EP1648549A1

EP1648549A1 - A catheter for cerebral treatment with radioactive substances

Info

Publication number: EP1648549A1
Application number: EP03817747A
Authority: EP
Inventors: Arturo Chiti; Paolo Gaetani; Riccardo Rodriguez Y Baena
Original assignee: Humanitas Mirasole SpA
Current assignee: Humanitas Mirasole SpA
Priority date: 2003-07-29
Filing date: 2003-07-29
Publication date: 2006-04-26
Also published as: AU2003253284A1; WO2005011793A1

Abstract

The present finding relates to a catheter (1) for cerebral treatment with therapeutic radioactive substances including a proximal portion (2), an intermediate portion (3) and a distal portion (4), said distal portion (4) comprising an internal balloon (10) and an external balloon (11), characterised in that said internal (10) and external balloons (11) are made from a material which is impermeable to fluids. The invention also relates to a method for cerebral treatment with radioactive substances employing said catheter.

Description

DESCRIPTION "A CATHETER FOR CEREBRAL TREATMENT WITH RADIOACTIVE SUBSTANCES" [0001] . The present finding relates to a catheter for cerebral treatment with radioactive substances and a method for cerebral treatment with radioactive therapeutic substances employing said catheter. In particular, the finding relates to a catheter insertable at the level of the encephalon in places where there have been, even partial, neoplasia removals.

[0002] . Various types of catheters used during surgical therapy to deliver drugs locally or to drain areas of the human body of liquids or unwanted secretions are known. [0003] . A particular type of catheter is represented by catheters which are used at the level of the encephalon following tumour removal operations . In these situations , over the course of a craniotomy operation for the removal of neoplasia or for a dedicated operation, a catheter is inserted into the cavity which forms following said removal, directly into the partially removed neoplasia. The catheter will then be filled with a pharmacological substance such as for example a radiodrug or a chemotherapeutic agent, so as to allow local treatment, particularly targeted to the area attacked by the tumour. This area, however, can in fact contain residual tumour cells despite the removal of the tumour mass itself, which can give rise to new malignant proliferation.

[0004]. The U.S. patent US 5,429,582 describes a catheter of the type just indicated in which an inflatable balloon is inserted into a cavity in the encephalon created by the removal of a tumour mass and is connected through a tube to a reservoir implanted subcutaneously in the patients head. Following the filling of the reservoir with a syringe containing a treatment liquid, the balloon connected thereto is inflated until its external wall adheres to the wall of said cavity. In particular, the catheter can comprise a dual walled balloon which delimits an internal chamber and an external chamber connected to respective tubes and subcutaneous reservoirs. In this manner, the innermost balloon is filled with a radioactive treatment substance, whilst the outermost balloon is filled with a chemotherapeutic agent which can permeate through the membrane of the corresponding balloon to come into direct contact with the cerebral matter to be treated. [0005] . A catheter for cerebral infusion such as that just described however has some drawbacks.

[0006] . Firstly, in the case in which the patient is treated only with the radioactive substance, the use of a single balloon is envisaged fitted with a respective tube for connection to a suitable subcutaneous reservoir. It is understood that the balloon and the reservoir must be filled or emptied with extreme caution as there is the danger of breakage of their walls with the consequent dangerous leakage of radioactive substance into the surrounding tissues. Similarly, the same problem also occurs with the use of the second balloon containing the chemotherapeutic substances as the wall of said balloon must be permeable in order to allow treatment. [0007] . Furthermore, the subcutaneous reservoir, beyond complicating the structure of the entire catheter, is hazardous since it is at risk to the possibility of being subject to shocks or crushing which could induce pressures therein such as to break its wall . [0008] . The problem at the heart of the present invention is therefore that of devising a catheter for cerebral treatment which allows the treatment of cerebral areas from which a tumour, or part of it, has been removed with radioactive substances, in a safe and functional manner. Such a problem is solved by a catheter for cerebral treatment as stated in the independent claim which allows overcoming the above mentioned known art drawbacks and satisfies the needs just set out. [0009] . Further characteristics and advantages of the catheter for cerebral treatment according to the invention will be apparent in the following description of an example embodiment, given as a non limiting example, wherein: Figure 1 represents a schematic plan and sectional view of a catheter for cerebral treatment according to the invention; - Figure 2 represents a schematic view of a partial section of the cranium of a patient with the catheter of figure 1 inserted therein; Figure 3 represents a schematic view of a partial section of the cranium of a patient, with the catheter of figure 1 in operative conditions, inserted therein.

