JPH01170473A - Method for treating intracorporeal tumor and catheter apparatus for treating the same - Google Patents

Abstract

PURPOSE: To cure tumor existing in a patient's body, by equipping two catheters with wide range of operability placed coaxially and other members of pump, filter, analyzing instrument, and a means to regulate flow quantity coming out of tumor. CONSTITUTION: A first feed back loop, i.e., the passage for a curative medicine, is formed by drawing back of the chemical curative agent by a manual pump injector 36 from a port 34 to the inside of a suction catheter 35. The chemical curative agent is filtered and repeatedly reinjected to a tumor blood vessel through an injector 26 and a port 25. Formation of a second feed back group is carried out by forcibly injecting medicine such as the chemical curative agent, etc., upstream into the vein 50 and advancing the medicine such as a chemical curative agent toward the manual pump injector 36 along a path formed by expanded balloon 22 and 38 of catheters 18 and 35 via a V-V side passage. The injector 36 acts to draw the medicine from a port 34 to analyze and filter.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a method and apparatus for treating diseases or immune deficiencies, and more particularly to a method and apparatus for treating tumors present in a patient's body. It is.

(Technical Background) In the treatment of solid tumors, it has been conventional practice to inject chemotherapeutic agents into arteries. This is a unidirectional process that involves a single pathway, with the drug passing through the tumor via the arterial side of the body. First of this method
The disadvantage of this is that, as toxic elements circulate throughout the tissues and organs of the body, it is not possible to ensure the dosage and/or duration of action of the drug required to achieve the drug's effect. . That is, in the current methods of treating solid tumors using chemotherapeutic agents, the effectiveness of the treatment is diminished due to leakage of harmful chemotherapeutic agents to other parts of the human body.

Normal blood flow originates in the heart, flows through arteries, then through capillaries and into veins. The walls of postcapillary venules, capillaries, and sinusoids are exchange vessels that serve as exchange sites between blood and tissue fluid that bathes the cells. Venules and veins, which are larger than the blood vessels, contain a system of reservoirs that pool blood. These are large volume, low pressure blood vessels through which blood is returned to the right side of the heart.

Under normal conditions, the endothelial cells that form the lining of the vascular network shed and regenerate themselves at an extremely slow rate.
w) Folkr Takaan says, “Tumor angiogenesis”
(Scientific American, June
, 1976 (p. 71)), ``When needed to heal a wound or confer an immunogenic effect,...
Parts of the vasculature often grow explosively for short periods of time. However, new blood vessels always return after a short time and undergo regenerative activity.
ty) settles to its previous low state. "It has said. Cells are needed for immunity to heal wounds,
Proliferate rapidly. However, such proliferation is maintained only as long as necessary. Thereafter, regeneration activity is expected to return to its previous state.

Blood circulation to solid tumors occurs in the same way: from the arteries, through the capillaries, and into the veins. However, in the local region between exchange vessels and large venules, the direction of flow changes abruptly. Folkman describes what is happening as follows: ``When a malignant tumor releases a chemical message, endothelial cell proliferation occurs rapidly in the vicinity of the tumor.9 Capillaries emerge from the side walls of venules and extend into thin tubes. The tumor blood vessels converge at a point on the tumor from all directions.'' Because tumor blood vessels have these characteristics, many side channels (V-V side channels) connecting veins are formed, and these side channels ( shunts) are retrograde perfusion (shunts).
It is the physical element underlying the perfusion process. The significance of the ■-■ side route in tumor treatment will be explained below.

The normal kinetic pressure in the tumor vasculature is based on the change in velocity of blood flowing from the capillaries into the venous system, which is related to the cross-sectional area (V +
+ = V 2 X A 2 : where the subscript 1.2 stands for capillaries and veins, respectively). That is, these ■-V
The pressure drop in the pathway is caused by the change in flow rate as blood exits the capillary. Tumor vascular flow is thus attenuated to 2 to 15 percent of the blood flow in the surrounding tissue.

Circulation weakened in this way is identified as cancerous vasculature. The probability (property) for blood to pass through the ■-■ route is much lower than when it passes through the normal vascular system. Therefore, even if you try to add chemotherapeutic drugs to the tumor, the drugs will spread to other parts of the body.

