WO2024072287A1

WO2024072287A1 - In-situ cryoablation device and method of producing the device

Info

Publication number: WO2024072287A1
Application number: PCT/SE2023/050933
Authority: WO
Inventors: Mehdy FARHANG
Original assignee: Farhang Mehdy
Priority date: 2022-09-26
Filing date: 2023-09-25
Publication date: 2024-04-04
Also published as: SE2251106A1

Abstract

A device (101) for in-situ cryoablation therapy of a tumor in a tissue comprises a container (102) for a coolant. The container comprises a coolant inlet (103) for receiving the coolant and at least one opening (104) in the container wall. The opening (104) is configured to allow a coolant within said container (102) to come in direct contact with the tumor-containing section of the tissue. At least one edge of the at least one opening is provided with a flange (105) protruding from the container wall. A tissue-facing surface of the flange (105) is provided with a bonding member (106) for fixing the tissue-facing surface of the flange to the tumor-contain- ing section of the tissue such that leakage of any coolant though said at least one openings (104) is essentially prevented when the device (101) is applied to the tumor-containing section of the tissue.

Description

IN-SITU CRYOABLATION DEVICE AND METHOD OF PRODUCING THE DEVICE

TECH N ICAL FI ELD

The present invention relates to device for cryoablation therapy, and in particular to a device

5 for in-situ cryoablation therapy of tumors.

BACKGROU N D

The treatment of bone tumors (musculoskeletal tumors) has historically involved extensive surgeries with major resection, and possibly even amputation of a limb, joint, or the like. Even when the bone tumors are treated by chemo or radiation therapy, it is often necessary to perform surgery to remove the tumorous bone.

Thus, some form of reconstruction has been necessary to fill the remaining defect, for example by endoprostheses, allograft bone (bone from others), autograft (bone form other parts of the same patient) or artificial bone substitutes. However, these reconstructions can be

15 clunky, awkward, and in particular prone to infections which can be especially threatening for cancer patients with, generally, poor health and a weak immune system. The reconstructions can furthermore cause metal ions to form in the blood which can lead to an array of dangerous conditions including aseptic lymphocyte-dominant vasculitis-associated lesion (ALVAL). Moreover, reconstructions have a limited life span after which they will need to be replaced.

20 As an alternative method of treatment, cryoablation has therefore been used. Cryoablation is a method of, for therapeutic purposes, destroying malicious or otherwise unwanted tissue by freezing of said tissue. Cryoablation can thus be used for treatment of tumors when other surgical techniques are inappropriate, suboptimal, unavailable, or impossible to perform. However, it is important that the cryoablation therapy does not freeze and destroy healthy tissue

25 surrounding the tumor.

A common method of performing cryoablation therapy is by penetration of the tumor by a cooled needle so as to freeze the tumor by said needle. However, although this method provides local freezing, it may be difficult to ensure that the entire tumor is destroyed. Furthermore, depending on where the tumor is located it may not be possible to access the tumor by a

30 needle, in particular if the tumor is located inside a bone (e.g. a musculoskeletal tumor), which may require removal of a section of the bone for allowing access for the needle.

A technique was therefore developed later in which penetration of the tumor was not needed. In this technique, the tumorous bone is cut off at both ends and removed from the body. The tumorous bone section is then frozen by submerging it in a very cold liquid. The bone section may then be put back into the body using screws, plates and the like. Such a procedure inevitably leads to very long healing times involving significant rehabilitation (since the bone is cut off at both ends) and is very uncomforting and painful for the patient.

An improved method was thus proposed in which the bone is only cut off in one end. The bone, still attached in one end (e.g. in an end leading to a joint), is freed from surrounding soft tissue (muscles, nerves, sinews and the like) and turned (rotated) outwards, such that the tumorous bone section points away from the limb or body. The freed tumorous bone section may then be submerged in a very cold liquid which freezes and destroys the tumor cells. After the tumor cells are destroyed, the bone can be reattached at the cut-off end using screws, plates and the like. However, it is often difficult, and sometimes impossible, to free the bone section from surrounding tissue in a way that allows the bone to be rotated out so as to be frozen.

From the above, it is understood that there is room for improvements and the invention aims to solve or at least mitigate the above and other problems.

SUMMARY

The invention is defined by the appended independent claims. Additional features and advantages of the concepts disclosed herein are set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the described technologies. The features and advantages of the concepts may be realized and obtained by means of the instruments and combinations particularly pointed out in the appended claims. These and other features of the described technologies will become more fully apparent from the following description and appended claims, or may be learned by the practice of the disclosed concepts as set forth herein.

