Patient-specific intraluminal device fitting

Abstract

A method of selecting an intraluminal device. The method is carried out by determining a diameter compatibility of a segment of a hollow organ of a subject and selecting a size of the intraluminal device based on the diameter compatibility of the segment of the hollow organ.

Description

[0001] PATIENT-SPECIFIC INTRALUMINAL DEVICE FITTING

[0002] RELATED APPLICATION / S

[0003] This application claims the benefit of priority of U.S Provisional Patent Application No. 63 / 528,936, filed on July 26, 2023, the contents of which are incorporated herein by reference in their entirety.

[0004] BACKGROUND

[0005] The present invention relates to a method of selecting a patient- specific intraluminal device based on compliance and / or colon diameter of the patient.

[0006] The colon is a compliant organ designed to expand and contract to absorb water and move food through the gastrointestinal tract. In patients with colorectal cancer (CRC), the compliance of colon tissue can be altered by disease, or factors related to the treatment of the disease such as chemotherapy or radiation therapy.

[0007] Changes in colon compliance in CRC patients affect the ability of colon tissue to stretch which can lead to anastomotic tension post-operatively and a reduction in the efficacy of intraluminal bypass devices due to poor fitting.

[0008] There is thus a need for, and it would be highly advantageous to have, an approach for accurately fitting an intraluminal bypass device to a CRC patient post resection surgery.

[0009] SUMMARY

[0010] According to one aspect of the present invention there is provided a method of selecting an intraluminal device for implantation in a subject comprising determining a diameter of a segment of a hollow organ of a subject; and selecting a size of the intraluminal device based on the diameter of the segment of the hollow organ.

[0011] According to embodiments of the present invention the hollow organ is a colon and the segment is an excised segment of the colon.

[0012] According to embodiments of the present invention determining a diameter is carried out by inflating a balloon within the excised segment of the colon and monitoring pressure in the balloon.

[0013] According to embodiments of the present invention the balloon is inflated to a known volume. According to embodiments of the present invention a pressure reading in the balloon is indicative of a suitability of an intraluminal device having a known diameter to implantation in the subject.

[0014] According to embodiments of the present invention the balloon is inflated to a known diameter of a selected implant and if a pressure reading in the balloon is higher than zero and less than 40 mmHg, the selected implant is suitable for implantation in the subject.

[0015] According to embodiments of the present invention the intraluminal device includes anchoring balloons and selecting the size of the intraluminal device is selecting a diameter of the anchoring balloons.

[0016] According to embodiments of the present invention the excised segment of the colon is obtained from a colon resection surgery of the subject.

[0017] According to embodiments of the present invention the colon implant size is selected for the subject.

[0018] According to embodiments of the present invention the method further comprises determining a compliance of the segment of the hollow organ of the subject.

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

[0020] BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0021] The invention is herein described, 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 discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.

[0022] In the drawings: FIG. 1 illustrates an approach for measuring compliance and size of colon tissue.

[0023] FIG. 2 is a graph of volume vs diameter that can be used for determining the device size suitable for implantation in a subject.

[0024] FIG. 3 is a table summarizing the results of the present study on colon tissue using ex- vivo compliance measurements.

[0025] FIG. 4 is a graph of the compliance data acquired by the present study as compared to prior art in-vivo measurements.

[0026] DETAILED DESCRIPTION

[0027] The present invention is of an approach which can be used for correctly fitting an intraluminal device to a CRC patient post colon resection.

[0028] The principles and operation of the present invention may be better understood with reference to the drawings and accompanying descriptions.

[0029] Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

[0030] Intraluminal bypass devices used in the colon post anastomosis are typically of a one size fits all configuration. Experiments conducted by the present inventors have shown that there is a need for patient-device size matching and that such matching requires actual measurements of colon compliance and diameter.

[0031] Thus, according to one aspect of the present invention there is provided a method of fitting an intraluminal device to a subject. The intraluminal device can be an anastomosis bypass device positionable in a hollow organ such as a colon. One example of such a device is described in US08690817B2.

