KR100983348B1 - Metal stent for ureter - Google Patents

Abstract

The present invention relates to a metal stent for ureters, unlike the other organs, the ureters can not use a metal stent in the orthodox system of the medical system, and thus there is no clinical use, the present inventors break the conventional medical common sense In the ureter, there is disclosed a metal stent for ureters fabricated to effectively overcome various factors limiting the use of the metal stent.

Ureters, stents, sheaths

Description

Metal stent for ureters {Metalic stent for ureter}

The present invention relates to a metal stent for ureters, and more particularly, to a metal stent wrapped with a fiber material woven from polytetra or fluoroethylene (PTFE) material.

The metal stent of such a structure prevents the growth of the pushed into the metal stent tube and prevents it, and adapts well to the bending of the ureter is characterized by effectively exhibiting the ureter function without the bending of the ureter or the stent is moved to the lower portion of the ureter.

Metallic stents are actively used in the clinic to prevent narrowing of blood vessels, aneurysms, narrowing of the esophagus and gastrointestinal tract, narrowing of the bile ducts, narrowing of the urethra, and narrowing of the airways, and use of an uncoated and coated stent to suit the condition of the organ and patient. Has been.

However, the urinary ureter, unlike other organs, has various obstacles, and it is accepted as a medical orthodoxy that the use of metal stents in the ureter is impossible. Although there have been studies, it is not clinically successful and is not used at all in clinical practice.

Therefore, in the case of stenosis caused by cancer tissue proliferation, metal stents are useful for narrowing of bile ducts or gastrointestinal tracts, and a single stent can be used to treat jaundice due to stenosis of the bile ducts or food intake disorder due to gastrointestinal stenosis. In most cases, the patient stays without discomfort until death.However, in the case of stenosis of the ureter due to carcinoma, a metal stent cannot be used as in the above organs, so the drainage tube should be inserted directly into the kidney through the skin to drain urine And this tube is worn until death, the quality of life is significantly reduced.

In response to this, a plastic tube called a double J tube (or double J stent) is inserted into the stenosis to temporarily open the ureter and remove the tube from the outside of the body. Occasionally, additional procedures are required because of problems such as occlusion, fracture, movement, and urolithiasis. Even when there are no complications above, the endoscope should be inserted through the urethra and changed every 2-3 months.

In addition, in the case of carcinoma of the carcinoma, the carcinoma of the carcinoma becomes more and more severe over time, so that the first one or two can be changed through the urethoscopy, but after that, it cannot be reinserted after the double J conduit is removed. There are many cases where a procedure that occurs inevitably goes out of the body and inserts a tube directly into the kidney.

Unlike other organs, when ureteral stenosis occurs, there is no proper way to alleviate the symptoms of the patient and improve the quality of life of the patient. .

Therefore, the present inventors aim to develop and provide a metal stent that can be usefully used in ureters, beyond the common medical knowledge commonly known that it cannot be used in ureters.

For factors where ureter metal stents were not available unlike other organs,

First, the stent itself is blocked by normal ureter cell overgrowth at the stent site.

Unlike other organs, the ureter is a ureter cell hyperproliferation in which normal ureter cells proliferate due to hypersensitivity to foreign substances (FIG. 1). In other organs, the growth of normal epithelial cells may occur to some extent, but it is not so big that the use of stents is weak.

Therefore, only the stenosis caused by carcinoma, which causes the stenosis of each organ, needs to be effectively expanded and maintained. However, in the case of ureters, the stent is prematurely occluded because the reaction rate of the normal cells is very severe and widespread.

In the animal experiment conducted by the present inventors, it was observed that in the case of a general stent, all of the stents were blocked by normal ureter cell hyperproliferation.

Therefore, in the ureter, as with other organs, there is a problem that effectively prevents severe overgrowth of normal ureter cells as well as stenosis by carcinoma.

Second, normal ureters that occur around both ends of the stent are blocked. Hyperproliferation of ureter cells can occur not only in the area where the stent is installed, but also in the distal and proximal ureters where the end of the stent meets normal ureteric tissues by stimulation of the stent. Occurs more severely.

Because this area is an occlusion that occurs outside the area where the stent is installed, even if there is an effective solution for the first problem (the occlusion of the stent itself), it does not solve this problem.

The cause of this problem is the overproliferation of ureter cells due to the stimulation of the end of the stent, so how to design the end of the stent to minimize the stimulation of normal ureter cells by the stent is the key to the solution.

Third, the stent is moved by the peristalsis of the ureter.