In a first aspect there is provided a device for in-situ cryoablation therapy of a tumor in a tissue, the device comprising: a container for a coolant at a temperature of below negative 60 degrees Celsius, wherein: the container is formed of a container wall; and the container comprises a coolant inlet for receiving the coolant; wherein the container wall comprises an edge that defines an opening in the container wall for allowing direct contact between the coolant and a section of the tissue containing the tumor, when the coolant is in the container; wherein the edge is provided with a flange protruding from the container wall, wherein the flange has a pre-determined shape that conforms to the tumor-containing section of the tissue; wherein a tissue-facing surface of the flange is provided with a bonding member for fixing the tissuefacing surface of the flange to the tumor-containing section of the tissue. Preferably, the bonding member is further configured to seal a contact surface between the tissue-facing surface of the flange and the tumor-containing section of the tissue when the flange is placed against the tumor-containing section of the tissue.

Preferably, the bonding member comprises a water absorbent foam.

Preferably, the water-absorbent foam is a polyurethane foam.

Preferably, the container is configured to enclose the tumor-containing section of the tissue; and the edge of the container wall is configured to surround an end portion of the tumor-containing section of the tissue.

Preferably, the edge is a first edge defining a first opening, and wherein the container wall further comprises a second edge defining a second opening; wherein the first edge is configured to surround a first end portion of the tumor-containing section of the tissue and the second edge is configured to surround a second end portion of the tumor-containing section of the tissue, such that a portion of the tumor-containing section of the tissue between the first and second end portions is enclosed by the container and extends between the first and second openings.

Preferably, the container wall is formed of two separate parts that are configured to be joined together.

Preferably, the device further comprises fastening means for joining the two parts together.

Preferably, the flange is configured to be placed against the tumor-containing section of the tissue such that the tumor-containing section of the tissue remains substantially outside of the container, and wherein the opening defined by the edge of the container wall is configured to, at least partially, cover the tumor-containing section of the tissue.

Preferably, the surface of the flange comprises at least one extension configured to receive one or more of: an attachment means for attaching the device to the tissue, and a probe for measuring the temperature of the tissue.

Preferably, in use, the opening is sealed by the tumor-containing section of the tissue together with the bonding member.

Preferably, the device further comprises: at least one probe comprising: a temperature sensor for measuring a temperature of the tissue; and a heating means for heating the tissue; and a processor configured to initiate the heating means in dependence on a temperature measured by the temperature sensor being below a threshold temperature.

In a second aspect there is provided a method of producing an in-situ cryoablation device as disclosed herein, the method comprising: performing a 3D scan of a tissue comprising one or more tumors in order to obtain a 3D model of the tissue; manufacturing, in dependence on the 3D model, a device with a container formed of a container wall comprising an edge that defines an opening in the container wall, wherein the edge is provided with a tissue-conforming flange; and attaching a water absorbent foam to a tissue-facing surface of the tis-sue-conform- ing flange.

Preferably, the 3D scan is performed by a non-invasive method.

Preferably, the 3D scan is one or more of: an X-ray scan, a magnetic resonance imaging scan and an ultrasound scan.

Preferably, the method further comprises one or more of the steps of: wetting the water absorbent foam with sterile water; and sterilizing the container.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to best describe the manner in which the above-described aspects are implemented, as well as define other advantages and features of the disclosure, a more particular description is provided below and is illustrated in the appended drawings. Understanding that these drawings depict only exemplary aspects of the invention and are not therefore to be considered to be limiting in scope, the exampleswill be described and explained with additional specificity and detail through the use of the accompanying drawings in which:

Fig. 1 shows a block diagram of a cryoablation device according to disclosed aspects;

Fig. 2 shows a method of producing a cryoablation device;

Fig. 3 shows an exploded view of a simplified cryoablation device according to a first aspect;

Fig. 4a shows a side view of a cryoablation device according to the first aspect;

Fig. 4b shows a top view of a cryoablation device according to the first aspect;

Fig. 5a shows a cryoablation device according to the first aspect during use;

Fig. 5b shows a cross-section of a cryoablation device according to the first aspect during use;

Fig. 5c shows a cross-section of a tissue-conforming rim of the first aspect during use;

Fig. 6 shows a cryoablation device according to the first aspect during use;

Fig. 7 shows a cryoablation device according to the second aspect;

Fig. 8 shows a cryoablation device according to the second aspect during use; and Fig. 9 shows a cryoablation device according to the second aspect during use.

Further, in the figures like reference characters designate like or corresponding elements or parts throughout the several figures. The first digit in the reference character denotes the first figure in which the corresponding element or part appears.

DETAILED DESCRIPTION

Various embodiments of the disclosed methods and arrangements are discussed in detail below. While specific implementations are discussed, it should be understood that this is done for illustration purposes only. A person skilled in the relevant art will recognize that other components, configurations, and steps may be used without parting from the spirit and scope of the disclosure.

In the description and claims the words “comprise”, “include”, and variations of the words, such as “comprising” and “comprises”, “including”, “includes”, do not exclude other elements or steps.

Hereinafter, certain aspects will be described more fully with reference to the accompanying drawings. It will be apparent to those skilled in the art that various modifications and variations can be made without departing from the inventive concept. Other aspects will be apparent to those skilled in the art from consideration of the specification and practice disclosed herein.