The chance of death is much greater than if the drug were to reach the tumor.

The problem of circulating toxic elements through the system due to chemotherapy remains an obstacle to therapeutic treatment of cancer. In 1961, Tehlin et al. wrote that the leakage and circulation of chemotherapeutic agents through the system "represents one of the most important limitations to the effective perfusion of certain areas of the human body.

” I thought. Recently, in March 1981, the Journal of the American Medical Association (Journal of the A+erica)
n Medical＾5sociation) is Ka
Articles by To et al. and related articles by Chuang are included. These editorials are based on chemical embolization (chem
It describes a method that combines the injection of chemotherapeutic agents into an artery and the blocking of the blood supply to the tumor by clogging the artery. Although this method provides a long survival rate, it is limited in dosage due to systemic toxic effects. In the same way,
Fever, Wison and Lewis also
``The amount returned to the venous system remains unchanged, resulting in toxic elements not being able to travel through the body and maintain the time needed for the drug to take effect.'' Dosage is another critical factor in cancer chemotherapy. By continuing to increase the dose of the tumor treatment agent, the response rate (
There is some evidence that the response rate increases. This can be recognized in bone marrow tissue transplantation, isolated injection or local perfusion studies. Nevertheless, arterial perfusion and infusion has been shown to be superior to intravenous infusion (I infusion) in delivering drugs to solid tumors using the artery as the primary route. After that, the issue of toxicity remained unsolved.

Measures to Solve the Problems Tissue and organ toxicity and dosage are important factors in the treatment of solid tumors. However, the previous technology did not take into account the following two factors, so no results could be obtained. One is typically the V-V of the tumor vasculature.
The other is the outflow from the tumor. The key to effective perfusion is to utilize the tumor vasculature in an integrated manner and to control its outflow volume.

Retrograde perfusion according to the present invention provides a mechanism for achieving these two objectives.

To describe the present invention by way of example, in addition to two coaxially arranged catheters having a wide range of maneuverability, a pump,
Equipped with filters, analyzers, and appropriate means for regulating and monitoring the flow rate of the reservoir from the tumor. The first step is to take an arteriogram, which provides a graphical ink representation of the internal loops within the blood flow and which blood vessels preferentially enter the tumor, i.e., which extend from the tumor. Assistance in determining the largest vein is available. The perfusion process begins by retrogradely inserting two coaxial catheters through external veins into the preferred drainage of the solid tumor. One catheter is deployed at the chemotherapeutic agent entry point and forms a passageway to the V-V side channel. A second or suction catheter is provided on the distal or peripheral side, the catheter containing a therapeutic agent,
It has arterial blood flow, venous and lymphatic drainage, and the suction volume necessary to accommodate said priority drainage. Both catheters are then placed in place and a retrograde emboli is applied in critical areas of the vasculature to contain leaks. The treating physician can make necessary modifications or adjustments during treatment due to changes in cross-sectional area, reduced circulation, and other factors specific to the tumor vasculature.

A coaxial catheter placed within the preferential drainage of the tumor as described above forms, in addition to the first (m-vesicular) and second (pericellular interstitial) in-vivo spaces, a third in-vivo space. do. This is different from conventional methods. A communication port is formed within the selected organ for perfusion to an external monitoring system, thereby creating a feedback loop. The monitoring system includes pressure, concentration, temperature, time, as well as
Variables are monitored to ensure that toxicity of the system is avoided, variables that ensure proper dosages are maintained, variables that ensure that organ integrity is not compromised, etc. When a drug is delivered by an artery and passes through a solid tumor, the drug is delivered to at least one, or preferably three, of the following: the body, the tumor, and the consumed drug itself.
It changes biologically in response to all of the above. The drug is then led out of the body via the suction catheter, filtered through suitable filter means and analyzed by an analyzer. This process is repeated as many times as necessary to reach a predetermined stable state. Thus, the treatment techniques of the present invention allow clinicians to utilize retrograde perfusion as a component of the tumor vasculature. The clinician can interact the drug with the tumor and know what interactions are likely to occur. That is, it serves as a monitor for tumor growth and improves tumor homeostatic inertia (homeostatic inertia).
static 1nertia) can be interrupted, creating a feedback system that allows virtually unlimited interaction.