[0010] . By the number 1 in the figures is globally indicated a catheter for cerebral treatment extending along an axis X-X according to the invention.

[0011] . With particular reference to figure 1, the catheter 1 comprises a proximal section 2, an intermediate section 3, having a substantially cylindrical shape, and a distal section 4 having a substantially balloon-like shape.

[0012] . The proximal section 2 consists of two hollow cylinder coaxially arranged one around the other, so as to form two portions of two internal 5 and external 6 tubes having their respective lumens 7 and 8 open. The external tube 6 can be provided with a flange (not shown in the figures) turned towards the exterior of its lumen 8 having the function of allowing easy anchorage of the entire catheter 1 onto the skin on the cranium of the patient. In addition, said flange will allow easy gripping for the extraction of the catheter 1 once the treatment has finished, as will be better described below. [0013] . The proximal portion 2 further comprises a non return valve 9 located within the lumen 7 of the internal tube 5. The valve 9 is arranged in such a manner as to allow the admission of treatment fluid through the internal tubing 5 for example by means of a syringe 19 (shown schematically in figure 3) entirely conventional within the medical- surgical sector. Said valve 9 would prevent the treatment fluid from spontaneously discharging, or returning, once the syringe is retracted from the lumen 7. The same valve 9 however allows for the emptying of the treatment substance, as will be described below. In particular, the valve 9 can consist of a "duck bill" type valve. Alternatively, the lumen 7 can be simply provided with a septum, consisting of a material known in the sector, which readily reseals following the extraction of a syringe needle introduced therethrough in order to inject the treatment substance. [0014] . The intermediate portion 3 constitutes a longitudinal extension of the proximal section 2 of the catheter 1 along the axis X-X. Consequently, the intermediate portion 3 comprises an internal tube and an external tube each of them being the extension of internal tube 5 and external tube 6 of the proximal portion 2. [0015]. The distal portion 4, as already mentioned, has the appearance of a kind of sheath or bag comprising an internal balloon 10 enclosed within an external balloon 11. In particular, the internal balloon 10 joins with the internal tube 5 of the proximal 2 and intermediate 3 portions so as to form an end container or chamber 12 and, hence, in such a way as to make the lumen 7 of said internal tube 5 communicate with said chamber 12 of said internal balloon 10. Similarly, the external balloon 11 joins with the external tube 6 so as to form an end chamber 13 and, hence, in such a way as to make the lumen 8 of said external tube 6 communicate with said chamber 13 of said external balloon 11. [0016] . The proximal 2 and intermediate 3 portions are made of a sufficiently rigid plastic material so as to not allow, above all, the lumen 7 of the internal tube 5 to collapse during the entire treatment period until the removal of the catheter 1 from the cranium of the patient . The plastic material can be therefore any of the materials normally used in the sector for the manufacture of catheters, such as for example nylon, polyethylene, polyurethane, PET or the like. It is to be noted that the external tube 6 can also be of a flexible plastic material in that, as will be better described below, its lumen must allow the entry of air in the initial step of implanting the catheter 1 and the later discharge of at least a part of said air when under pressure. In the case in which rigid materials are also used for the external tube 6, then either a circular ring (not shown) which closes the lumen 8 except at one point in order to allow the admission or the discharge of the air, or an analogous system which works in the same manner can be provided. Alternatively, a circular non-return valve can be provided such as for example the aforementioned "duck bill" valve. [0017] . With reference, instead, to the distal portion 4, the internal 10 and external 11 balloons are made of an elastic, or at least flexible, plastic material, since it must allow the expansion of the balloons following their filling up with air or treatment fluid and their return to the relaxed state following their emptying. Furthermore, it is fundamental that this material be impermeable to fluids and, in particular, to gas with reference to at least the external balloon 11. In fact, the internal balloon 10 is filled with a radioactive treatment substance such as for example a radionuclide, generally in liquid solution. It is understood that such a substance must absolutely not be able to permeate out from the internal balloon 10. Consequently, its material must be impermeable to liquids, preferably also impermeable to gas. In any case, the external balloon 11 must be made from a material that is also impermeable to gas in such a way as to create a safety cover around the internal balloon 10 which contains the treatment substance. Materials which meet the above mentioned requirements can be for example latex, latex-similar, flexible siliconised plastic and the like. [0018] . The proximal 2 and intermediate 3 portions can have lengths between 10 cm and 20 cm, preferably the length is 11.5 cm, whilst the diameter of the internal lumen 7 and the external lumen 8 are between 1.5 mm and 3 mm and between 0.5 mm and 1 mm, respectively. The external diameters of the internal 10 and external 11 balloons are between 0.5 cm and 4 cm, under filled conditions . [0019] . According to a variant embodiment of the invention (not shown) , the catheter 1 can have the internal 5 and external 6 tubes arranged side by side, i.e. not coaxial, with the respective independent lumens 7 and 8. In such a way the proximal section 2 will comprise two distinct tubes one of which will join with an internal balloon and the other with an external balloon just as described above. In this case, it is possible to arrange a non-return valve, such as that described above, also within the lumen of the tube through which the air which fills the external balloon passes . [0020] . Preferably, in addition, the proximal portion 2 protrudes from the cranium of the patient once the catheter is inserted into the encephalon for therapeutic treatment of at least 2-3 cm in order to facilitate the operations of the admission of air to the inside of the external balloon 11 and the therapeutic substance to the inside of the internal balloon 10.