The aspects herein are provided by way of example so that this disclosure will be thorough and complete, and will fully convey the scope of the inventive concept, and that the claims be construed as encompassing all modifications, equivalents and alternatives of the present inventive concept which are apparent to those skilled in the art to which the inventive concept pertains. If nothing else is stated, different aspects may be combined with each other.

Tumors, such as cancerous tumors, may be present in different tissues in the body. For example, tumors may be present in hard tissue, such as bone tissue (osseus tissue), and/or soft tissue. Examples of bone tissue include cortical (compact) bone and cancellous (spongy) bone. Other types of tissue found in bones include bone marrow, endosteum, periosteum, nerves, blood vessels and cartilage. Examples of soft tissue include muscle, tendons, ligaments, fat, fibrous tissue, lymph and blood vessels, fasciae, and synovial membranes.

The inventor has realized that it is possible to treat tumors in tissue by in-situ cryoablation of said tumors.

Throughout this disclosure, the term “cryoablation” will be used to describe the destruction of cells through freezing. Throughout this disclosure, the term “in-situ” will be used to describe something in its natural or original position or place, e.g. as it appears in a normal and healthy body. For example, an in-situ treatment of tissue describes an intra-corporal treatment of tissue that is performed while said tissue remains in its usual place in the body.

To achieve in-situ cryoablation, the inventor has developed a novel cryoablation device. The cryoablation device can be used to successfully freeze a tumor in tissue while the tissue remains in its usual place in the body. In other words, the cryoablation device can be used for intra-corporal freezing of a tumor. Furthermore, the cryoablation device allows controlled cryoablation of the tumor(s) without penetrating or entering the tumor.

Thus, the cryoablation device according to aspects is particularly useful for treatment of bone tumors. The proposed cryoablation device also reduces the risk of freezing surrounding healthy tissue while performing the cryoablation therapy. The cryoablation device makes it possible to insert probes in predetermined locations, at predetermined depths, and in predetermined directions, so as to measure temperature in surrounding tissue, and if needed, to heat up surrounding healthy tissue. The heating may be performed (by the probes) by radiofrequency and/or microwaves or the like to prevent cold damage to the surrounding healthy tissue.

The proposed cryoablation device, and its associated method of treatment, thus significantly reduces the healing time, and risk for infections, compared to previously known methods of treatment. Furthermore, there is no need for any reconstruction or prosthesis.

Fig. 1 shows a block diagram of a cryoablation device 101 according to aspects. The cryoablation device 101 comprises a coolant inlet 103, a container 102, an opening 104 with a tissue-conforming flange 105, and a bonding member 106.

The container 102 is an at least partially closed volume configured to store or hold a coolant. The container is formed of a container wall. In other words, the container wall defines the container. The container wall 102 is made from a biocompatible material that can withstand the cold temperatures of the coolant.

Biocompatibility may include meeting the requirements for one or more of the following certifications: “USP Class l-Vr, “US FDA’s Guidance for Intact Skin Surface Devices”, “ISO 10993-5”, “ISO 10993-10”, and “ISO 10993-11”.

The material of the container wall may comprise a thermoplastic. In preferred aspects, the material of the container wall comprises a polyamide or a nylon, and more preferably polyamide 12 (PA 12) also known as Nylon 12. For example, the container wall may be made from “HP 3D High Reusability PA 12” as manufactured by Hewlett Packard. The coolant is a liquid sufficiently cold to freeze tumor cells. Thus, the coolant preferably has a freezing point below, and more preferably well below, negative sixty (-60) degrees Celsius. It can thus be ensured that the tumor(s) are frozen quickly.

Preferably, the coolant is liquid nitrogen. This ensures that there is a rapid freeze, and that the tumorous cells can be frozen to at least negative 20 degrees Celsius within a few minutes. A rapid freeze, followed by a slow thaw, is preferable for a more complete destruction of the tumorous cells. Preferably, the thawing time is at least twice as long as the freezing time. This enables water crystals to form in the tumor cells which in turn destroys said tumor cells.

The coolant can enter the container 102 through the coolant inlet 103 which provides fluid communication between a coolant source and the inside of the container 102. For example, the coolant inlet 103 is an aperture in an upper surface of the container wall through which the coolant may be poured into the container 102.

The shape of the container 102 is largely determined based on the anatomy of the patient. The shape may further be influenced by tumor shape and/or (supposed) positioning of the patient on the operation table. For example, the length of the container 102 may be determined in dependence on the length of the tumor (and/or a section of tissue surrounding/containing the tumor), so as to avoid unnecessarily freezing of adjacent healthy tissue. The width and height of the container 102 may be determined in dependence on the anatomy of the patient, and/or the volume of coolant needed to sufficiently freeze the tumor.