[0032] Fitting the device can be carried out by determining a diameter (and optionally compliance) of the hollow organ, e.g., a segment of a colon of a subject using an ex-vivo approach (although an in-vivo approach can also be used). Once the diameter (and optionally compliance) is determined, a device of an appropriate size is selected and implanted using a standard appraoch.

[0033] In the case of a colon- specific intraluminal device, delivery can be carried out following any anastomosis procedure which requires leakage protection. In a standard colorectal anastomosis procedure, a section of the colon is resected and the 2 remaining healthy section of the colon are prepared for reconnection. Colon anastomoses are usually performed using surgical staplers but sutures can be also used to perform the anastomosis. When using the stapling technique, A stapler anvil is inserted into the proximal section of the colon and the stapler is inserted through the anal orifice and advanced into the distal stump of the colon, the stapler is then connected to the anvil. The stapler is fired to create the anastomosis and then removed through the anal orifice. A catheter is then advanced through the anal orifice and used to inflate the anastomosed colon with air, gas or a saline solution in order to check for leaks at the anastomosis site. A delivery catheter carrying an intraluminal device is then inserted through the anal orifice and positioned with its distal end above the anastomosis site. The device is then deployed and anchored in position using anchoring balloons, sutures, staples and the like.

[0034] Measuring a diameter of a colon segment can be carried out using an ex-vivo approach (on the resected colon segment) or using an in-vivo approach although the latter approach is less preferred due to the need for opening the colon intra-operatively thus increasing the risk for infections

[0035] In the ex-vivo approach, the excised colon segment is measured using a dedicated system. The system includes a balloon catheter fitted with a balloon having a maximal inflation diameter that is much larger than a typical colon diameter (e.g., 60 -100 mm). The balloon can be an elastic balloon in which case the balloon can be pressurized and stretched to over 50 mm in diameter or a sac-like, non-elastic balloon that can be inflated to over 50 mm in diameter but not pressurized. The system is first calibrated by inflating the balloon in a series of rigid tubes having varying diameters. When using a compliant (elastic) balloon, the pressure in the balloon changes (spikes) when it contacts the inner walls of the rigid tubes thereby providing a pressure change reading that corresponds to the inner diameter of each of the rigid tubes. When using a sac-like balloon, contact with the tube results in a pressure reading (above zero). A volume / pressure-diameter relationship can then be used to generate a graph that enables extrapolation of diameter based on a volume used to inflate the balloon.

[0036] The balloon can be introduced into the excised colon segment and then inflated to a first volume that corresponds to a known intraluminal device diameter. A safe pressure threshold (e.g., up to 40 mmHg) can be used to determine if the colon can safely accommodate this specific intraluminal bypass device size. If the pressure reading is way below the safe pressure threshold, the balloon can be inflated to a second volume that corresponds to a second known intraluminal device diameter. These steps are repeated until a correct device size is selected for the patient. When using an elastic balloon, compliance of the colon tissue can be determined by recording a first pressure change at contact and a second pressure change at diameter limit of colon. These numbers can be used to calculate how much a colon segment can stretch under inflation. The compliance of a colon segment can be used, for example, to determine the pressure used in the anchoring balloons of the implanted device (e.g., the device described in US08690817B2)

[0037] The in-vivo approach can be carried out using similar methodology.

[0038] Referring now to the drawings, Figure 1 illustrates a system for measuring colon diameter and / compliance which is referred to herein as system 10.

[0039] System 10 includes a catheter 12 having a distal end fitted with a balloon 14. Balloon 14 can be fabricated from an elastic or no-elastic material (e.g., silicone or medical grade polyvinyl chloride (PVC) that is capable of inflating to a maximal diameter of over 50 mm, and a pressure of 100 - 400 mmHg prior to rupturing (via air, saline or water). Balloon 14 can have a maximum volume of 350 ml and a length of 70 mm or more.