The present invention has three features that are commonly lacking in conventional treatment methods. First, conventional methods cannot change the basic pattern of blood flow in tumors. Second, conventional methods do not allow the cancer cells that have formed to persist and prevent the homeostatic inertia of the tumor. Finally, because traditional methods have not been able to interact with the tumor, the flow pattern cannot be controlled and, therefore, the effect of the drug, which is of critical importance in the effective treatment of cancer. Time, dosage, preferential drainage, leakage factors, and toxicity levels could not be controlled.

One advantage of this method is that the vein-to-vein shunt, i.e., V
-V side channel is provided, and the vascular flow passing through the -V side channel is no longer treated as a substrate-limiting process. The physical structure of the tumor vasculature is one limiting factor in delivering chemotherapeutic agents. Because they are located beyond the precapillary sphincter and capillary bed, the V-V tracts can be perfused exclusively randomly with this method, reducing the concentration, duration of drug action, and, in short, the biological effectiveness of chemotherapy. Gender is random. In the case of retrograde perfusion, the reduction in circulating volume through the tumor no longer needs to be taken into account. This is because the new method allows the clinician to deliver the chemotherapeutic agent through the loop created within the tumor vasculature at the pressure necessary to force flow backwards. Once the loop is created, the leak site is sealed, avoiding the flow of toxins into the system and ensuring that appropriate levels of chemotherapy reach the tumor.

The second advantage of retrograde perfusion is that it is possible to recognize the progress of the tumor, as vascular tumors with malignant characteristics grow at a constant rate. According to Folkman, tumor progression is thought to be due to the rapid increase in cell division caused by angiogenesis. When cells proliferate for a certain period of time, they first undergo dislocation (translocation).
e) invade the surrounding tissues and eventually appear as ascites cells in the abdominal cavity. According to the method of the present invention, it is possible to recognize differences in the stage of tumor progression, allowing clinicians to selectively intervene at the appropriate time and adjust the dosage, concentration, pressure, drug action time, and results to suppress hemangioma development. Treatment can be performed by appropriately combining other factors that inhibit tumor growth.

Dose response curves for chemotherapeutic agents are well known;
The higher the amount of drug, the steeper the curve. Currently, response to medication is judged by three criteria: shrinkage of tumor mass, increase in survival numbers, or biological assays. The third advantage of retrograde perfusion is that, using biological testing methods,
By accurately tracking the zero-response curve, which is the ability to evaluate the optimal conditions for steep drug-response curves, all possible measures can be taken to eliminate deviation points that represent tumor growth and decreased patient survival. I can do it.

Another advantage of the method of the present invention is that tumors can be substantially separated from the human body. Isolating the tumor from the body offers several advantages: The immune system is boosted. The passage of chemotherapeutic agents is no longer a single route, eg, only through arterial perfusion. The chemotherapeutic agent comes into constant contact within the hemangioma,
This is particularly useful when using radioactive agents. The radioactive slurry can be delivered more easily through the catheter device. The dosage of chemotherapeutic agents can be calculated according to the extent of the tumor rather than the toxic effects on tissue, organ systems. In addition, catheters with a common axis can be used as a means of hyperallimentation, that is, intravenous high-calorie infusion.
This can lead the patient to a good condition.

The most advantageous aspect of retrograde perfusion according to the present invention is that it can be used not only to deliver chemotherapeutic agents, but also for a variety of other treatments.

(Embodiment) According to the present invention, a human body can be treated using a catheter device C (FIGS. 1 and 6) that includes two balloons and have the same axis.

Catheter C is used for retrograde perfusion of the human body, in which drugs are injected into the patient's venous system in a direction opposite to the normal blood flow. The injected drug travels through the venous system to perfuse the area of the body being treated.

In an embodiment, the catheter system WC is used to inject and retrogradely perfuse a therapeutic agent, such as a chemotherapeutic agent, into a solid tumor. Variables such as concentration, duration of action of the drug, and toxicity of the system are then controlled.