The cryoablation device 101 is configured to provide, in use, a direct contact between the coolant in the container 102 and a section of tissue containing (i.e. enclosing, surrounding and/or affected by) the tumor. The section of tissue containing the tumor may herewith be referred to as the tumor-containing section of the tissue. The direct contact between coolant and the tumor-containing section ensures a very high heat transfer there between. The tumorcontaining section of tissue, and in turn the tumor, can accordingly be frozen quickly. It is important to note that the coolant may not necessarily be in direct contact with the tumor (or tumor cells), but rather in direct contact with the tumor-containing section of the tissue. Hence, it is important to have a high heat transfer (and a large temperature difference between coolant and tissue) in order to rapidly freeze the tumor cells, in particular because the tissue surrounding the tumor, in the tumor-containing section of the tissue, may act as an insulator.

Preferably, during use of the cryoablation device 101 , the coolant is in direct contact with the tumor-containing section of the tissue for at least 2 minutes, more preferably at least 5 minutes, yet more preferably at least 10 minutes, and most preferably at least 15 minutes. Thus, a complete destruction of the tumor cells can be ensured. The cryoablation device 101 may comprise one or more sensors or probes, such as one or more temperature sensors, to measure the temperature of the tumor-containing section of the tissue. The cryoablation device 101 may, for example, be configured to indicate to the user when the tumor-containing section of the tissue is sufficiently cold.

At the end of the cryoablation process, the remaining coolant in the container 102 may be left to evaporate. This normally only takes a short amount of time, e.g. up to a few minutes.

The container wall further comprises at least one edge defining an opening 104 for allowing a direct contact between coolant in the container 102 and the tumor-containing section of the tissue. The shape and size of the opening 104 may be determined in dependence on the shape and size of the tumor and/or the shape and size of the tumor-containing section of the tissue.

Each opening 104 is surrounded by a flange 105. The flange 105 is provided on the edge of the opening 104 and protrudes from the container wall at the edge. The flange 105 preferably extends outwards from the container 102 on an external surface of the container wall. The flange 105 is shaped so as to conform to the tumor-containing section of the tissue. The flange 105 has a 3D shape, in other words, the shape of the flange 105 may be designed such that it conforms to the 3D contour of the tumor-containing section of the tissue. The flange 105 may thus be referred to as a tissue-conforming flange 105.

Further details of the opening(s) 104 and flange(s) 105 will be described more fully in relation to the examples shown in Figs. 3 to 9.

A method of producing the cryoablation device 101 , including the method of producing the opening 104 and the flange 105, will be described in more detail in relation to Fig. 2.

The width of the flange 105 is sufficiently large to hold the bonding member 106. The bonding member 106 is provided on a tissue-facing surface of the flange 105. When the cryoablation device 101 is placed in contact with the tumor-containing section of the tissue, the bonding member 106 is configured to fix (e.g. bond, attach) the flange 105 to the tumor-containing section of the tissue, and thereby seal a contact surface between the flange 105 and the tissue. Any leakage of coolant from the container 102 across the contact surface can thus be significantly reduced. In other words, the tumor-containing section of the tissue, together with the bonding member 106, ensures that the at least one opening 104 is substantially sealed (closed) so as to substantially close the container 102. This ensures that only a non-significant amount of coolant is allowed to leak from the container 102 onto adjacent healthy tissue outside of the container 102.

The bonding member 106 may comprise a water absorbent foam. The foam is preferably a polyurethane foam, such as Allevyn® as manufactured by Smith & Nephew. Preferably, the bonding member 106 has a thickness of up to 10 mm, more preferably up to 7 mm, and most preferably up to 5 mm.

The bonding member 106 may be attached to the flange 105 by an adhesive. The adhesive may, for example, be a sterile glue. For a bonding member 106 comprising a polyurethane foam, a preferable sterile glue is a tissue adhesive, for example comprising monomeric n-butyl- 2-cyanoacrylate, such as Histoacryl® as manufactured by B. Braun Surgical, S.A.

The inventor has realized that when the water absorbent foam has been introduced to water (e.g. wetted, soaked) and the wetted absorbent foam is placed against the tumor-containing section of the tissue, coolant in the container 102 will freeze the wetted absorbent foam (i.e. ice crystals will form). This will form a bond between the water absorbent foam and the tumorcontaining section of the tissue by means of moisture solidification. The effect is similar to a person licking an ice-cold lamp post with their (wet) tongue. The tongue will be securely attached to the lamp post, in a similar manner to the wetted foam being securely attached to the tumor-containing section of the tissue. Thus, the flange 105 is bonded to the tumor-containing section of the tissue.

Although the water absorbent foam may be porous and/or permeable to coolant, the bond formed by the water absorbent foam ensures that any leakage of coolant from the container

102 is significantly reduced.

After removal of the coolant, the water absorbent foam will thaw and accordingly the bond will be reversed.