Peristalsis of the ureter is more severe than any organ of the human body, even if the stent is normally installed due to the peristaltic movement will cause the position of the stent to move badly.

In 2002, Barbalias GA et al. Reported that 13 of 16 stents failed to study because they were moved by interlocking motion.

Fourth, stimulation is caused by acute angle formation of the stent tip and normal ureter and stimulation by respiratory movement or posture change caused by the rigidity of the stent.

The ureter is a very thin diameter soft tubular tissue with no supporting structure around it.

Therefore, if the stent is not flexible, both ends of the ureter become acute with the tip of the stent, and the end of the stent pierces the normal ureter by contact to maintain the straight line of the stent. Severe stimulation leads to blockage of the ureters caused by ureter cell hyperproliferation.

If the angle is more severe, bending occurs at the site where the stent and ureter meet, causing ureter blockage by itself. In particular, the formation of this bending is mainly a problem in the upper ureter because the upper ureter close to the kidney moves with the kidney due to respiratory movements and changes in the patient's posture, so that the angle of the normal ureter is expanded and retracted. This causes friction with the tip of the stent.

therefore, The stiffness of the stent at the distal end of the ureteral stent should never be, it should be installed according to the curve of the ureter, and have a structure that moves in synchronization with the ureter movement caused by the patient's breathing or posture change.

The points described above are factors that prevent the efficient use of the metal stent in the ureter and if none of them are overcome, the metal stent cannot be effectively used in the ureter.

Korean Patent No. 10-561713 uses a superelastic shape-contributing alloy, which is a structure of the variable stent that has been used clinically for narrowing of the esophagus and gastrointestinal tract, narrowing of blood vessels and blocking of aneurysms, and bile ducts. The factors described clinically confirmed that the ureters could not be used directly.

Accordingly, the problem to be solved by the present invention is as follows.

First, to prevent occlusion of the stent itself by overproliferation of normal ureter cells in the stent site

Second, to prevent the occlusion of normal ureter around the end of stent

Third, the stent movement inhibition by peristalsis of the ureter

Finally, acute angle formation of the stent tip and normal ureter caused by the rigidity of the stent and suppression of stimulation by respiratory movement or posture change

The first problem is that the PTFE coating included in the structure of the registered patent effectively prevents the stent itself from clogging due to overproliferation of normal ureter cells.

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In addition, the third problem is that the wire structure of the stent itself, which is located at the outermost part of the patent document, is directly in contact with the ureteric epithelial cells, and thus, the epithelial cell hyperplasia serves to hold the stent wire structure, thereby suppressing the movement of the stent. It was. The above two problems could be solved by the structure of the registered patent, but the registered patent has been manufactured and used for the narrowing of the esophagus and gastrointestinal tract, narrowing of blood vessels and aneurysms, and narrowing of organs and bile ducts. It has not been studied whether human organs and other unique features can be effectively used for ureters that are not currently used in clinical practice. Therefore, the inventor inserted this structure into the test dog and demonstrated the above two effects in preparation for the effect of the uncoated stent (Cardio vascular and interventional Radiolgy, springer, New York. 2008.05.31).
However, the second task, the occlusion of normal ureters around both ends of the stent, and the fourth task, the stenosis caused by the stiffness of the stent and the ureters, and the suppression of stimulation due to breathing movement or posture change In clinical trials involving humans conducted following animal experiments, the stent described in the existing patent literature could not be overcome. This suggests that there are structural differences in the kidneys and ureters between the human body (the human body is an upright animal, so the movement of the kidneys and ureters is much greater due to the positional changes that are not seen in non-upright animals) and the stent stimulation. It is presumed that the response of the ureter is larger than that of the test dog. Therefore, in order to solve the above two problems, additional structural changes were necessary and could be overcome by the following method.

Problems and Solutions to Task 2

The structure of the stent disclosed in the patent document is completely doubled to both ends and is designed in three layers with a PTFE coating inside so that the stent end is much larger than the general stent having only one layer to expand. There is a problem that can severely stimulate normal ureter cells.

 In addition, the structure of the stent disclosed in the patent document is that the stent's wire is located at the outermost part, and the stent itself is intertwined with the ureter cells at the middle part of the stent. Although it plays a good role in preventing the movement of the stent, the direct contact with normal ureter cells at the distal end of the stent can cause much more irritation than if the soft coat is in contact with the normal ureter. It causes severe ureter cell hyperplasia, which eventually leads to occlusion of the ureter.