Catheter device C can be used to retroperfuse active agents, such as enzymes, catalysts, or immunological agents, as described below.

During treatment according to the present invention, responses or responses from the patient are monitored using two coaxial balloon catheters (14) (16).
ial towography) scanner (10)
The double balloon coaxial catheter (14) (16) according to the present invention is observed and monitored by a video monitor (12) (Fig. 1) and a video monitor (12). The end (20) of the catheter is surrounded by an inflatable balloon (22) for sealing off the patient's vein at the site where the catheter (18) is placed. used for. The structure of the catheter (14) <16) is shown in FIG. 6, but in order to make its characteristics even clearer, it is shown in a somewhat simplified manner. An infusion catheter (18) is inserted to allow the therapeutic agent to flow through the blood vessels to the part of the body being treated. As is normally done, the end (20) of the catheter (18) has a guide wire (2
4) is provided to assist in insertion and movement to the desired location within the patient's venous system. The guidewire (24) is retrieved after the catheter (18) is in place.

The motive force to the infusion catheter (18) is
8) by a manual pump injector (26) with push and pull capacity for insertion and withdrawal. The catheter (18) contributes to forming a flow feedback loop from the tumor vessels to the outside of the body, making it possible to control the concentration, pressure, temperature, and time of the therapeutic agent introduced. In this way, system toxicity is avoided, proper dosage is maintained, and organ integrity is not compromised. The infusion catheter (18) further comprises an open passageway (25) at its end (20), which passageway forms an inlet for the therapeutic liquid delivered from the manual pump (26) to the patient's blood vessels. The infusion catheter (18) is
A second passageway or lumen (30) is provided for either injection or aspiration purposes. Inflatable balloon (2
A boat (33) is provided within the area surrounded by 2), allowing the balloon (22) to be inflated as necessary to seal off the vein and direct the flow of the chemotherapeutic agent. . A boat (31) is formed inside the catheter (18), which serves as an entrance to the rear lumen (30) of the inflatable balloon 22), and by push/pull operation of the manual pump injector (32), the vein is injected. It is possible to inject or extract liquid from the container.

A boat (34) formed in the suction catheter (35) is connected to a manual pump (3) for collecting partially or completely consumed drug after the chemotherapeutic agent has been delivered retrogradely, as described below.
6) It is designed to collect inside.

an infusion catheter (18) is disposed coaxially within an aspiration catheter (35), the aspiration catheter (35) is for transporting the collected drug to a collection manual pump (36) external to the human body; The liquid in the manual pump (36) is sent to a suitable filter and filtered.

Filtered, non-toxic chemotherapy drugs can be used as needed.
(25) and then reinjected intravenously, thereby maintaining a continuous feedback loop of flow that is essential for controlling the variables mentioned above.

The second catheter (35) of the invention also has a balloon (3
8), the balloon is inflatable within the patient's vein through the boat (40), thereby sealing the vein and preventing the flow of chemotherapeutic agents to other parts of the patient's body. Can be blocked. Boatok 42)
is formed in the catheter (35) and has a lumen or passageway (
44) Manual pump injector tank 4
6).

The manual pump injector (46) contains a filtered, non-toxic fluid that is injected into the boat (46).
2) and return to the venous system and the right side of the heart.

Catheters (18) and (35) are joined at a T-joint or side arm (47) and have a common axis.

Similarly, the liquid passages leading to the manual pumps (26) and (32) are branched, and the liquids are separated from each other by the side arm (48a).
) to prevent them from mixing. On the other hand, the liquid passages to the manual pumps (36) and (46) are branched at the side arm (481), and each liquid is separated and distinguished. Said manual pumps (26) and (36) are each provided with a tee member (49a) controlled by a lever (49b) and provided with a sample port (49c).

The process of retroperfusion according to the invention is carried out as follows. First, the tumor vasculature was determined based on conventional arteriography images.
For example, tumors within the kidney 1 (54) (52) can be detected using dyes, etc.
The tumor vasculature is marked inside as shown by reference numeral (50) (Fig. 3), and a map of the selected region is created. In this arteriography image, the tumor is marked as pale pink, and this is used as a guide for the tumor blood vessels (52) and the preferential drainage pathway (5).
6) You can know the location. By using the scanner (10), an image of the tumor vessels (52) and the preferential drainage (56) is projected onto the video screen 12). After the preliminary procedure described above, the catheter (18)
(35) is placed in the vascular system.