The cryoablation device 101 may preferably comprise a funnel. The funnel may be attachable or insertable to the container 102 via the coolant inlet 103. The funnel 304 may alternatively be an integral part of the container 102. The funnel makes it easier and more convenient to pour coolant into the container 102, thus reducing the risk of spilling coolant on adjacent (potentially sensitive) tissue. Additionally, a tube may be provided between the coolant inlet

103 of the container 102 and the funnel. The tube may enable a funnel to be used even when the anatomy of the patient is such that there is not sufficient space for a funnel directly attached to the container 102. The tube may preferably be designed according to the anatomy of the patient, and/or be semi-rigid so as to allow for some flexibility in its placement.

The cryoablation device 101 may be patient specific. In other words, the cryoablation device 101 may be shaped and/or designed in dependence on the patient to be treated. This can be achieved by 3D printing of the device in dependence on the anatomy of the patient.

Fig. 2 shows a method of producing a cryoablation device 101 . In step 201 , a 3D scan of tissue containing the tumor is performed. The scan is performed by a non-invasive method. The non-invasive method may be an X-ray scan, a magnetic resonance imaging (MRI) scan, an ultrasound scan or the like. As a result of the scan, a 3D model of the tumor-containing section of the tissue may be obtained.

In step 203, a cryoablation device 101 with a container 102 is manufactured in dependence on the 3D scan (and/or the 3D model of the tumor-containing section of the tissue). The container 102 is manufactured to comprise a container wall with at least one opening 104 surrounded by a tissue-conforming flange 105. The container 102 may be manufactured by 3D printing. The shape of the container 102, the opening 104, and/or the flange 105 may be determined based on the shape, size, and/or location of the tumor and/or the tumor-containing section of the tissue. The cryoablation device 101 may be formed of one integral part, or several parts joint together.

In step 205, a water absorbent foam is attached to a tissue-facing surface of the flange 105.

In step 207, the water absorbent foam may be wetted (or soaked) with sterile water.

Furthermore, the cryoablation device 101 , and in particular the container 102 may be sterilized.

Two specific aspects of the cryoablation device 101 will be discussed further in relation to the following figures. In the first aspect, which can be seen in Figs. 3 to 6, the cryoablation device 101 is configured to enclose or surround the tumor-containing section of the tissue. In the second aspect, which can be seen in Figs. 7 to 9, the cryoablation device 101 is configured to cover the tumor-containing section of the tissue.

The first and second aspects of the cryoablation device 101 will, in the following figures, be described in relation to bone tissue and bone tumors. However, it will be readily appreciated that the same cryoablation device 101 can be used for tumors located in other tissues such as soft tissues (e.g. muscles).

Fig. 3 shows a simplified cryoablation device 101 according to the first aspect in an exploded perspective view.

The cryoablation device 101 according to the first aspect comprises a container 102 with a container wall formed of two parts: an upper part 301 , and a lower part 302. The two parts of the container wall can be placed around the bone section containing the tumor and joined together so as to enclose the tumor-containing bone section.

The upper part 301 comprises the coolant inlet 103 for receiving the coolant, e.g. by pouring the coolant into the container 102 through said coolant inlet 103. A funnel 304 is inserted in the coolant inlet 103 to facilitate the pouring of coolant into the container 102. The container 102 shown in Fig. 3 comprises two openings 104 that allow coolant in the container 102 to come into direct contact with the tumor-containing bone section. The two openings 104 in the container wall can accommodate the bone in which the tumor resides, such that the bone extends into, and possibly through, the container 102. The tumor-containing section of the tissue can thus be enclosed in the container 102, and in direct contact with the coolant during treatment.

Each opening 104 in the container wall is necessarily larger than the bone section to be placed therethrough (to accommodate said bone), but a space between the bone and the edge of the opening 104 is preferably minimized to allow a tight fit. This is beneficial for reducing leakage of coolant, and for stability of attachment of the cryoablation device 101 enclosing the bone. For example, a tight fit may assist in ensuring that the cryoablation device 101 is not accidentally rotated (relative to the bone) while preparing for the treatment, because the bone is rarely perfectly circular in cross-section.

Around each of the two openings 104 a flange 105 protrudes from the container wall. The flanges 105 conforms to the portion of bone extending through the openings 104. The flanges 105 extend in a substantially outward direction from the edges of the openings 104. The flanges 105 may be sufficiently rigid to allow the edges defining the openings 104 (and flanges 105) to be clamped around the bone.

In Fig. 3, the flanges 105 are shown in a simplified manner with a cylindrical shape. It will be appreciated that the shape of the flanges 105 does not have to be cylindrical, but rather will depend on the shape of the bone containing the tumor. This will be discussed and illustrated further in relation to Figs. 4 to 6.

There is also provided a bonding member on an internal surface (i.e. tissue-facing surface) of each of the flanges 105.

