulling member 505 configured for anchoring to and selectively pulling the second portion 432 of the tension member 430. Each of the first and second pulling members 504, 505 is configured as a spool and includes a spool member 506 upon which a corresponding end portion of a tension member 430 formed as a flexible wire (e.g., suture, film, or wire) may be wound to a selected degree (e.g., a selected length of wound portion or a selected tension applied to the tension member, for example). The remaining unwound length of the tension member 430 may extend from one or both spool members 506 through rollers 508. For example, when the apparatus 500 is properly oriented as shown in fig. 13A, the roller 508 is positioned horizontally between the elongate body 501 (most distal) and the spool member 506 (most proximal), while the elongate body 501 is positioned vertically between the roller 508 (most superior/inferior) and the spool member 506 (least inferior/inferior). The roller 508 is configured to rotate as the tension member 430 moves along its axial direction, such as when the tension member 430 is pulled or released by the spool member(s) 506. Optionally and alternatively, the rollers 508 are stationary and have a smooth outer surface for allowing the tension members 430 to slide therealong unimpeded.

The apparatus 500 comprises a measuring unit 509 configured for indicating a measured magnitude when providing the tension member around the volume portion VR and tightening the tension member 430 by the tightening mechanism 502. The measured magnitude may relate to any of the tension, compression change of the volume portion VR, and/or pressure change within the tumor TM. The measurement unit 509 comprises a scale 510 having a series of values representing absolute or relative magnitudes. The measurement unit 509 is operated by a pulley unit 507 comprising a pulley arm 511 extending from the roller 508 and pivotally connected to a rear (distal) end of the device 500, which is fixed relative to the elongate member 501. A number 512 projects from the free end of the pulley arm 511 and is movable within the scale 510 between a lower limit and an upper limit of a range of values of the pointing scale 510. The measurement unit 509 is configured such that a tensioning force applied by one or both spool members 506 to the tension member 430 will, through the roller 508, take up a comparable pressing force on the pulley arm 511 that will force the number 512 to be positioned next to a scale value that approximately indicates the measured magnitude.

When the force manipulator unit 513 is connected to the tensioning mechanism 502 and can transmit a force to operate it (as described above), a pressing motion of the trigger 515 will cause the first and/or second puller members 504, 505 to apply a tensioning force to the tension member 430, e.g. so as to force it into a contracted state sufficient to compress a volume portion and/or increase the pressure within a tumor. When the force manipulator 513 is functionally and/or structurally connected to the first puller member 504 and/or the second puller member 505, it is configured to incrementally increase the tension of the tension member 430 along at least one cycle of the pressing motion of the trigger 515. Since the trigger gear 516 is connected to the tightening mechanism 502 via the trigger check 517, pressing the trigger 515 will cause a tensioning force to develop in the tension member 430, but withdrawing (releasing) the trigger 515 will have no effect on the applied tensioning force. This mechanism facilitates maintenance of the tensioning force (achieved by the last trigger press motion) when the trigger 515 is withdrawn after each cycle of trigger press motion, at least until the selected tensioning force is reached.

Fig. 14A-14C illustrate views of the proximal portion of the device 500, which represent several scenarios of operating the tensioning mechanism 502. The apparatus 500 is equipped with a tension member 430 that is partially wound around a spool member 506 with an unwound length of the tension member extending distally therefrom in the patient's body and between the spool member 506 through rollers 508 around the volumetric region VR and tumor TM along the longitudinal body 501 (e.g., as shown in fig. 12H). Fig. 14A schematically illustrates the tension member 430 in a relaxed state, and the operator must press (squeeze) on the trigger 515 for tightening the tension member 430 one or several times (as shown in fig. 14B), and then optionally continue to press the trigger 515 one or several times until a selected amount is reached. Fig. 14C provides an enlarged view of the scale 510 with an exemplary relative magnitude of the selected tension force that implies about 80% of the maximum allowable tension force.

A tensioning force may be applied to the tension member 430 by pulling the first and second portions 431 and 432 together (e.g., as shown in fig. 15A), or that end of the tension member 430 (e.g., the first portion 431) may be first secured relative to a pulling member anchored to the second end of the tension member 430 (e.g., the second pulling member 505), for example as shown in fig. 15B and 15C. In fig. 15B, the free end of the tension member 430 extending from the first portion 431 is secured to the apparatus 500 around the static knob 514; thus, by pulling the second portion 432 with the second pull member 505, a tension force will be gradually created between the second pull member 505 and the static knob 514. In fig. 15C, the free end of the tension member 430 extending from the first portion 431 is anchored to a tubular fastener 433, such as by forming a knot 434 that is larger in size than the lumen of the fastener 433; thus, by pulling the second portion 432 with the second pulling member 505, the knot 434 will be displaced to press against the fastener 433, thereby preventing the first portion 431 from being further displaced in the pulling direction, and then creating a tensioning force that can force the tension member 430 to tighten between the second pulling member 505 and the knot 434 to a selected degree.

Fig. 16A shows a block diagram of an exemplary design embodiment of a tightening mechanism 502, which may be implemented in device 500. Fig. 16B illustrates an exemplary gear train embodiment of the take-up mechanism 502, and fig. 16C is an exploded view of the components shown in fig. 16B. As previously described, the tightening mechanism 502 includes a tension force transmitting gear 519 configured to reciprocally transmit force from the force manipulator unit 513 to the first and second pull members 504, 505. In order to apply a consistent tension force along the tension member 430 implanted in the organ ORG around the tumor TM, the first puller member 504 and the second puller member 505 are functionally and/or structurally independent of each other in at least one of rotational speed and pulling force.

This independence between the pulling members 504 and 505 is achieved, for example, by using a differential gear unit 538 comprising a differential gear 524 which is rotatable with the tension force transmitting gear 519 and reciprocally engaged with a first pulling gear 528 fixedly connected to the first pulling member 504 and with a second pulling gear 527 fixedly connected to the second pulling member 505. The differential gear 524 is reciprocally engaged with a first bevel gear 526 fixedly connected to a first pull gear 528 and with a second bevel gear 525 fixedly connected to a second pull gear 527.

The rotation of the tension force transmitting gear 519 transmits a force to rotate the entire differential gear unit 538, which causes the rotation of the first and/or second pull gear 528, 527 by halving the force transmitted thereto by the differential gear 524 between the first and second pull gears 528, 527. Each of the first and second pull gears 528, 527 are connected to a separate pull unidirectional device 529. When the tension force is increased in one of these portions of the tension member 430 relative to the other portion, and/or when the increased tension force exceeds a certain magnitude (e.g., has a predetermined value), the pull one-way device 529 in the respective pull gear 528 or 529 resists this relative increase in tension force, locking the respective gear from rotating in the direction of the tension force. This will cause a differential relative rotation between the first and second traction gears 528, 527. While one pull gear 528 or 529 is locked, only the other pull gear will continue to rotate with the differential gear 524 for increasing the tension in the other, slack portion of the tension member 430 until a substantially uniform tension is generated in both portions of the tension member 430 (e.g., in the first portion 431 and the second portion 432, and/or between these portions).