[0040] Catheter 12 includes an inflation port 16 opening to inner lumen 18 that is in fluid communication with an internal volume of balloon 14. Inner lumen 18 is also connected to a pressure gauge 20 for measuring the pressure within system 10. Inflation port is connected to a pressure source (pump / syringe).

[0041] Balloon 14 is positioned within the colon segment (CS) and gradually inflated to one or more known diameter points (e.g., 36, 48, mm) based on a known volume-diameter relationship established using a series of rigid tubes (see Examples section). Pressure gauge 20 is monitored during inflation and once the balloon is inflated to the predefined diameter (based on volume) the pressure is recorded. The user matches the recorded (non-zero) pressure with a predefined safe pressure threshold (e.g., 36-40 mmHg) to decide which intraluminal device size should be used for the specific patient. The recorded pressure represents the point of contact between the balloon and colon inner wall. In the case of a sac-like balloon, contact raises the pressure within the balloon to above zero.

[0042] For example, a colon (segment) with an unstretched diameter of about 32-34 mm and a high tissue compliance would produce a lower balloon contact pressure at an inflation volume that equals to a diameter of 39 mm. If the 39 mm contact pressure measure is way lower than 40 mmHg that may indicate a need to test the contact pressure at a 46 mm balloon diameter. If the pressure at the latter diameter is below 40 mmHg and above a non-zero pressure (e.g., 4-8 mmHg), the selected device for that specific patient should then be the 46 mm diameter device. As used herein the term “about” refers to ± 10 %.

[0043] Additional objects, advantages, and novel features of the present invention will become apparent to one ordinarily skilled in the art upon examination of the following examples, which are not intended to be limiting.

[0044] EXAMPLE

[0045] Reference is now made to the following example, which together with the above descriptions, illustrate the invention in a non-limiting fashion.

[0046] Ex-Vivo Colon Sizing

[0047] An ex-vivo experiment (non-interventional) is conducted in order to measure colon compliance. The study employs a Barostat balloon kit for recording colon pressure vs. diameter in freshly harvested colon specimen excised from colorectal cancer patients. Following testing, the tissue is sent for pathological assessment per routine practice.

[0048] Materials and Methods

[0049] Fifteen patients underwent mechanical bowel preparation and received antibiotic prophylactic treatment and anticoagulation treatment per routine clinical practice at the hospital. The patients underwent elective laparoscopic colorectal resection.

[0050] Following the colon resection, the tissue specimen of each patient was mechanically tested by a trained Clinical Application Specialist using a Barostat test kit.

[0051] The Barostat Kit includes four components: a barostat balloon, a pressure gauge, a 3-way stop cock and a 20 mL Syringe. The colon tissue was inflated to a specified diameter using the barostat balloon, and in each diameter the applied pressure on the colon wall was measured. A maximal pressure of 80 mmHg is defined and will not be exceeded. This test was performed on the excised tissue, about 10-15 cm proximal to the area of the tumor. The measurements lasted a few minutes and were done in parallel to the surgery which continues as planned with no delay. Following testing, the tissue was sent for pathological assessment per routine practice.

[0052] Results

[0053] Measurements were successfully performed in all 15 specimens. No complication or deficiency noted with the measurement method. A summary of the results is shown in Figure 3.

[0054] The compliance data that was acquired by the present study was compared with prior art in-vivo measurements (Figure 4). As is shown in Figure 4, the compliance curves acquired ex- vivo in the CRC population overlaps with the range of the curves that were generated from the Mayo clinic dataset. The fact that the overlapping appears to be mostly in the lower range might be explained by the differences between the 2 patient populations (CRC patients vs healthy / constipated / IBS patients). This side-by-side comparison demonstrates an overlap in the datasets which proves that the ex- vivo measurement of colon compliance is not only feasible but also represents values measured in-vivo, thus confirming the present ex-vivo approach a simpler non-interventional alternative to in-vivo approaches.