Each of the edges defining the openings 104, flanges 105, and bonding members 106 are split by the upper part 301 and the lower part 302 of the container wall, such that each part comprises substantially half of each edge of openings 104, substantially half of each flange 105, and substantially half of each bonding member 106. Thus, the container 102 may easily be formed by placing the two parts of the container wall around the bone while the bone is still in place in the body.

The container 102 may further comprise one or more rib portions 305. The rib portions 305 may be provided at an external edge of the lower part 302 or upper part 301 of the container 102. The rib portions 305 may, for example, be provided on one or more sides of the container 102 where no opening 104 is present. For example, as shown in Figs. 3a to 3c, the rib portions 305 may be provided on the two longitudinal sides of the lower part 302. In preferred aspects, the rib portions 305 may be provided along substantially the entire external edge of one of the parts of the container 102.

The rib portions 305 may be located on an outside portion of the lower part 302 such that the upper part 301 can be placed inside the pair of rib portions 305 when joining the upper part 301 and the lower part 302 (or vice versa). The rib portions 305 provide a guiding means when aligning the two parts and joining them together. The rib portions 305 may, on an inside surface comprise a sealing means, such as a rubber seal. The sealing means can thus reduce leakage through the joint of the two parts.

The upper part 301 and the lower part 302 of the container wall may further comprise one or more fastening means 303 for joining the upper part 301 and the lower part 302.

The fastening means 303 may comprise at least one pair of fastening plates provided on respective and corresponding portions of the upper part 301 and the lower part 302. For example, as shown in Fig. 3, four pairs of fastening plates may be provided. It will be appreciated that the number of fastening plates may be determined in dependence on the shape of the container 102 (which in turn is dependent on the anatomy of the patient and/or the location of the tumor). Each fastening plate may be provided with one or more through-holes. Screws and/or bolts can thus be used to fasten a respective pair of fastening plates.

The fastening means 303 may alternatively comprise one or more clamps, or any other means capable of clamping, joining, or fastening the two parts together.

Although the container 102 shown is formed as a regular elongated dome, it will be appreciated that the container 102 can be of any shape suitable for containing liquid and enclosing the tissue to be frozen.

The container 102 may further be shaped such that a major part of its volume is located in close proximity to the tumor cells and/or a side of the bone where the tumor cells are located. For example, if the tumor cells are predominantly formed on one (internal) side of the bone, the container 102 may be shaped such that most of its volume is located on that side of the bone.

Figs. 4a and 4b show a cryoablation device 101 according to the first aspect in a side view, and a top view respectively. The cryoablation device 101 shown in Figs. 4a and 4b is substantially similar to the cryoablation device 101 shown in Fig. 3, apart from the shape of the flanges 105.

As seen in Figs. 4a and 4b, the flanges 105 are shaped to conform to the bone section to be enclosed within the container 102. At least one of the flanges 105 may be angled to one side to accommodate a bone which is not entirely straight. At least one of the flanges 105 may additionally or alternatively be tapered (i.e. have an increasing or decreasing diameter) to accommodate a bone with a varying thickness. The flanges 105 may be non-circular, and it will be appreciated that their shape will be determined by the shape of the bone.

Figs. 5a to 5c show a cryoablation device 101 in use that encloses a tumor-containing section of the tissue. Fig. 5a shows a side view of the cryoablation device 101 in use. Fig. 5b shows a cross-section of the cryoablation device 101 in use. Fig. 5c shows a cross-section of one of the flanges 105.

As can be seen in Figs. 5a and 5b, the container 102 encloses a section of the bone 501 comprising the tumor 502. Thus, when coolant is poured into the container 102 via the coolant inlet 103, the tumor-containing section of the bone will be cooled, and eventually frozen, by the coolant. Furthermore, the bonding member 106, together with the flanges 105 (that are shaped according to the specific portion of the bone where they are located) ensures that the cryoablation device 101 stays firmly in place. The bonding member 106 also ensures a minimal leakage from the container 102 to adjacent (healthy) tissue.

As can be seen in the cross-section in Fig. 5c, the flange 105 closely conforms to the relevant section of the bone 501. This ensures that the cryoablation device 101 stays firmly in place, and also that leakage of coolant is reduced.

Fig. 6 shows an illustration of an alternatively shaped cryoablation device 101 according to the first aspect. It will be appreciated that the difference in shape arises because of the anatomy of the bone. Importantly, when producing a cryoablation device 101 according to aspects disclosed herein, the flanges 105 and openings 104 are shaped according to the shape of the bone.

Fig. 7 shows a cryoablation device 101 according to the second aspect. In the second aspect, the container 102 is configured to cover the tumor-containing section of the tissue. In other words, as opposed to the first aspect, the tumor-containing section of the tissue is not enclosed by the container 102 during use.

Because the container 102 of the second aspect is not configured to enclose the bone, the container 102 may be formed of one integral part, i.e. a single piece of container wall.