In order to overcome this problem, the metal stent has a two-stage stent structure as a whole, but the outer stent is removed from each end to about 1.5 cm by changing the inner stent and the outer sheath. The expansion force of only one stent, rather than the stent of the stent, was transmitted to the normal ureter, thereby reducing the stimulation of the normal ureter. Furthermore, as the coating part is located at the outermost part of the entire structure of the stent, the stent stimulates the wire. The site was not in contact with the normal ureter, but the soft film was in contact with the normal ureter, thereby minimizing irritation (Figures 2 and 5).

 Another advantage of the above structure is that the proximal occlusion of the ureter is expanded, whereas the distal obstruction often has a small diameter (2-3 mm) of the normal ureter. As a result, the six-stage stent structure of both walls completely fills the diameter of the small ureter, which significantly reduces the diameter of the ureter through which urine can flow.In addition, the olive tip used when entering the stent is filled with a stent in too small a diameter. When entering the stent is inserted before the stent to facilitate the entry and the stent is unfolded after the stent unfolds later) may not be caught.

Therefore, the stent structure of the present invention has an advantage that the urine flow can be further secured by reducing the volume by removing the outer foot stent, and the olive tip can be easily removed during the procedure.

Problems and Solutions to Task 4

The stent in the existing registered patent was fixed to the film and the two stents at both ends at this time was taken to adhere with polyurethane.

However, in this design, the wires at both ends of the bonded structure are stuck together so that they do not move freely and have rigidity.

However, the ureter is a tube-shaped organ with a very thin wall, and because there is no structure supported around it, if the end of the stent is not smooth and stiff, ureteral bending occurs between the ureter and the stent. In addition, if a severe angle between the ureter and the stent is generated, the end of the stent forms a contact in the form of stabbing the normal ureters and stimulates the ureters, causing severe ureter cell hyperplasia.

In particular, the upper ureter close to the kidney moves with the kidney due to respiratory movements and changes in the patient's posture, so that the angle spreads at the end of the stent and the ureter meets and repeats, causing friction with the end of the stent.

In order to overcome this problem, in the existing patented stents, both ends are bonded to overcome the disadvantage of causing rigidity of the structure. In the distal and proximal parts of the structure, 1.5cm away from each of the distal and proximal parts (ie, four locations where the tip of the inner and outer stents meet and the membrane meet), the suture and the stent are sealed to the end of the stent. The end of the stent did not form an acute angle with the normal ureter, and the end of the stent was able to cooperatively move according to the breathing even by the movement of the upper ureter.

In addition, the suture of the middle part was made in the form of suture of each node, and the sutures at both ends of the stent were sutured in the form of suture of each node or in the form of a single thread in the form of round weaving to give stimulation to normal ureter cells. A method of reducing the number of possible knots was adopted (FIGS. 3 and 4).

As described above, unlike the other organs, the present invention effectively overcomes various problems caused by the characteristics of the ureter alone, and thus has an excellent effect that can be usefully used for preventing or inhibiting the occlusion of the ureter.

Specific details of the present invention will be described in detail through the following experimental examples or examples.

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Animal testing:
The present inventors experimented with the following scheme using 14 metal stents in 7 dogs (mongrel dog) of 30 ~ 40kg (Table 1).

Six dogs had a non-couered stent in the right ureter, and a covered stent in the left ureter was inserted to confirm the degree of ureter occlusion due to overproliferation of ureteric epithelial cells. The degree of was compared histopathologically. Before sacrifice of the test dogs, X-ray examination was performed to confirm the movement of the first inserted stent.

Stent insertion was performed by opening the dog's abdomen, removing the lower ureter, and cutting a portion. A stent insertion device was inserted through the incision and placed in the middle ureter of the test dog under x-ray induction.

Six dogs were sacrificed at the 5th, 10th, and 15th week for pathologic findings. The seventh dog survived for 30 weeks by inserting a coated stent into both ureters.

실험결과, 본 발명의 동물실험에서 비피복 스텐트들은 전실험예에서 요관세포의 과성장에 의해 스텐트내부가 막혔으나, PTFE 피복스텐트에서는 추적기간에 관계없이 전실험예에서 스텐트의 폐색이 방지되는 효과가 있었다.

As a result, in the animal experiment of the present invention, the uncovered stents were blocked inside the stent due to overgrowth of the ureter cells in the previous experiment, but in the PTFE coated stent, the occlusion of the stent was prevented in the previous experiment regardless of the follow-up period. There was.

After sacrifice, the stenosis was measured pathologically. The stenosis rate of the ureters was 79.8% and 77.7% for the two dogs inserted with an uncoated stent at week 5, respectively, on average 78.8%. In the case of 38.55% and 35.3%, the average was only 36.9%.