In this exemplary design embodiment of tightening mechanism 502, when force manipulator unit 513 is continuously or repeatedly applied to tighten tension member 430 until the selected tension is reached, tightening mechanism 502 is configured to cause the following exemplary sequence:

(1) the first and second portions 431, 432 of the tension member 430 are pulled back and forth (together) from a relaxed state by applying the first and second pulling members 504, 505 until one of the first and second portions (e.g., the first portion 431) reaches a taut state (no longer slack),

(2) (e.g., by applying the second pulling member 505) to pull the slack portion (e.g., the second portion 432) of the tension member 430 until it also reaches substantially the same taut state, an

(3) By applying the first and second pulling members 504, 505, the first and second portions 431, 432 are pulled reciprocally from a taut state of each until a selected tension is reached in the tension member.

Exemplary securing mechanism

As described above, the securing mechanism is configured for applying a fastener (e.g., fastener 433) to secure the first portion 431 to the second portion 432 of the tension member 430, thereby maintaining the tension member in the selected tightened state for an extended period of time. The extended period of time may be sufficient to cause ischemia and/or necrosis in most or all tissues of the tumor (e.g., tumor TM), during which the volume portion VR is continuously compressed by the tension member 430 and/or the tumor is forced to increase the pressure therein. Fig. 17A-17B illustrate views of the proximal portion of the device 500, which represent several scenarios of operating the securing mechanism 503. Fig. 17C shows a cross-sectional view of a fastener 433 crimped around the first portion 431 and the second portion 432 of the tension member 430. Fig. 18A-18D illustrate cross-sectional views of the distal portion of the device 500 showing several scenarios for crimping the fastener 433 by applying the securing mechanism 503.

In some embodiments, the apparatus 500 is configured to work with fasteners (e.g., fastener 433) that include ductile materials and are readily provided in a plastically deformable state, and the securing mechanism 503 is configured to crimp the fasteners around the first and second portions 431, 432 of the tension member 430. The fastener 433 includes a tubular fastener body 435 that is sized to allow two or more portions of the tension member 430 to pass therethrough. Crimping is facilitated when securing mechanism 503 is applied to compress and/or bend a portion 436 of fastener body 435 thereby securing first portion 431 and second portion 432 to portion 436.

As shown, the elongate body 501 includes a barrel 530 and an anvil 531 disposed at a distal end 532 of the barrel 530. The securing mechanism 503 includes a hammer head 533 that is slidable within a barrel 530 along a longitudinal axis of the barrel. The anvil 531 includes an anvil lumen 534 sized to receive the fastener body 435 therein. A longitudinal axis Y of the anvil lumen 534 is angled relative to the longitudinal axis X of the barrel 530, optionally enclosing an angle of about 45 degrees therebetween. When applied to crimp the fastener 433, when the selector switch 521 is set at position (B) for allowing the force manipulator unit 513 to transmit force to the securing mechanism 503 and the trigger 515 is pressed to the full extent (e.g., as shown in fig. 17B), the securing mechanism 503 is configured to force the hammer head 533 to press the portion 436 of the fastener body 435 against the anvil 531 for pressing and/or bending the portion 436. When a force receiving portion 523 of the fixing mechanism 503 (as shown in fig. 13H and 13I) is pressed by a pressing portion 522 of the trigger gear 516, the travel length of the hammer 533 in the cylinder 530 is acquired from the axial movement of the force receiving portion.

In some embodiments, a positioning spring 535 is disposed in the barrel 530 proximal to the hammer 533 and is configured to force the hammer 533 into a nominal position (shown in fig. 18A) such that the hammer 533 protrudes into the anvil lumen 534 in the absence of fasteners inside the anvil lumen 534. And is configured to retract when the fastener body is fully received within the anvil lumen. When the fastener (e.g., fastener 433) is placed with its fastener body 435 fully received in the anvil lumen 534, it forces the hammer head 533 to retract (fig. 18B). This retraction of the hammer 533 also forces the positioning spring 535 to preload under a preload force sufficient to effect anchoring of the fastener body 435 to the anvil 531. Upon actuation of the securing mechanism 503, as shown in fig. 18C, the hammer head 533 is forced to press and bend the fastener body 435 at the portion 436 thereof.

In addition to and in the alternative to using a positioning spring (e.g., positioning spring 535) to anchor the fastener body 435 to the anvil 531, other means may be used to hold the pre-crimped fastener until its crimping (by compressing and/or bending the portion 436). Fig. 19A-19B illustrate isometric views of the front (distal) portion of the elongated body 501 of the apparatus with barrel 530 and anvil 531, where fig. 19A shows the anvil 531 absent the pre-crimped fastener and fig. 19B shows the anvil 531 of the body fully receiving the fastener 433. A "C" shaped resilient member 537 is shown secured to the outer surface of the anvil 531 about a lower opening into the anvil lumen 534. The resilient member 537 is configured to press radially inward against an outer surface of a portion of the fastener body 435 when received in the anvil lumen 534, thereby anchoring the fastener 433 to the anvil 531. In some embodiments, the resilient member 537 is configured to snap lock to a portion of the fastener 433. Additionally or alternatively, the resilient member 537 may enclose a minimum diameter that is slightly less than the diameter of the fastener body 435, such that when the fastener 433 is passed through the lumen enclosed by the resilient member 537, the fastener body 435 will force the resilient member 537 to expand (e.g., by rapidly moving an end portion of the resilient member 537 outward (shoft)), and this may create a pre-load force that is sufficient to affect the anchoring of the fastener body 435 to the anvil 531.

The securing mechanism 503 optionally includes a retraction spring 536 configured to force the hammer 533 to retract and disengage from the compressed and curved portion 436 of the fastener body 435 immediately after crimping the fastener (fig. 18D). Alternatively, the retraction spring 536 is not configured to retract the hammer 533 after crimping the fastener, and optionally, it may be configured to balance and/or counteract movement of the hammer 533 captured from the positioning spring 535, such as for improved control of anchoring to a pre-crimped fastener. In some embodiments, the retraction spring 536 is instead located proximal to the hammer 533 and/or the positioning spring 535 and/or the barrel 530.