The coaxial catheter (18) (35) is used to access organs such as the left kidney (54) (Figure 2).
8) and enter the left renal vein (60) (Figure 3).

A video screen (1
2) The above image and guide wire (24) are used.

A guide wire (24) guides the catheter (18) through the left femoral vein (58) to the appropriate location within the left renal vein (60). At this location, preferential drainage takes place and the suction catheter (35) can collect the effluent from the tumor. Once the suction catheter (35) is in place, the guide wire (24) is connected to the suction catheter (35).
35), leaving the catheter (35) in place. Following the same process, a second or infusion catheter (18) is placed at the selected location to provide perfusion to the kidney.

Figure 4 shows the numerous tributaries (66) that flow into the great pulmonary vein (66).
4) shows the right lung (62). catheter(
18) Because it has a wide range of maneuverability, it can be repositioned as many times as necessary and to the required location within the vasculature of the lungs or other organs. Once the catheter is in place, it can be retrogradely advanced into selected blood vessels to isolate certain venous flow paths, if desired. To accomplish this process, microencapsulated drugs can be selectively introduced into tributaries of the blood vessel that are to be excluded from the perfusion process. The microencapsulated drug may be one that naturally deteriorates or one that can be recovered. The microencapsulated drug forms a third in vivo space and separates the V-V shunt beyond the tumor to be treated. In this way, placing the drug into the vein prevents the chemotherapeutic agent from leaking to other parts of the body and helps direct the flow of the drug. Balloon (22) of catheter (18) (35)
) (38) expands (Fig. 5), embolization
After the system is in place, a simulation of perfusion is performed to check for leaks or other problems in the system before performing the actual perfusion with chemotherapeutic agents. After all factors have been taken into account and necessary adjustments have been made, retrograde perfusion is initiated. This is done by forcing the chemotherapeutic agent upstream of the vein (50) by a manual pump injector (26) and via the V-V side channel into the inflated balloon of the catheter (1s) (35). (22) is pushed along the path formed by (38) and Enborai.

It should be noted that retrograde perfusion occurs over a substantial distance spanning the organ or site of the patient's body part to be treated. This is to clarify that balloon (22) and balloon (38) are placed at a certain distance from each other to ensure that the drug flows through the U1 vasculature.

The volume of chemotherapeutic agent injected into the tumor vasculature by the injector (26) and the volume aspirated by the injector (36) are maintained at equal values so that no fluid flows back into the arterial flow (Figure 5). . -numerically many parallel Vs
- V-channels are selectively formed, creating a pathway for the drug through the tumor. Since the injection volume and the suction volume are equal, there is no need for the presence of an emboli. However, emborai is useful if necessary.

A first feedback loop or passage of the therapeutic agent through the third in-vivo space is created by the chemotherapeutic agent being drawn back from the interior of the suction catheter (35) by the manual pump injector (36). be done. The chemotherapeutic agent is further filtered and then repeatedly reinjected into the tumor blood vessel via the injector (26) and the tube (25). This allows the drug to have maximum effect on the tumor and minimum effect on the human body. The feedback loop as described above is repeated as many times as necessary until the required flow balance and predetermined constancy are achieved.

The formation of a second feedback loop is achieved by forcibly injecting a drug such as a chemotherapeutic agent upstream into the vein (50) using a manual bomb injector (26).
This is done by pushing the catheter (18) (35) through the V-channel along the path formed by the inflated balloon (22) (38) towards the manual pump injector (36). Injector (3
6) The drug is transported to a boat (34) for analysis and filtration.
). The filtered fluid is then pumped by a manual pump (46) through the lumen (44) and the boat (42) to the venous system and the right portion of the heart. The second feedback loop can recirculate the filtered fluid to other parts of the body, providing stimulation to the body as an excellent means of hyperallimentation. Meanwhile, other feedback loops act on tumors.