[0021]. The proximal 2, intermediate 3 and distal 4 portions can be made in one piece creating a single unit with appropriate adaptations at the level of the tubes so as to avoid the collapse of the respective lumens. For example, said sections can be made of the same elastic plastic material in a single piece with the addition of sufficiently rigid sleeves applied to the walls of the lumens of the tubes so as to keep them open. Alternatively, if different materials are used for different portions, then the materials can be sealingly joined together by for example, melting or gluing with biocompatible glues.

[0022] . The catheter subject of the present invention can advantageously comprise a closing (not shown) of the end of the proximal portion 2. This closing can be, for example, a stopper which fits the coaxial shape of the internal 5 and external 6 tubes or a stopper for each tube in the case in which these have separate lumens. It is understood that this way avoids the possibility that impurities can deposit themselves within the lumen of the tubes when repeated treatments are required. [0023] . According to an additional object of the invention, the working of the catheter 1 as well as a method of cerebral treatment with therapeutic radioactive substances using said catheter will now be described. [0024] . A cranioto y operation for the removal of neoplasia is carried out by firstly lifting an area 14 of the skin from the head of a patient and making a hole 18 in the bone of the cranium allowing access to the encephalon 15 at the level of the neoplasia (figure 2) . At this point the tumour mass is identified and removed which will leave a "virtual" cavity 16. This cavity may contain remains from tumour cells on its wall 17 which have not been removed together with the identified tumour mass or macroscopic residues of the partially removed neoplasia. Following this operation it is hence possible to insert a catheter 1, such as that described above for treating residual neoplasia, into the cavity.