Exemplary System

Referring now to fig. 20, an exemplary system 550 is schematically illustrated that includes (at least) tightening mechanism 502, securing mechanism 503, and tension member passing mechanism 551. The system 550 may also include a force manipulator unit 513 configured to selectively and independently operate either of the tightening mechanism 502 and the securing mechanism 503 and optionally also the tension member passing mechanism 551. The tension member passing mechanism 551 is similar or identical in function and/or structure to the apparatus 400, and is configured for passing a tension member (e.g., tension member 430) around a tumor (e.g., tumor TM) in an organ of a subject's body (e.g., as shown in fig. 12A). Similar to the device 400, it includes (at least) an outer tube 401, a curved inner needle 410, and a stylet 420 (e.g., as shown in fig. 10A-10C). The tension member passing mechanism 551 is configured for affecting the organ ORG from the proximal end 553 of the elongate body 501 via the distal end 552 of the elongate body 501, for forming an inlet opening P1 and an outlet opening P2 at the surface OS of the organ ORG and for forming a surgical passage between the inlet opening and the outlet opening about a predetermined volume portion VR of at least a portion of the organ surrounding the tumor TM in a close-fitting manner (e.g., the surgical passage is similar or identical to the surgical passage 204 shown in fig. 7A). The tension member passing mechanism 551 is further configured for extending the tension member 430 around the volume portion VR, resulting in a situation in which the first portion 431 of the tension member 430 protrudes from the organ ORG via the inlet opening P1 and the second portion 432 of the tension member 430 protrudes from the organ ORG via the outlet opening P2 (e.g., as shown in fig. 12G).

Example kit

Fig. 21 schematically illustrates an example kit 560 including device 400 having a tension member passing mechanism and device 500 having a tightening mechanism 502 and a securing mechanism 503. In some embodiments, the kit 560 further includes one or more fasteners that are the same as or similar to the fasteners 433, in one or more sizes and/or in several dimensional variations.

Exemplary robot System

Fig. 22 schematically illustrates an exemplary robotic system 570 including a tightening mechanism 502, a securing mechanism 503, and optionally also a tension member passing mechanism 551. Optionally, the robotic system 570 further comprises a force manipulator unit (similar or identical in function and/or structure to the force manipulator unit 513) that is selectively connectable to a power source 571 via a computerized controller 572. Optionally, some or all of the tightening mechanism 502, securing mechanism 503, tension member pass-through mechanism 551, and force manipulator unit 513 are housed and operated from within a robotic arm end effector 573 that is connected to a robotic arm 574. Optionally, the robotic arm end effector 573 and some or all of the mechanisms 502, 503, and 551 are operatively connected to a bed unit 575 that can be controlled by the robotic system 570 and/or provide information and/or feedback signals to perform automated and/or telesurgery using any of the mechanisms 502, 503, and 551.

In some embodiments, the computerized controller 572 controls some or all of the functionality of the mechanisms 502, 503, and/or 551. Optionally, the tightening mechanism 502 is configured to facilitate presetting the selected tightening force and automatically cause the force manipulator unit to apply the selected tightening force. Optionally, the tightening mechanism 502 is configured to prevent tightening of the tension member 430 beyond a selected tension force. Optionally, the tightening mechanism 502 is configured for applying a force manipulator unit 513 to automatically increase the tension force transferred to the tension member 430 gradually, continuously or discretely until a selected tension force is reached.

Examples of the invention

The following are various illustrative examples, each of which is a separate embodiment. The present disclosure further includes all permutations of the following "independent" examples and "dependent" examples thereof. Moreover, additional embodiments that can be taken from the following independent and dependent examples are also expressly incorporated into this written description.

Example 1

A method for treating a tumor at least partially within an organ of a subject's body can comprise: passing a tension member within the organ between an inlet opening and an outlet opening (each opening at a surface of the organ) and around a predetermined volumetric region surrounding at least a portion of the tumor in a close-fitting manner; tightening the tensioning member to cause compression of the volumetric region, thereby directly increasing the pressure within the tumor; and maintaining the increased pressure such that most or all tissues of the tumor experience ischemia directly caused by compression caused by the tightened tension member.

In various embodiments, passing includes wrapping the tension member and/or a plurality of additional tension members along separate paths around the volumetric region. In various embodiments, each of the independent pathways completely circumscribe the tumor. In various embodiments, each independent path defines an independent plane extending through the tumor. In various embodiments, the independent planes intersect along a line through the tumor. In various embodiments, the independent planes intersect along a line outside the tumor. In various embodiments, the independent paths intersect at one or more points. In various embodiments, the one or more intersection points are external to the tumor. In various embodiments, tightening comprises tightening the tension member and/or at least one of the plurality of additional tension members to cause volumetric compression of the volumetric region. In various embodiments, an additional predetermined volumetric region surrounds at least another portion of the tumor, and wherein traversing further comprises deploying a plurality of windings around the additional volumetric region. In some embodiments, tightening comprises tightening the tension member and/or the plurality of additional tension members to collectively apply a compressive force toward the interior of the tumor. In some embodiments, the compression force is a radial compression force applied toward the center of the tumor.

In various embodiments, the volumetric region encompasses a majority of the volume of the tumor.

In various embodiments, the volumetric region encompasses the entire volume of the tumor.

In various embodiments, the tightening is performed using a tightening device, and the method further comprises: the tightening device is removed from the body before and/or during the maintenance of the increased pressure.

In various embodiments, the compression is continuously maintained at least until necrosis is achieved in at least a majority of all tissue of the tumor. In various embodiments, the compression is continuously maintained at least until necrosis is achieved in substantially all tissue of the tumor.

In various embodiments, compression is continuously maintained for a period of no less than 1 hour or no less than four hours. In some embodiments, compression is maintained continuously for a period of not less than eight hours. In some embodiments, compression is maintained continuously for a period of not less than 24 hours. In some embodiments, compression is maintained continuously for a period of no less than three days.

In various embodiments, tightening causes an increase in capillary blood pressure in a downstream region relative to the vessels supplying the tumor, thereby reducing or preventing oxygenated blood from migrating from the vessels to the tissue of the tumor and causing ischemia.

In various embodiments, tightening causes an increase in interstitial fluid pressure in the tumor and/or in the tissue of the organ surrounding the tissue, thereby reducing or preventing the migration of cellular nutrients and small molecules into the tumor.

In various embodiments, tightening the tension member increases the pressure within the tumor to a first level and damages tissue within the volumetric region, and the method further comprises: maintaining the tension members in a tightened state while tissue within the volumetric region that has been damaged swells in response to the injury, wherein the swelling of the tissue within the volumetric region increases the pressure within the tumor to a second level that exceeds the first level. In various embodiments, swelling of tissue within the volumetric region occurs through natural bodily processes in response to the injury, such that increasing the pressure within the tumor to a second level is an indirect result of tightening the tension members.