[0055] The data acquired by the present study was then used to select a correct size of an intraluminal device (Colospan) for each patient. The original Colospan device was offered in a single size designed to dilate colons in the range of 25-34 mm to 46 mm following deployment. Previous clinical data raised the need for patient-specific device size selection which requires additional device sizes (a smaller designed to dilate the colon to 39 mm was added) and intraoperative assessment of colon compliance to account for the variability in patients.

[0056] The above-described colon compliance measurements were used as a basis for device selection.

[0057] Out of the fifteen specimens tested, fourteen specimens were within the diameter range intended for use (25 to 32 mm), and one specimen (01-01) had a resting diameter of 22 mm and is not within the intended use of the device and was not considered in the analyses.

[0058] The safety threshold for the mucosal tissue lining the colon chosen was 36 mmHg and is based on a comprehensive literature search in endotracheal tubes which is the most similar clinical application found, and human colon distention under different pressure. 36 mmHg is achieved by adding the initial pressure required to overcome the initial collapse of the colon and reach a stress-free diameter (14 mmHg5) to the maximum safe pressure load of 22 mmHg.

[0059] Of the fourteen specimens that lie within the intended colon range (25 to 32 mm), and who would have qualified to receive a device under the previous study plan, there were four instances (01-06, 01-09, 02-03 and 01-12) where the pressure that was measured exceeded the safety pressure threshold of 36 mmHg when the colon was dilated to the designated diameter of 39 mm. In these four cases, the barostat measurement may indicate a low tissue quality.

[0060] The maximal safety pressure for each balloon size was set to around 36 mmHg, above that a smaller device size was selected or patient was excluded from implantation. Thus, a selected size should fall below the 36 mmHg pressure to be suitable for implantation in a specific patient.

[0061] Conclusion

[0062] The data acquired in this study proves that the measurements can be collected effectively, and that the outcomes are consistent with measurements that were done in-vivo. The present study also demonstrates that correct sizing of an intraluminal device based on ex-vivo data is a viable and simple approach that can substantially reduce device-related failures.

[0063] The data collected in this study points to a significant 61% decrease (p=0.0003) in pressure when the colon was dilated to 39 mm versus 46 mm, which indicates that that the introduction of a smaller Colospan device for smaller colon diameters will reduce the pressure on the colon. Furthermore, implementing the proposed method as a standard test to evaluate the quality of tissue can alert the surgeon to those patients whose are less likely to tolerate dilation to the desired colon diameter.

[0064] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.

[0065] Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

[0066] It is the intent of the applicant(s) that all publications, patents and patent applications referred to in this specification are to be incorporated in their entirety by reference into the specification, as if each individual publication, patent or patent application was specifically and individually noted when referenced that it is to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting. In addition, any priority document(s) of this application is / are hereby incorporated herein by reference in its / their entirety.

Claims

WHAT IS CLAIMED IS:

1. A method of selecting an intraluminal device for implantation in a subject comprising:(a) determining a diameter of a segment of a hollow organ of a subject; and(b) selecting a size of the intraluminal device based on said diameter of said segment of said hollow organ.

2. The method of claim 1, wherein said hollow organ is a colon and said segment is an excised segment of said colon.

3. The method of claim 2, wherein (a) is carried out by inflating a balloon within said excised segment of said colon and monitoring pressure in said balloon.

4. The method of claim 3, wherein said balloon is inflated to a known volume.

5. The method of claim 4, wherein a pressure reading in said balloon is indicative of a suitability of an intraluminal device having a known diameter to implantation in the subject.

6. The method of claim 5, wherein said balloon is inflated to a known diameter of a selected implant and if a pressure reading in said balloon is higher than zero and less than 40 mmHg, said selected implant is suitable for implantation in the subject.

7. The method of claim 1, wherein the intraluminal device includes anchoring balloons and selecting said size of the intraluminal device is selecting a diameter of said anchoring balloons.

8. The method of claim 2, wherein said excised segment of said colon is obtained from a colon resection surgery of said subject.

9. The method of claim 8, wherein the colon implant size is selected for said subject.

10. The method of claim 1, further comprising determining a compliance of said segment of said hollow organ of said subject.

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