At 10 weeks, the ureter stenosis rate for uncoated stents was 82.0% and 78.6%, an average of 80.3%, whereas the stenosis rate of dogs with a coated stent narrowed to 38.4% and 44.4%, an average of 41.4%. 7 and 8)

At week 15, the average stenosis of the uncovered stents was 72.0% and 76.5%, respectively, narrowing by 74.3%, and the average of 43.1%, 40.4% and 45.7%, respectively.

At 30 weeks, the test dog was inserted both sides of the coated stent and narrowed by 30.4% and 37.0%, respectively (Figs. 7 and 8).
During the follow-up period, all eight coated stents used in the experiment did not move from the initial insertion position.
Therefore, as a result of the experiment conducted by the inventors, while the stent was blocked in the uncoated stent, the coated stent effectively prevented severe ureter cell hyperplasia occurring in the ureter and prevented the stenosis and also caused the movement of the stent by the ureter's peristaltic movement. Did.

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Clinical comparison example 1; Opening experiment of the narrowed upper ureter with ureter movement

A case of a 60-year-old female patient with a ureteral stenosis caused by gastric cancer metastasis, which is a case of inserting an existing stent disclosed in the patent document. A break between the stent and the ureters occurred (FIG. 9A).

This phenomenon is particularly severe when the patient is standing, that is, when the kidneys and upper ureters are falling down, or when the patient is breathing (the kidneys are lowered down). This can happen, and the stent and ureter continue to rub against the patient's breath, causing stimulation to be delivered to normal ureter cells, leading to over-proliferation of ureter cells. However, the ureter was prematurely occluded due to stiffening of the distal end of the stent and excessive swelling and associated ureter cell proliferation, resulting in the loss of the function of the stent (FIG. 9B).

9a is a photograph taken immediately after the procedure. The ureter was severely broken at the upper end of the stent. 9b was taken 15 days after the procedure. Obstruction was observed in the upper lateral ureter of the proximal stent (see arrow). ). This is because ureter breakage and excessive stent dilatation caused severe proliferation of ureter cells.

Therefore, the existing stent failed to maintain the opening of the ureter.

On the other hand, as a successful example of the stent treatment of the present invention, an experiment in which the stent of the present invention was inserted in a 71-year-old cancer patient with upper ureter occlusion was performed. As a result of the experiment, as shown in the photograph taken immediately after the procedure (Fig. 10a), the ureter was well adapted to the normal ureter without bending of the upper ureter (Fig. 10a). The stent patency was well maintained and maintained without any symptoms. There was no evidence of hydronephrosis in the right kidney where the stent procedure was performed on jugular vein angiography performed 6 months after the procedure (Fig. 10b). Almost no cell hyperplasia and no obstructive findings maintained the patency of the ureter.

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Clinical comparison example 2; Opening test of middle and lower ureters without ureter movement

A 49-year-old female patient was diagnosed with obstruction of the central ureter due to recurrence of colorectal cancer, and we observed the normal ureter of the proximal stent of the stent on the intravenous neoplasia performed three months after the procedure. Could.

In the case of the lower ureter, the ureter cell proliferation is presumed to be the cause of ureter obstruction due to excessive stimulation of the proximal part of the stent, rather than the main cause of the stent bending. It is composed of layers of stents, and the force to expand the ureter is stronger than that of the general stent, and it was judged that the wire part of the outermost stent directly touches the ureter cells, thereby maximizing the stimulation.

The jugular vein angiography performed three months after the procedure showed that the right renal and ureters of the right kidney where the stent was inserted were significantly enlarged compared to the normal left kidney, indicating that urine did not smoothly enter the bladder through the stent. Severe narrowing of the ureters directly above the proximal part of the stent has been observed (see FIG. 11, arrows).

This site was considered to be the ureter cell hyperproliferation site caused by stimulation of the distal end of the stent and was the cause of occlusion. For reference, there was no ureter cell hyperplasia in the distal part of the stent, because the distal part of the stent was inserted into the bladder to prevent direct stimulation of the ureter cell, so that the distal end of the stent was inserted into the bladder. Because.

As a result, according to FIG. 11, jugular vein angiography findings taken three months after the procedure with the existing stent showed that the renal pelvis and ureters were significantly enlarged compared to the normal left kidney, and the ureters in the proximal part of the stent were narrowly narrowed. It is showing.