In various embodiments, the method further comprises: the tension member is threaded along a predetermined path line between the inlet opening and the outlet opening. In some embodiments, the access line protrudes across one or more blood vessels feeding the tumor such that tightening of the tensioning member directly causes occlusion of the one or more blood vessels.

In various embodiments, the tumor is mural, submucosal, or submucosal relative to the organ.

In various embodiments, at least a portion of the tumor is located between walls within the organ, and wherein passing the tension member within the organ comprises passing the tension member through the inter-wall portion of the organ. In some embodiments, passing the tensioning member through the interwall portion of the organ comprises passing the tensioning member around at least a portion of an interwall tumor located within the organ. In some embodiments, passing the tension member within the organ includes passing the tension member only through an intermural portion of the organ and/or tumor between the entrance opening and the exit opening. In some embodiments, passing the tension member within the organ includes passing the tension member only through an intermural portion of the organ and/or tumor between the entrance opening and the exit opening.

In various embodiments, the tumor is uterine fibroids.

In various embodiments, the method further comprises forming a surgical pathway from outside the body to the organ, wherein at least one of traversing, tightening, and maintaining is performed via the surgical pathway.

In various embodiments, the method further comprises performing an open procedure to provide access to the organ.

In various embodiments, tightening comprises or may be followed by the steps of: securing a first portion of the tension member protruding from the inlet opening to a second portion of the tension member protruding from the outlet opening, wherein the securing facilitates the maintaining. In some embodiments, the fixation is performed outside the boundaries of the organ. In some embodiments, tightening and securing is performed using a tightening device.

In some embodiments, the tightening device is removed from the body before or during maintenance. In some embodiments, securing includes attaching a fastener to the tension member. In some embodiments, securing includes crimping the fastener to securely grip the tension member. In some embodiments, the method further comprises: forming a surgical pathway from outside the body to the organ, wherein at least one of traversing, tightening, and maintaining is performed via the surgical pathway; and closing the surgical pathway while the tension member and fastener remain within the subject's body. In some embodiments, the tension member comprises a bioresorbable material and the fastener comprises a non-bioresorbable material, and the method further comprises: leaving the tension member within the subject's body for a time sufficient to allow the body to resorb the tension member; and leaving the fastener in the subject's body beyond a time sufficient to allow the body to resorb the tension member.

In various embodiments, passing the tension member includes advancing an end of the tension member through the exit opening, around the tumor, and through the entrance opening such that a first portion of the tension member protrudes from the organ through the exit opening and a second portion of the tension member protrudes from the organ through the entrance opening. In some embodiments, the method further comprises securing the first portion of the tension member to the second portion of the tension member. In some embodiments, the method further comprises: advancing an elongate member through the entrance opening, around the tumor, and through the exit opening; and coupling the elongate member to the tension member prior to passing the tension member therethrough, wherein passing the tension member comprises: while the elongate member is coupled to the tension member, the elongate member is withdrawn through the exit opening, around the tumor, and through the entrance opening.

In various embodiments, the method further comprises: a channel is formed around the volume area between the inlet opening and the outlet opening, wherein the passing is performed after the forming and mainly or completely within the channel. In some embodiments, passing includes pulling the tension member toward the inlet opening. In some embodiments, forming includes advancing a curved needle around the volumetric region. In some embodiments, forming further comprises: positioning an outer tube into the organ through the access opening to access the tumor, wherein advancing the curved needle comprises advancing the needle through a lumen of the outer tube. In some embodiments, positioning includes forming the inlet opening with a distal end of the outer tube. In some embodiments, positioning comprises placing the distal end of the outer tube adjacent a lateral limb of the tumor.

In various embodiments, the inlet opening is located at a first location on or adjacent the tumor and the outlet opening is located at a second location on or adjacent the tumor that is spaced apart from the first location such that the tumor is located between the inlet opening and the outlet opening.

In various embodiments, the tension member comprises a wire. In some embodiments, the wire comprises a suture-use wire.

In various embodiments, the tension member comprises a flexible strap.

In various embodiments, the tension member comprises at least one of an implant grade metal alloy, an implant grade polymer, an implant grade textile, and a biodegradable material.

In various embodiments, the tension member is configured with a yield strength or maximum tension of at least 25 newtons.

In various embodiments, passing includes wrapping more than half of the circumferential portion of the tumor with the tensioning member.

In various embodiments, tightening includes tightening the tension member to achieve the selected tension. In some embodiments, the selected tension is predetermined.

In various embodiments, the method further comprises measuring a tension force applied to the tension member during tightening.

In some embodiments, the method further comprises measuring pressure within the tumor during tightening.

In various embodiments, the volumetric region includes a portion of the surface of the organ. In some embodiments, the method further comprises extending a tensioning member over the portion of the organ surface between the entrance opening and the exit opening, wherein tightening the tensioning member comprises tightening the tensioning member around the portion of the organ surface. In some embodiments, the volumetric region includes the entire tumor.

In some embodiments, passing the tension member through and tightening the tension member is performed via a robotic system.

Example 2

A method for treating a tumor in a subject's body can comprise: deploying a plurality of windings of at least one tension member around a tumor, at least a portion of each of the windings being spaced apart from a portion of each adjacent winding; tightening the at least one tension member such that the plurality of windings collectively cause a volumetric compression on the tumor; and continuously maintaining volumetric compression to achieve ischemia in most or all tissues of the tumor.

In various embodiments, tightening comprises tightening the at least one tensioning member to achieve the selected tension within the tumor. In some embodiments, tightening further comprises tightening the at least one tensioning member to achieve the selected pressure within the tumor.

In various embodiments, tightening comprises tightening the at least one tensioning member to achieve a selected pressure within the tumor.

In various embodiments, tightening comprises tightening the at least one tension member such that each of the plurality of windings applies a compressive force toward the interior of the tumor. In some embodiments, the compression force is applied radially toward the center of the tumor.

Example 3

A method for treating a tumor in a subject's body can comprise: creating a surgical pathway into the body to access an organ surrounding the tumor; advancing, via the surgical pathway, the outer tube into the organ via an entrance opening at a surface of the organ, thereby forming a passage from the entrance opening to a first point adjacent a lateral limb of the tumor with a distal end of the outer tube; pushing the pre-curved needle through the lumen of the outer tube while the needle is in the straightened state until a distal portion of the pre-curved needle protrudes from the outer tube; pushing the pre-curved needle further beyond the distal end of the outer tube to allow the needle to resiliently regain a curved shape and extend the channel along a curved path from a first point to a second point surrounding a volumetric region relative to the first point, the volumetric region surrounding at least a portion of the tumour; forming an exit point proximate to the second point at the surface of the organ; passing the tension member primarily or entirely within the channel, resulting in a first portion of the tension member protruding from the organ via the inlet opening and a second portion of the tension member protruding from the organ via the outlet opening; tightening the tension member so as to achieve a volumetric compression of the volumetric region for increasing pressure within the tumor; and securing the first portion of the tension member to the second portion; wherein tightening is maintained after fixation to achieve ischemia in most or all tissues of the tumor.