By separating the tumor burden from the human body in this way, a third in-vivo space is created, allowing the clinician to manipulate and interact with the tumor as desired. Since the present invention can be controlled in this manner, it is possible to run two feedbank loops simultaneously and cycle back and forth indefinitely until both loops reach a predetermined stable state. In order to perform the perfusion described here, we used two feedback loop systems, which are useful not only for the treatment of solid tumors, but also as a means of hyper-allimentation to make patients healthy, and to improve the immune system. It is also applied as a means of supplying immune or activating drugs to the deficient human body.

It should also be recognized that a single catheter can be used for retrograde perfusion, depending on the situation. In these cases, the boat (25) serves as the injection point in front of the balloon (22), while the boat (31) serves as the suction or extraction boat. As mentioned above, the injection volume and extraction volume are kept equal.

The foregoing description of the invention has been described by way of example only, and various changes may be made in the size, shape, materials, and other details shown in the drawings without departing from the spirit of the invention. It is.

[Brief explanation of the drawing]

FIG. 1 is a diagram showing a situation in which a patient is receiving treatment, FIG. 2 is a diagram showing an outline of the kidney treatment method according to the present invention, FIG. 3 is an enlarged view of the kidney shown in FIG. 2, and FIG. Figure 5 shows an enlarged view of a lung undergoing treatment according to the invention; Figure 5 shows a catheter of the invention placed in the tortuous tumor vasculature;
FIG. 6 is a perspective view showing a double balloon coaxial catheter according to the present invention. (10)...CAT scanner (12)...Video monitor (14) (16)...Double balloon coaxial catheter (18)...Infusion catheter (35)
)... Suction catheter (22) (38)... Balloon (30)... Tube hole (26) (32)
(36) (46)...Manual pump injector (
31) (33) (34) (40) (42)... Boat Figure 4

Claims (1)

[Scope of Claims] [1] A method for treating a tumor in a patient's body, comprising: (a)
A catheter having a suction lumen, an injection lumen extending beyond the suction lumen, and sealing means communicating with each of the lumens is placed in the patient's vein in the vicinity of the tumor. (b) sealing the flow of fluid within the patient's veins between the injection lumen and the suction lumen with an injection sealing means; and (c) sealing the suction sealing means. (d) injecting the chemotherapeutic agent into the patient's vein through the infusion lumen; (e) collecting the chemotherapeutic agent in an aspiration lumen after the chemotherapeutic agent has passed through the tumor. [2] The method according to claim 1, which includes the step of analyzing the collected chemotherapeutic agent. [3] The method according to claim 1, which includes the step of filtering the collected chemotherapeutic agent. [4] The method according to claim 4, comprising the step of reinjecting the filtered chemotherapeutic agent into the patient's vein. [5] The method according to claim 1, comprising the step of maintaining the collection volume substantially equal to the injection volume. [6] The method of claim 1, further comprising the step of mapping the selected location of the tumor blood vessel prior to placing the catheter. [7] Claim 1, which includes the step of checking for leakage from the suction sealing means before injecting the chemotherapeutic agent.
The method described in section. [8] A catheter device for treating a tumor within a patient's body with a chemotherapeutic agent, the catheter device comprising: (a) (1) an aspiration lumen; and (2) an infusion extending beyond the aspiration lumen; (b) a sealing means for injection provided between the suction catheter and the injection catheter of the catheter means; (c) a suction seal means provided on said catheter means for sealing off flow within the patient's veins at a location past said suction catheter; and (d) a suction seal means provided on said catheter means for sealing off flow within the patient's veins at a location past said suction catheter; (e) means for injecting a chemotherapeutic agent through the infusion lumen into a vein of the patient such that the chemotherapeutic agent passes through the tumor; A catheter device for intracorporeal tumor treatment, comprising: a means for collecting . [9] The catheter device according to claim 8, comprising means for analyzing the collected chemotherapeutic agent. [10] The catheter device according to claim 8, comprising means for filtering the collected chemotherapeutic agent. [11] The catheter device according to claim 10, comprising means for reinjecting the filtered chemotherapeutic agent into a patient's vein. [12] The catheter device according to claim 8, further comprising means for maintaining the amount collected in the suction lumen substantially equal to the amount injected in the injection catheter means.