On the other hand, as an application example of the coated stent of the present invention, a 49-year-old male patient whose left kidney was developed due to metastasis of neuroendocrine cancer (Fig. 12a) was a case in which the stent of the present invention was inserted. In order to minimize the stent, each 1.5cm from the distal end of the structure of the stent removed the outer stent to ensure that only one layer of swelling force is transferred to the ureter cells, and by doing so, the wire part of the stent that causes a lot of stimulation is directly ureter cells In order to minimize the over-stimulation of the stent by allowing the soft film to contact the ureter cells without touching the bar, 9 months after the installation of the stent, the occlusion of the proximal stent did not occur in jugular vein angiography (Figure 12b). To date, 11 months after the stent operation, no secondary procedure has been performed to reopen the stent. It does not appeal to any symptoms that may be caused by.

Figure 12a shows the left middle lower ureter completely obstructed by the metastasis of neuroendocrine cell carcinoma before the procedure and the kidney is swollen due to the smooth discharge of urine, Figure 12b is a 9-month jugular vein after the stent installation of the present invention Unlike conventional stents, the renal pelvis does not swell and show the same shape as the normal kidney on the contrary, and does not complain of any symptoms that may be caused by ureteral occlusion up to 11 months after the procedure.

Whereas metal stents are used to effectively improve patients' symptoms and improve quality of life in stenosis of organs other than the ureters in the human body, many patients suffer from the lack of effective and continuous treatment or stents in the ureters. The structure of the coating stent of the present invention in the situation that is compelled to complain and discomfort can play a role like other organs in the ureter and can be effectively used in the treatment of ureter obstruction patients is a very useful invention in the medical device industry.

1 is a pathological picture showing the phenomena of ureter cells. The ureters received an external operation, causing ureter cell hyperplasia, and almost no lumen that remained inside.

2 is a cross-sectional view of the most preferred structure of the coating stent of the present invention. In the middle part, PTFE coating was inserted between two layers of stents, and 1.5cm from both ends removed the outer stent to form the inner one and the outer one.

3 and 4 are views showing the position of the stent and the method of closure.

Where the tip of the outer stent and the film meet each other, the stitches and the film of the stent are stitched together by one needle, and the ends of the entire structure, which is the site where the tip of the inner stent meets the film, are stitched separately (Fig. 3). Or take the form of reducing the number of knots by suture in the form of weaving the whole round with a single thread (Fig. 4).

5 is a real photograph showing the most preferable structure of the coating stent of the present invention.

FIG. 6 is an x-ray photograph of a non-coated stent without a covering in the right ureter and a PTFE-coated covered stent in the left ureter in an animal experiment using a dog.

7A is a macroscopic finding (a) of an uncoated stent in the right ureter of a test dog sacrificed at 10 weeks, and FIG. 7B is a pathological finding of an uncoated stent of a test dog at 15 weeks. The ureter cell hyperplasia is almost completely occluded.

8A is a macroscopic finding of the coated stent of the present invention in the left ureter of a test dog sacrificed at 10 weeks, and FIG. 8B is a pathology of the coated stent of the present invention in a 15-week sacrificed test dog. It can be confirmed grossly and pathologically that it is maintained.

Figure 9a is a photograph taken immediately after the procedure with a conventional stent rupture of the ureter at the upper end of the stent is severe, Figure 9b is a photograph of the right side of the proximal stent stenosis in the proximal upper stent on the 15th postoperative procedure.

Figure 10a is a photograph taken immediately after the procedure shows a state that is well adapted to the normal ureter without bending the upper ureter. Fig. 10B is a jugular vein renal angiogram performed 6 months after the procedure. There is no sign of hydronephrosis in the right kidney, which is performed by stent surgery, and the patency of the ureter is maintained without occlusion findings. The patient has been without symptoms because the stent has been well maintained until seven months after the procedure.

11 is a photographic view of the ureter occlusion immediately above the stent with jugular vein neoplasia findings taken three months after the operation with the existing stent.

12A is a photograph showing the complete occlusion of the mid-lower left ureter before the procedure. FIG. 12B is a normal kidney-like appearance without occlusion of the proximal stent on the jugular neoplasia after 9 months. It is a photograph showing.

Claims (6)

delete delete In the ureter coating stent that is used for opening the ureter by covering the metal stent or inserting the coating between the two metal stents, It is attached through the suture rather than adhesive to maintain the flexibility without the rigidity to the end of the metal stent, The middle portion of the metal stent is a two-layer stent and the inner coating portion of both ends of the ureter coating stent, characterized in that consisting of only the inner and outer coating to remove the outer stent. The method according to claim 3, A ureter-covered stent, characterized in that each end of the entire structure where the end of the inner stent and the film of the metal stent and the film and each of the stent nodes separately sewn or sutured and fixed in the form of round weaving with a single thread. delete delete

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