In various embodiments, securing includes coupling a fastener to the first and second portions of the tension member to maintain the tension member in a tightened state. In some embodiments, the fastener comprises a ductile material, and wherein securing comprises crimping the fastener around the first and second portions of the tension member.

In various embodiments, forming includes advancing the stylet through the lumen of the pre-bent needle until the distal end of the stylet penetrates the surface of the organ, thereby forming the exit opening and extending the channel from the second point to the exit opening. In some embodiments, passing includes pulling the tension member through a passage from the exit opening to the entrance opening using a stylet, wherein the stylet has an anchoring member at its distal end configured for facilitating selective anchoring to the tension member.

Example 4

A method may include: circumscribing the tumor with at least one tensile member along a first path; circumscribing the tumor with the at least one tensioning member along a second path different from the first path; tightening the at least one tensioning member to compress the tumour along the first and second pathways to increase capillary and/or interstitial fluid pressure within the tumour above a threshold level sufficient to cause ischaemia of the tumour; and maintaining, via the at least one tension member, capillary blood pressure and/or interstitial pressure above a threshold level for a period of time sufficient to allow at least a portion of the tumor to necrose due to ischemia.

In various embodiments, the at least one tensioning member comprises a single tensioning member looped around the tumor along the first path and the second path.

In various embodiments, the at least one tensioning member comprises a first tensioning member and a second tensioning member, wherein circumscribing along the first path comprises circumscribing the tumor with the first tensioning member along the first path, and wherein circumscribing along the second path comprises circumscribing the tumor with the second tensioning member along the second path.

In various embodiments, the first path defines a first plane extending through the tumor and the second path defines a second plane extending through the tumor, the second plane being at an angle relative to the first plane. In some embodiments, the angle is not less than 30 degrees. In some embodiments, the first plane and the second plane intersect along a line extending through the tumor. In some embodiments, the line extends through the center of the tumor.

In various embodiments, tightening comprises tightening the at least one tensioning member to collectively apply a compressive force along the first and second paths toward the interior of the tumor. In some embodiments, the compression force is a radial compression force applied toward the center of the tumor.

In various embodiments, the threshold level of interstitial fluid pressure is not less than 1 mmHg, or not less than 2 mmHg, or not less than 4 mmHg.

In various embodiments, the threshold level of capillary blood pressure is not less than 10 mmHg, or not less than 20 mmHg, or not less than 25 mmHg.

In various embodiments, the period of time sufficient to allow at least a portion of the tumor to necrose due to ischemia is not less than four hours.

In various embodiments, each circumscribing step comprises advancing the at least one tensioning member around the tumor at an exterior of a prosthetic capsule surrounding the tumor.

In various embodiments, the method further comprises: forming a first pathway by inserting a tubular member into a patient until a distal end of the tubular member is proximate to a tumor; and advancing the needle beyond the distal end of the tubular member along a curved path extending around at least a portion of the tumor. In some embodiments, the needle is pre-curved, and the method further comprises: maintaining the needle in a straightened configuration when the needle is located within the tubular member; and advancing the needle beyond the distal end of the tubular member to allow the needle to resiliently return to the curved configuration and form a curved path around at least a portion of the tumor. In some embodiments, circumscribing the tumor with the at least one tensioning member along the first path comprises: coupling a stylet to the at least one tension member; and passing a stylet along a first path while coupled to the at least one tension member.

Example 5

A method may include: volumetrically compressing a tumor in a patient to increase pressure within the tumor above a threshold level sufficient to cause ischemia of the tumor; and maintaining the pressure above the threshold level for a period of time sufficient to allow at least a portion of the tumor to necrose due to ischemia.

In various embodiments, volumetrically compressing the tumor includes volumetrically compressing only a portion of the tumor.

In various embodiments, the method further comprises circumscribing the tumor with at least one exogenous device relative to the patient, wherein volumetrically compressing the tumor and maintaining the pressure above the threshold level are achieved via the at least one device. In some embodiments, the volumetric compression of the tumor is achieved solely by the contour around the tumor reduction device. In some embodiments, maintaining the pressure above the threshold level is achieved only by a reduced contour around the tumor maintenance device. In some embodiments, volumetrically compressing the tumor includes contouring around the tumor reduction device, and maintaining the pressure above the threshold level is achieved only by contouring around the tumor reduction device. In some embodiments, the device comprises at least one tensioning wire. In some embodiments, the device comprises a mesh comprising the at least one tensioning wire.

In various embodiments, volumetrically compressing includes compressing the tumor along at least a first compression line and a second compression line that extend along different paths around an outer surface of the tumor. In some embodiments, the first compression line and the second compression line are non-intersecting. In some embodiments, the first compression line and the second compression line intersect at an intersection point. In some embodiments, the first compression line and the second compression line intersect at no less than two spaced apart intersection points. In some embodiments, the method further comprises wrapping the tumor with at least one tensioning member to define a three-dimensional shape around the tumor, wherein volumetrically compressing the tumor comprises reducing a size of the three-dimensional shape. In some embodiments, reducing the size of the three-dimensional shape is achieved by tightening the at least one tension member. In some embodiments, the three-dimensional shape comprises a plurality of loops. In some embodiments, at least one of the loops overlaps another of the loops. In some embodiments, the loops intersect at one or more intersection points. In some embodiments, the loops define planes that are angularly offset from one another. In some embodiments, the planes intersect along a line through the tumor. In some embodiments, each of the loops is substantially circular. In some embodiments, the three-dimensional shape comprises a helix that extends along the length of the tumor and extends through an angular rotation of no less than 360 degrees.

In various embodiments, the method further comprises passing a tensioning member through the tumor, wherein volumetrically compressing the tumor is achieved via the tensioning member.

In various embodiments, volumetrically compressing the tumor includes continuously applying a compression force toward an interior of the tumor. In some embodiments, the compression force comprises a radial compression force applied toward the center of the tumor.

In various embodiments, the threshold level of pressure is not less than 10 mmHG, or not less than 20 mmHG, or not less than 50 mmHG, or not less than 75 mmHG, or not less than 100 mmHG.

Example 6

A method may include: passing a tensioning member through an interwall portion of an organ and around a tumor positioned at least partially in the interwall portion of the organ; tightening the tensioning member at a selected tightening force to cause compression of the tumor, thereby directly increasing pressure within the tumor sufficient to effect ischemia of the tumor; and continuously maintaining the increased pressure until most or all tissues of the tumor undergo necrosis caused by ischemia.