The container wall of the second aspect has at least one edge defining an opening 104 for providing direct contact between the coolant and the tumor-containing section of the tissue. During use, the flange 105 is placed against a surface of the tumor-containing section of the tissue such that the opening 104 covers, at least partially, the tumorous section of the tissue. The size and shape of the opening 104 may be determined based on the shape and size of the tumor, such that the opening 104 can cover the relevant section of the tumor-containing section of the tissue.

The flange 105 is formed at the edge of the opening 104 and extends outwards from the container wall. The flange 105 is shaped according to the surface of the tumor-containing section of the tissue.

Although not shown in Fig. 7, a bonding member is to be provided on a tissue-facing surface of the flange 105. The bonding member surrounds the opening 104 and may be shaped substantially similar to the flange 105.

The flange 105 may be provided with one or more extensions 701. The extensions 701 are structural protrusions that extend from the surface of the flange 105 opposite to the tissuefacing surface. Each extension 701 may be a protrusion from the flange that comprises a through-opening extending from a top surface of the protrusion 701 to the tissue-facing surface of the flange 105.

The extensions 701 allow attachment means to be inserted therethrough for additional attachment of the flange 105 to the tissue or bone. The attachment means 801 thus increase the stability of the attachment provided by the bonding member and ensures that the cryoablation device 101 is securely kept in place on the tumorous section of the tissue. The attachment means may be one or more screws for screwing the flange 105 to the bone. Alternatively, the attachment means may comprise one or more pins or Kirschner wires (k-wires) to be inserted through the extensions 701 so as to attach said pins or k-wires to the bone.

One or more of the extensions 701 may also serve as holding means for one or more probes. The probes may comprise one or more sensors, such as temperature sensors for measuring the temperature of the tissue surrounding the opening 104 of the cryoablation device 101. It is accordingly possible to monitor that the temperature of the surrounding tissue stays above a threshold temperature. Furthermore, the probes may be provided with a heating mechanism for keeping the healthy tissue outside of the opening 104 sufficiently warm so as not to destroy the cells. For example, the probes may be configured to heat the tissue using microwaves and/or radiofrequency waves. The extensions 701 ensures that the probes are inserted to a predetermined depth in the tissue and in a predetermined direction in the tissue.

The one or more probes may be connected to a processor that is configured to monitor the temperature of the surrounding healthy tissue using data from temperature sensors of the probe, and if the temperature goes below a threshold, the processor may be configured to initiate the heating mechanism of the probe. Fig. 8 shows a cryoablation device 101 in use. The cryoablation device 101 is placed onto the bone such that the opening 104 partially covers the tumor-containing section of the tissue. Thus, the flange 105 surrounds the tumor-containing section of tissue. A cryoablation device 101 according to the second aspect may be particularly advantageous for treatment of a tumor located inside a bone section with an irregular shape (such as the one shown). Because a cryoablation device 101 according to the first aspect may require a significant container volume to enclose the bone, it may be more convenient to use a cryoablation device 101 according to the second aspect which merely needs to cover the tumor-containing section of the tissue.

As can be seen in Fig. 8, the flange 105 is shaped to conform to the bone. The flange 105 is further bonded to the bone by the bonding member. The cryoablation device 101 shown also comprises a funnel 304 for facilitating pouring of coolant into the container 102.

Furthermore, two k-wires 801 have been inserted through respective two extensions 701 of the cryoablation device 101 and into the bone section. The two k-wires thus further increases the stability of the attachment of the cryoablation device 101 to the bone. There is also provided a probe 802 which has been inserted through a third extension 701 of the flange 105. The probe 802 is connected to a processor via electric wiring means 803.

Although the extensions 701 , the attachment means and the probes, have been described in relation to the second aspect, it will be appreciated that these features may be used in the first aspect as well. For example, the flange 105 in Figs. 3 to 6 may be provided with one or more extensions 701, through which attachment means (such as k-wires 801) and/or probes 802 may be inserted.

Fig. 9 shows an illustration of an alternatively shaped cryoablation device 101 according to the second aspect. The cryoablation device 101 is placed on top of a pelvis bone. Again, due to the shape of the pelvis bone, a cryoablation device 101 according to the second aspect is preferred because it does not need to enclose the bone. As can be seen, the features of the cryoablation device 101 are substantially similar to previously described cryoablation devices, although the opening 104 and flange 105 have been shaped according to the specific structure of the pelvis bone. Furthermore, the cryoablation device 101 is fastened to the bone using a plurality of screws 901. Although not shown in Fig. 9, a bonding member may be used to bond the flange 105 to the pelvis bone.

Although specific reference has been made to bone tumors and bone tissue, it will be appreciated that the cryoablation device 101 as disclosed herein is equally applicable to tumors located elsewhere in the body.