[0025] . The insertion of the catheter 1 into the cavity 16 left by the removal of the neoplasia occurs by simply introducing the catheter 1 into the hole 18 made in the cranium from the side of the distal portion 4, until the latter reaches the abovementioned cavity (figure 2) . Obviously, the proximal section 4 will have the internal 10 and external 11 balloons released in order to cause minimum hindrance during insertion. At this point, as represented in figure 3 , the external balloon 11 is inflated with air by means of a syringe 19 inserted into the lumen 8 of the external tube 6 so that its external wall is substantially in contact with the wall 17 of the cavity 16. Subsequently, the treatment substance or radionuclide is injected into the internal balloon 10 through the internal tube 5 by means of an additional syringe 20, so as to inflate the internal balloon 10. [0026] . It is understood that when the internal balloon 10 is inflated with the radionuclide in solution, the balloon itself expands and compresses the air contained within the external balloon 11. In turn, the external balloon 11 tends to react to such pressure by expanding further and then tending to exercise pressure on the wall 17 of the cavity 16. At this point, in order to avoid a dangerous increase in pressure on the wall of the cavity, the piston of the syringe 19 is left free to move outwards in such a manner that the syringe can act as a means of deflation for the air contained within the external balloon 11 and compressed by the expansion of the internal balloon 10. Alternatively, said means of deflation can themselves be represented by a "duck bill" type valve having the respective laps arranged into a circular ring. In this manner, the air can be deflated by simply pressing on the external walls of the proximal portion 2. [0027] . The internal balloon 10 is filled with a radionuclide suitable for such types of treatments, until its external wall come into contact with the internal wall of the external balloon 11. In other words, the catheter 1 of the invention works through two chambers, one inside the other, which are inflated, in succession from the outer to the inner, with air and with a liquid solution containing a radionuclide, respectively, in such a away as to form a single dual walled chamber which substantially adheres to the internal wall of the cavity. This way, the treatment substance finds itself substantially in contact with the area to be treated thus favouring its effectiveness against the residual tumour cells. Advantageously, moreover, the treatment substance, or the radionuclide, finds itself inside an impermeable dual walled chamber. It is understood therefore that the catheter 1 according to the invention is much safer with respect to prior art catheters which use a radioactive substance as the treatment substance.

[0028] . Once the internal balloon 10 has been filled as just explained, the syringes 19 and 20 are retracted from the respective tubes and the catheter 1 is fixed onto the skin of the patient through suture stitches at the level of the previously described flange. In addition, if desired, the end of the proximal portion 4 can be closed with a suitable stopper. [0029] . When the radionuclide has finished its therapeutic effect, it is simply sufficient to again insert a syringe inside the lumen 7 of the tube 5 of the catheter 1 so as to separate the laps of the "duck bill" valve 7 and suck up the solution containing the radionuclide. At this point, the internal 10 and external 11 balloons will deflate and, after having removed the stitches which anchor the flange of the catheter 1 to the patient's skin, it is possible to slip the catheter 1 from the treated cavity by acting on said flange. [0030] . From what described up to now, the method of cerebral treatment with radioactive substances and also the working of the catheter just described are therefore safe and above all relieve the physician from the burden of complex and risky operations such as these that can be necessary when a catheter such as that described in the U.S. patent US 5,429,582 is used as reported in the introductory section of the present description.

[0031] . In fact, the catheter described in said patent provides the use of a subcutaneous reservoir which serves as an intermediate between the operator and the balloon containing the treatment substance. The operator is thus forced to act with extreme precision and control on the reservoir by means of a needle of a syringe. The operator must first of all insert the needle underneath the skin of the patient in a very delicate manner to give as little discomfort as possible to the patient, and in addition, he must appreciate however that the subcutaneous reservoir has limited thickness. [0032] . In addition, the structure of the catheter in the U.S. patent is a rather complicated since it provides the above mentioned subcutaneous reservoirs, which are by no means necessary in the present invention. Once the treatment is terminated, in fact, these reservoirs must also be removed, but their removal can occur only following incision of the skin and its raising in order to be able to gain access to the reservoir. Subsequently, the skin must be sewn up again. It is understood therefore that additional surgical operations are required. [0033] . Finally, as already mentioned above, the catheter according to the U.S. patent does not describe, nor suggest, the use of a second chamber or safety wall against accidental breakage of, and leakage of radioactive substance from, the balloon which contains it . [0034] . With reference to the method of cerebral treatment with a radioactive substance, from that described, it emerges that the embodied operations are advantageously simplified with respect to any of the methods of the known art. It follows, once again, that the safety of the operations is notably increased. [0035] . A number of variants of the catheter for cerebral infusions as well as the method of infusion according to the present invention can nevertheless be made by the expert in the art, without however departing from the scope of protection of the following claims .

Claims

1. A catheter (1) for cerebral treatment with therapeutic radioactive substances which includes a proximal portion (2) , an intermediate portion (3) and a distal portion (4) , said distal portion (4) comprising an internal balloon (10) and an external balloon (11) , characterised in that said internal (10) and external balloons (11) are made from a material which is impermeable to fluids.