Example 7

A method may include: placing a medical device around the tumor such that the medical device defines a three-dimensional shape surrounding the tumor; transitioning the medical device to a reduced profile to reduce the size of the three-dimensional shape and thereby achieve volumetric compression of the tumor in an amount sufficient to achieve ischemia of the tumor; and maintaining the medical device in the reduced profile until the ischemia causes necrosis of at least a portion of the tumor.

In various embodiments, transitioning the medical device to a reduced profile increases pressure within the tumor to achieve ischemia of the tumor.

In various embodiments, the medical device includes one or more tension members. In some embodiments, the device comprises a plurality of tension members, wherein placing the medical device around the tumor comprises sequentially advancing each tension member around the tumor, and wherein transitioning the medical device to the reduced profile comprises tensioning each tension member. In some embodiments, each tension member is placed around the tumor and tightened before the subsequent tension members are placed and tightened. In some embodiments, the medical device further comprises one or more anchors coupled to the one or more tension members.

In various embodiments, the increased pressure is continuously maintained until ischemia causes necrosis of at least a majority of the tumor.

Example 8

An apparatus for compressing a tumor in an organ of a body of a subject may comprise: an elongate body configured for accessing a surface of an organ proximate a tumor via a surgical pathway formed in a body of a subject; a tightening mechanism for tightening a tension member extending around a volumetric portion of a tumor, wherein a first portion of the tension member protrudes from an inlet opening at a surface of an organ and a second portion of the tension member protrudes from an outlet opening at the surface of the organ, the tightening mechanism comprising: a first puller member configured for anchoring to a first portion of the tension member; and a force manipulator unit configured for applying a tensioning force via the first puller member to force the tensioning member into a tightened state sufficient to compress the volume portion and/or increase pressure within the tumor; and a securing mechanism configured for securing the first portion of the tension member to the second portion via the elongated body proximate a surface of the organ for maintaining the tension member in a tightened state, including after the tightening mechanism has been disengaged from the tension member.

The apparatus may further comprise a measurement unit configured for indicating a magnitude related to the tension force, a change in compression of the volume portion and/or a change in pressure within the tumor when the tension member is tightened by the tightening mechanism. In various embodiments, the first pulling member is configured to anchor and pull a tension member configured as a flexible wire or strip. In various embodiments, the tension member comprises at least one of an implant grade metal alloy, an implant grade polymer, an implant grade textile, and a biodegradable material.

In various embodiments, the tightening mechanism is configured to limit the force manipulator unit to apply a tension force from the range of 25N to 100N. In various embodiments, the tightening mechanism is configured to facilitate presetting the selected tightening force and automatically cause the force manipulator unit to apply the selected tightening force. In various embodiments, the tightening mechanism is configured to prevent tensioning the tension member beyond a selected tension force.

In various embodiments, the tightening mechanism is configured to apply the force manipulator unit to automatically increase the tension force to the tension member gradually, continuously, or discretely until a selected tension force is reached. In various embodiments, the tightening mechanism is configured to limit manual use to a gradual, continuous, or discrete increase in the tightening force until a selected tightening force is reached.

In various embodiments, the measurement unit comprises a scale having a set of values within an acceptable range of magnitudes.

In various embodiments, the securing mechanism is configured for applying the fastener to secure the first portion of the tension member to the second portion for an extended period of time sufficient to cause ischemia and/or necrosis in most or all tissue of the tumor when the volume portion is continuously compressed and/or the tumor is forced to increase pressure therein by the tension member during the period of time.

In various embodiments, the securing mechanism is configured to couple the fastener to the first and second portions of the tension member to maintain the tension member in a tightened state. In various embodiments, the fastener comprises a ductile material, and wherein the securing mechanism is configured to crimp the fastener around the first and second portions of the tension member. In various embodiments, the fastener includes a tubular fastener body sized to allow the tension member to pass therethrough, wherein, when applied to crimp the fastener, the securing mechanism is configured to compress and/or bend a portion of the fastener body, thereby securing the first and second portions of the tension member to the portion of the fastener body.

In various embodiments, the elongate body comprises a barrel and an anvil disposed at a distal end of the barrel, and the securing mechanism comprises a hammer head slidable in the barrel along a longitudinal axis of the barrel, wherein the securing mechanism is configured to force the hammer head to press the portion of the fastener body against the anvil for compressing and/or bending the portion of the fastener body when crimping the fastener. In various embodiments, the anvil includes an anvil lumen sized to receive the fastener body therein. In various embodiments, the longitudinal axis of the anvil lumen is angled relative to the longitudinal axis of the barrel. In various embodiments, the securing mechanism includes a positioning spring configured to force the hammer head into a nominal position such that the hammer head protrudes into the anvil lumen in the absence of a fastener body in the anvil lumen, and is configured to retract when the fastener body is fully received in the anvil lumen. In various embodiments, when the fastener body is fully received in the anvil lumen, the positioning spring is forced to preload under a preload force sufficient to affect the anchoring of the fastener body to the anvil. In various embodiments, the securing mechanism includes a retraction spring configured to force the ram to retract and disengage from the compressed and/or curved portion of the fastener body at the end of or immediately after crimping the fastener.

In various embodiments, the securing mechanism is functionally independent of the tightening mechanism.

In various embodiments, when the force manipulator unit is continuously or repeatedly applied to tighten the tension member until the selected tension is reached, the tightening mechanism is configured to sequentially perform the following steps: pulling the first and second portions of the tension member reciprocally from a relaxed state until one of the first and second portions of the tension member reaches a taut state; pulling the other of the first and second portions of the tension member into a taut state; and reciprocally pulling the first and second portions of the tension member from a taut state until a selected tension is reached in the tension member.

In various embodiments, the second portion of the tension member is fixed relative to the first puller member.

In various embodiments, the tensioning mechanism includes a second puller member configured to be anchored to a second portion of the tension member, wherein the force manipulator unit is configured to apply tension via the second puller member to force the tension member into a tightened state between the first puller member and the second puller member. In various embodiments, the first puller member and the second puller member are functionally and/or structurally independent of each other in at least one of rotational speed and pulling force. In various embodiments, the tightening mechanism includes a tension force transmitting gear configured to reciprocally transmit force from the force manipulator unit to the first and second pull members. In various embodiments, a differential gear rotatable with the tension transfer gear reciprocally engages a first pull gear fixedly connected to a first pull member and a second pull gear fixedly connected to a second pull member, wherein rotation of the tension transfer gear transfers a transferred force to rotate the first and second pull gears and equally distribute therebetween through the differential gear while permitting differential relative rotation between the first and second pull gears.