Throughout this specification, the word “may” is used in a permissive sense (i.e. meaning having the potential to), rather than in the mandatory sense (i.e. meaning must). As used throughout this specification, the singular forms “a”, “an”, and “the”, include plural referents unless explicitly indicated otherwise. Thus, for example, reference to “an” element includes a combination of two or more elements, notwithstanding use of other terms and phrases for one or more elements, such as “one or more” or “at least one”. The term “or” is, unless indicated otherwise, non-exclusive, i.e. encompassing both “and” and “or”. For example, the feature “A or B” includes feature “A”, feature “B” and feature “A and B”.

Unless otherwise indicated, statements that one value or action is “based on” and/or “in dependence on” another condition or value or action, encompass both instances in which the condition or value or action is the sole factor and instances where the condition or value or action is one factor among a plurality of factors.

Claims

CLAI MS

1. A device (101) for in-situ cryoablation therapy of a tumor in a tissue, the device comprising: a container (102) adapted to hold a coolant at a temperature of below negative 60 degrees Celsius, wherein: the container (102) is formed of a container wall such that the container wall defines a volume to enclose the coolant; and the container (102) comprises a coolant inlet (103) for receiving the coolant; wherein the container wall comprises at least one edge that defines at least one opening (104) in the container wall; wherein the at least one edge is provided with a flange (105) protruding from the containerwall, wherein the flange (105) has a 3D pre-determined shape that conforms to a tumor-containing section of the tissue, said 3D predetermined shape having being produced in dependence of either a generic anatomical 3D model or a patient specific 3D scan of the tumor-containing section of the tissue; said at least one openings (104) being configured to allow a coolant within said container (102) to come in direct contact with the tumor-containing section of the tissue; wherein a tissue-facing surface of the flange (105) is provided with a bonding member (106) for fixing the tissue-facing surface of the flange to the tumor-containing section of the tissue such that leakage of any coolant though said at least one openings (104) is essentially prevented when the device (101) is applied to the tumor-containing section of the tissue.

2. The device (101) according to claim 1 , wherein the bonding member (106) is further configured to seal a contact surface, between the tissue-facing surface of the flange (105) and the tumor-containing section of the tissue, that is formed when the flange (105) is placed onto the tumor-containing section of the tissue.

3. The device (101) according to claim 1 or 2, wherein the bonding member (106) comprises a water absorbent foam.

4. The device (101) according to claim 3, wherein the water-absorbent foam is a polyurethane foam.

5. The device (101) according to any preceding claim, wherein: the container (102) is configured to enclose the tumor-containing section of the tissue; and the at least one edge of the container wall is configured to surround an end portion of the tumor-containing section of the tissue.

6. The device (101) according to claim 5, wherein the a first edge of the at least one edges defining a first opening (104) of the at least one openings (104), and wherein the containerwall further comprises a second edge of the at least one edges defining a second opening (104) of the at least one openings (104); wherein the first edge is configured to surround a first end portion of the tumor-containing section of the tissue and the second edge is configured to surround a second end portion of the tumor-containing section of the tissue, such that a portion of the tumorcontaining section of the tissue between the first and second end portions is enclosed by the container (102) and extends between the first and second openings (104).

7. The device (101) according to claim 6, wherein the container wall comprises two parts, and wherein the device further comprises fastening means for joining the two parts together.

8. The device (101) according to any of claims 1 to 4, wherein the flange (105) is configured to be placed against the tumor-containing section of the tissue such that the tumorcontaining section of the tissue remains substantially outside of the container (102), and wherein the opening (104) defined by the edge of the container wall is configured to, at least partially, cover the tumor-containing section of the tissue.

9. The device (101) according to any preceding claim, wherein a surface of the flange (105) comprises at least one extension (701) configured to receive one or more of: an attachment means for attaching the device to the tissue, and a probe for measuring a temperature of the tissue.

10. The device (101) according to any preceding claim, wherein, in use, the opening (104) is sealed by the tumor-containing section of the tissue together with the bonding member.

11. The device (101) according to any preceding claim, wherein the device further comprises: at least one probe (802) comprising: a temperature sensor for measuring a temperature of the tissue; and a heating means for heating the tissue; and a processor configured to initiate the heating means in dependence on a temperature measured by the temperature sensor being below a threshold temperature.

12. A method of producing an in-situ cryoablation device (101) according to any preceding claim, the method comprising: performing a 3D scan of a tissue comprising one or more tumors in order to obtain a 3D model of the tissue; manufacturing, in dependence on the 3D model, a device with a container formed of a container wall comprising an edge that defines an opening in the container wall, wherein the edge is provided with a tissue-conforming flange; attaching a water absorbent foam to a tissue-facing surface of the tissue-conforming flange.

13. The method of claim 12, wherein the 3D scan is performed by a non-invasive method.

14. The method of claim 13, wherein the 3D scan is one or more of: an X-ray scan, a magnetic resonance imaging scan and an ultrasound scan.

15. The method of any of claims 12 to 14, wherein the method further comprises one or more of the steps of: wetting the water absorbent foam with sterile water; and sterilizing the container.