2. The catheter (1) according to claim 1, wherein said material is impermeable to gas.

3. The catheter (1) according to claims 1 or 2, wherein said material is selected from latex, similar-latex, flexible siliconised plastic and the like.

4. The catheter (1) according to claims 1, 2 or 3, wherein said proximal portion (2) comprises an internal tube (5) and an external tube (6) which are arranged coaxially and have respective internal (7) and external (8) lumens.

5. The catheter (1) according to any of the claims 1 to 4, wherein said proximal portion (2) comprises an internal tube (5) and an external tube (6) arranged substantially side by side in such a way as to have respective independent lumens .

6. The catheter (1) according to any of the claims 1 to 5, wherein said internal tube (5) comprises a non return valve (9) inside its lumen (7) .

7. The catheter (1) according to any of the claims 1 to 5, wherein said internal tube (5) comprises a sealing septum inside its lumen (7) .

8. The catheter according to claim 6, wherein said non return valve (9) is a "duck bill" type valve.

9. The catheter (1) according to any of the claims 1 to 8, wherein said proximal portion (2) protrudes from the cranium of the patient by at least 2-3 cm once the catheter (1) is inserted.

10. The catheter (1) according to any of the claims 1 to 9, wherein said proximal (2) and intermediate (3) portions are made from materials selected from nylon, polyethylene, polyurethane, PET and the like, latex, similar-latex, siliconised plastic and the like.

11. The catheter (1) according to claim 10, wherein when said material is selected from latex, similar-latex, siliconised plastic and the like, the corresponding internal (7) and external lumens (8) of the internal (5) and external tubes (6) can be provided with sleeves made of materials selected from nylon, polyethylene, polyurethane, PET and the like.

12. The catheter (1) according to any of the claims 1 to 11, wherein the proximal (2) and intermediate portions (3) have a length comprised of between 10 cm and 20 cm.

13. The catheter (1) according to any of the claims 4 to 12, wherein the internal diameter of the internal lumen (7) and the external lumen (8) are between 1.5 mm and 3 mm and between 0.5 mm and 1 mm, respectively.

14. The catheter (1) according to any of the claims 1 to 13, wherein the external diameters of the internal (10) and external balloons (11) is between 1 and 3 cm.

15. The catheter (1) according to any of the claims 1 to 14, comprising a flange suitable for fixing the catheter to the patient' s skin.

16. The catheter (1) according to any of the claims 1 to 15, further comprising a reversible closure at the end of the proximal portion (2) .

17. A method of cerebral treatment with a therapeutic radioactive substance comprising the following steps in sequence: - providing a catheter (1) for cerebral treatment according to any of the claims 1 to 14; inserting said catheter (1) into a cerebral cavity (16) ; inflating the internal balloon (11) with air until its external wall comes substantially into contact with the wall (17) of said cavity (16) ; inflating the internal balloon (10) of said catheter (1) with a radioactive treatment substance until its external wall comes substantially into contact with the internal wall of the external balloon (11) , the pressurized air inside the external balloon (10) being vented through venting means (19) .

18. The method according to claim 17, comprising the step of releasably fixing said catheter (1) to the patient's skin.

19. The method according to claims 17 or 18, wherein the steps of inflating the internal (10) and external balloon (11) respectively are performed by means of syringes (19) and (20) .

20. The method according to claims 17, 18 or 19, wherein said venting means comprise the cylinder of a syringe (19) .

21. The method according to any of the claims 18 to 20 wherein said stage of releasably fixing the catheter (1) to the patient's skin is performed through the application of surgical stitches between said skin and a flange of said catheter.

22. The method according to any of the claims 17 to 21, comprising a deflation step of the internal balloon (10) once the treatment is finished.

23. The method according to claim 22, wherein said deflation step comprises the insertion of a syringe inside the lumen

(7) of the internal tube (5) of the catheter (1) and the aspiration of the treatment substance.

24. The method according to claim 22, comprising in addition the disengagement of the catheter (1) from the patient's skin and the slipping of said catheter out from within the patient' s cranium.

25. The method according to claim 24, wherein said disengagement is performed by cutting said suture stitches and slipping the catheter (1) from the cranium of the patient by acting on the aforementioned flange.