In various embodiments, the force manipulator unit is selectively connectable to the power source via a computerized controller. In various embodiments, the force manipulator unit may be manually operated by pressing the trigger, wherein the tightening mechanism is configured for incrementally increasing the tightening force to the tension member during at least one cycle of the pressing motion of the trigger and for maintaining the tightening force when the trigger is withdrawn after each of said at least one cycle of the pressing motion. In various embodiments, the tightening mechanism includes a tension force transmitting gear configured to transmit force from the force manipulator unit to the first puller member.

In various embodiments, the force manipulator unit may be connected to the tension force transmitting gear by a clutch member that is selectively switchable between engagement and disengagement with the tension force transmitting gear. In various embodiments, the trigger has a first range of motion when the clutch member is engaged with the tension transfer gear and a second range of motion when the clutch member is disengaged from the tension transfer gear, the second range of motion being greater than the first range of motion, wherein the force manipulator unit is prevented from transmitting force to the securing mechanism when the trigger is depressed to an entire range of the first range of motion and the force manipulator unit is configured to transmit force to the securing mechanism when the trigger is depressed to an entire range of the second range of motion.

In various embodiments, the clutch member is configured for switching into engagement with the fixation force transmission gear when the clutch member is disengaged from the tension transmission gear, thereby facilitating force transmission from the force manipulator unit for operating the fixation mechanism.

In various embodiments, the clutch member is connected to a selector switch configured to facilitate selective manual shifting of the clutch member between: engaging the tightening-force transmitting gear after disengaging from the fixed-force transmitting gear; and engaging with the fixed force transmission gear after disengaging from the tightening force transmission gear. In various embodiments, the selector switch is further configured to control a range of motion of a trigger for manually operating the force manipulator, wherein a first range of motion limited by the selector switch when the clutch member is engaged with the stationary force transmitting gear is greater than a second range of motion limited by the selector switch when the clutch member is engaged with the tightening force transmitting gear.

Example 9

An apparatus for passing a tension member around a tumor in an organ of a subject's body may comprise: an elongate body configured for accessing a surface of an organ proximate a tumor via a surgical pathway formed in a body of a subject; and a tension member passing mechanism configured for affecting the organ from the proximal end of the elongate body via the distal end of the elongate body for forming an inlet opening and an outlet opening at a surface of the organ and for forming a surgical channel between the inlet opening and the outlet opening in a close-fitting manner around a predetermined volume portion of the organ surrounding at least a portion of the tumor; the tension member traversing mechanism is further configured for extending the tension member around a volumetric portion of the tumor resulting in wherein a first portion of the tension member protrudes from the organ via the inlet opening and a second portion of the tension member protrudes from the organ via the outlet opening.

In various embodiments, the tension member threading mechanism comprises: an outer tube configured for forming an inlet opening and for penetrating into an organ with a sharp distal end thereof to a selected depth and positioned relative to the volume portion; and a curved needle configured for advancement through the lumen of the outer tube while forcing the distal curved portion thereof to a straightened shape until the distal curved portion protrudes from the outer tube and is allowed to resiliently regain the curved shape; wherein the tension member traversing mechanism is configured to form a surgical channel in the organ from the access opening by advancing the distal end of the outer tube to a selected depth in the organ and positioning from the access opening, and further advancing the distal curved portion from the outer tube in the organ.

In various embodiments, the tension member passing mechanism further comprises a stylet configured for: travels within the lumen of the curved needle and projects from the distal curved portion of the curved needle. In various embodiments, by advancing the stylet in the organ from the distal portion of the curved needle, the tension member passing mechanism is configured to extend the surgical channel toward the surface of the organ and form an exit opening with the distal end of the stylet.

In various embodiments, the stylet includes an anchor member at its distal end configured for selective anchoring to a tension member for facilitating pulling of the tension member along the channel. In various embodiments, the anchoring member includes a loop sized to receive a length of the tension member therethrough.

In various embodiments, the tension member threading mechanism is configured to anchor the tension member and pull it into the exit opening and through the surgical channel after the surgical channel is formed.

In various embodiments, the apparatus further comprises a tightening mechanism and/or a securing mechanism configured for securing the first portion of the tension member to the second portion via the elongated body proximate to the surface of the organ for maintaining the tension member in a tightened state, including after the tightening mechanism has been disengaged from the tension member.

The device may be provided in a kit additionally comprising a further device comprising: an elongate body configured for accessing a surface of an organ proximate a tumor via a surgical pathway formed in a body of a subject; a tightening mechanism for tightening a tension member extending around a volumetric portion of a tumor, wherein a first portion of the tension member protrudes from an inlet opening at a surface of an organ and a second portion of the tension member protrudes from an outlet opening at the surface of the organ, the tightening mechanism comprising: a first puller member configured for anchoring to a first portion of the tension member; and a force manipulator unit configured for applying a tensioning force via the first puller member to force the tensioning member into a tightened state sufficient to compress the volume portion and/or increase pressure within the tumor; and a securing mechanism configured for securing the first portion of the tension member to the second portion via the elongated body proximate a surface of the organ for maintaining the tension member in a tightened state, including after the tightening mechanism has been disengaged from the tension member.

Example 10

A robotic system may include a tightening mechanism configured to tighten a tension member extending around a volumetric portion of a tumor, wherein a first portion of the tension member protrudes from an entrance opening at a surface of an organ and a second portion of the tension member protrudes from an exit opening at the surface of the organ, and/or a fixation mechanism, the tightening mechanism comprising: a first puller member configured for anchoring to a first portion of the tension member; and a force manipulator unit configured for applying a tensioning force via the first puller member to force the tensioning member into a tightened state sufficient to compress the volume portion and/or increase pressure within the tumor; the fixation mechanism is configured for securing the first portion of the tension member to the second portion via the elongated body proximate a surface of the organ for maintaining the tension member in a tightened state, including after the tightening mechanism has been disengaged from the tension member.

The robotic system may further include a tension member passing mechanism configured for affecting the organ from the proximal end of the elongated body via the distal end of the elongated body for forming an inlet opening and an outlet opening at a surface of the organ and for forming a surgical channel between the inlet opening and the outlet opening in a close-fitting manner around a predetermined volume portion of at least a portion of the organ surrounding the tumor; the tension member traversing mechanism is further configured for extending the tension member around a volumetric portion of the tumor resulting in wherein a first portion of the tension member protrudes from the organ via the inlet opening and a second portion of the tension member protrudes from the organ via the outlet opening.

Example 11

A method for compressing a tumor in an organ of a body of a subject may comprise: inserting the elongate body through a surgical pathway formed in the body of the subject until reaching a surface of an organ proximate the tumor; tightening a tension member extending around a volumetric portion of the tumor using a tightening mechanism, wherein a first portion of the tension member protrudes from an entrance opening at a surface of the organ and a second portion of the tension member protrudes from an exit opening at the surface of the organ, the tightening comprising: anchoring a first portion of the tension member to the first puller member; and applying tension via the first puller member by the force manipulator to force the tension member into a tightened state sufficient to compress the volume portion and/or increase pressure within the tumor; and securing the first portion of the tensioning member to the second portion via the elongate body using the securing mechanism proximate the surface of the organ for maintaining the tensioning member in a tightened state, including after the tightening mechanism has been disengaged from the tensioning member.

In various embodiments, applying the tensioning force is after securing the second portion of the tensioning member relative to the first puller member.

In various embodiments, the tensioning mechanism includes a second pulling member configured to be anchored to the second portion of the tension member, wherein applying the tensioning mechanism for tensioning the tension member further comprises: a first portion of the tension member is anchored to the first puller member and a tensioning force is applied to force the tension member into a tightened state between the first puller member and the second puller member.

The method may further comprise: when the tension member is tightened by the tightening mechanism, a magnitude related to the tension force, a compression change of the volume portion, and/or a pressure change within the tumor is measured.

The method may further comprise presetting the selected tensioning force into a tightening mechanism for automatically causing the force manipulator to apply the selected tensioning force.

The method may further include preventing tensioning of the tension member beyond the selected tensioning force.

In various embodiments, securing comprises applying a fastener to secure the first portion to the second portion of the tensioning member for an extended period of time sufficient to cause ischemia and/or necrosis in most or all tissue of the tumor when the volume portion is continuously compressed and/or the tumor is forced to increase pressure therein by the tensioning member during the period of time. In various embodiments, the fastener comprises a ductile material, and wherein securing comprises crimping the fastener around the first and second portions of the tension member. In various embodiments, securing comprises: the method includes the steps of passing a tension member through a tubular fastener body of the fastener, and compressing and/or bending a portion of the fastener body for securing a first portion and a second portion of the tension member to the portion of the fastener body. In various embodiments, the elongate body comprises a barrel and an anvil disposed at a distal end of the barrel, wherein the pressing and/or bending comprises forcing the hammer head to slide in the barrel along its longitudinal axis and press the portion of the fastener body against the anvil.

In various embodiments, the securing is functionally independent of tightening, such that the securing can be performed before, after, or during tightening.

The method may further include continuously or repeatedly applying the force manipulator to tighten the tension member until the selected tension is reached. In various embodiments, continuously or repeatedly applying force to the manipulator sequentially causes the following steps: pulling the first and second portions of the tension member reciprocally from a relaxed state until one of the first and second portions of the tension member reaches a taut state; pulling the other of the first and second portions of the tension member into a taut state; and reciprocally pulling the first and second portions of the tension member from a taut state until a selected tension is reached in the tension member.

As used herein, each of the following terms, written in the singular form: 'a', 'an' and 'the' mean 'at least one' or 'one or more'. The phrase 'one or more' is used herein without altering the intended meaning of 'a', 'an', and 'the'. Thus, the terms 'a', 'an' and 'the' as used herein are intended to refer to and encompass a plurality of the recited entities or objects as well, unless the context clearly indicates otherwise, unless otherwise explicitly defined or stated herein, or unless the context clearly indicates the contrary. For example, as used herein, the phrase: the 'unit', 'device', 'component', 'mechanism', 'component', 'element' and 'step or procedure' can also refer to and encompass a plurality of units, a plurality of devices, a plurality of components, a plurality of mechanisms, a plurality of components, a plurality of elements, and a plurality of steps or procedures, respectively.

As used herein, each of the following terms: "comprising," "including," "having," "containing," "including," and "containing" and grammatical variations, derivatives, and/or variations thereof mean "including, but not limited to," and are to be taken as specifying the stated component(s), feature(s), characteristic(s), parameter(s), integer(s) or step(s), and not excluding the addition of one or more additional components, feature(s), characteristic(s), parameter(s), integer(s), step(s), or group thereof. Each of these terms is considered to be equivalent in meaning to the phrase "consisting essentially of.

The term "method" as used herein refers to steps, procedures, means, or/and techniques for accomplishing a given task, including but not limited to those steps, procedures, means, or/and techniques known to, or readily developed from known steps, procedures, means, or/and techniques by practitioners of the relevant art(s) of the disclosed invention.

Throughout this disclosure, numerical values for parameters, features, characteristics, objects, or dimensions may be stated or described in terms of a numerical range format. As used herein, such numerical range format illustrates implementation of some exemplary embodiments of the present invention, and does not rigidly limit the scope of exemplary embodiments of the present invention. Thus, a stated or described numerical range also refers to and encompasses all possible subranges and individual numerical values within the stated or described numerical range (where numerical values may be expressed as integers or fractions as a whole). For example, a stated or described numerical range of 'from 1 to 6' also refers to and encompasses all possible subranges (such as 'from 1 to 3', 'from 1 to 4', 'from 1 to 5', 'from 2 to 4', 'from 2 to 6', 'from 3 to 6', etc.) and individual numerical values (such as '1', '1.3', '2', '2.8', '3', '3.5', '4', '4.6', '5', '5.2', and '6' within the stated or described numerical range of 'from 1 to 6'). This applies regardless of the numerical width, extent, or size of the numerical ranges set forth or described.

Further, for the purpose of stating or describing a numerical range, the phrase 'in a range between about a first numerical value and about a second numerical value' is considered equivalent to and synonymous with the phrase 'in a range from about the first numerical value to about the second numerical value', and thus, the two equivalent meaning phrases are used interchangeably. For example, to state or describe a numerical range for room temperature, the phrase 'room temperature refers to a temperature in the range between about 20 ℃ and about 25 ℃ is considered equivalent to and synonymous with the phrase' room temperature refers to a temperature in the range from about 20 ℃ to about 25 ℃.

The term "about" as used herein refers to ± 10% of the stated value.

It will be appreciated that certain aspects, features and characteristics of the present invention, which are, for clarity, described and illustrated in the context or format of separate embodiments, may also be described and illustrated in any suitable combination or sub-combination in the context or format of a single embodiment. Conversely, various aspects, features, and characteristics of the present invention, which are illustratively described and presented in combination or sub-combination in the context or format of a single embodiment, may also be illustratively described and presented in the context or format of a plurality of separate embodiments.

While the present invention has been illustratively described and presented by way of specific exemplary embodiments and examples thereof, it is evident that many alternatives, modifications and/or variations thereof will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications, and/or variations that fall within the spirit and broad scope of the appended claims.

All documents, patents, and/or patent applications cited or referred to in this disclosure are incorporated by reference in their entirety into the specification to the same extent as if each individual document, patent, or/and patent application was specifically and individually indicated to be incorporated by reference herein. In addition, citation or identification of any reference in this specification shall not be construed or construed as an admission that such reference is available as indicating or corresponding to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting.