Efficacy and Safety of a Novel,Double-Layered,Coated,Self-Expandable Metallic Mesh Stent (Uventa ™ ) in Malignant Ureteral Obstructions

Abstract

Background and Purpose:

Malignant ureteral obstruction (MUO) is a common condition and an intractable situation for patients with advanced cancer. There is currently no ideal ureteral stent to release the obstruction. Our purpose was to evaluate the clinical efficacy and safety of a novel, double-layered, coated, self-expandable metallic mesh stent (Uventa^™) in MUO.

Patients and Methods:

In a retrospective design, a total of 71 ureter units (54 patients) were included from December 2009 to March 2012. Indications were those who had MUO with a polymeric Double-J stent malfunction, severe polymeric stent irritation, or severe pain during periodic stent change. Patients underwent Uventa placement using a retrograde approach.

Results:

All stents were positioned at the proper site without procedure-related complications. The overall success (no obstruction and no additional intervention except supplementary Uventa placement) and primary success (no obstruction and no additional intervention) rates were 81.7% (58/71 ureter units) and 64.8% (46/71 ureter units) during the follow-up period, which had a median of 308 (35–802) days. The most common reason for primary failure was tumor progression beyond the stent segment (75.0%), followed by reactive hyperplasia at the stent tips (12.5%), bladder invasion of the primary tumor (8.0%), and stent-related pain (8.0%). Twelve patients had overall success after secondary Uventa placement. There were no severe complications. The complications included persistent flank pain (15.5%), lower urinary tract symptoms (7.0%), acute pyelonephritis (2.8%), stent migration (2.8%), and persistent hematuria (2.8%).

Conclusions:

These data show that Uventa can be an effective and safe option for palliative treatment of patients with MUO in a large series of patients.

Introduction

M alignant ureteral obstruction (MUO) is the most common cause of intractable ureteral obstruction, and releasing the obstruction and securing kidney function is the first priority in MUO. The most promising method for urinary diversion is percutaneous nephrostomy. Many patients, however, are unwilling to undergo this procedure because of changes in body image and limitations on daily life.^1,2 Therefore, in most cases, the initial approach for managing MUO is to place a ureteral stent.³ Polymeric Double-J stents (PS) provide an acceptable patency rate in the early stage of MUO. They have some important limitations, however: The necessity of frequent exchange, irritation, and, most importantly, high incidence of catheter malfunction because of the progressive nature of primary cancer.⁴

Therefore, metallic ureteral stents have been used to overcome the shortcomings of conventional PS. Recently, the outcome of a large study of self-expanding metallic mesh stent (SEMS) was published and showed that SEMS can provide long-term decompression of MUO.⁵ Hyperplastic reaction and tumor ingrowth through the stent struts, however, still limited the efficacy of decompression. To overcome this problem, metallic mesh stents with a biocompatible cover have been used.⁶ Because of a high rate of migration, however, the externally coated, metallic mesh stent was no better clinically.⁶

Recently, a novel, double-layered, coated, SEMS (Uventa,^™ Taewoong Medical, Korea) has been used and, in the preliminary data, had good clinical outcomes with low migration rates.⁷ There are no published outcomes, however, from a large number of patients that evaluate the patency and complications of the novel stent. In this study, we evaluated the efficacy and safety of the Uventa in treating patients with MUO from our 3-year experience.

Materials and Methods

Material

We used the Uventa ureteral stent, a double-layered, coated, ureteral SEMS. The Uventa is a segmental ureteral stent comprising double-layered, shape-memory strands of nickel-titanium alloy (nitinol) that is thermally expandable and can endure extrinsic compression. It has a polytetrafluoroethylene (PTFE) cover, which is sandwiched between metallic mesh. The outer metallic mesh is designed to increase friction to reduce stent migration and provide additional radial force. The fully coated, zigzag-shaped, braided structure of the metallic mesh provides good plasticity, and the shape can be maintained even after bending (Fig. 1). The outer diameter is 7 mm, and the available lengths are 6, 8, 10, and 12 cm. Its use for ureteral obstruction was approved by the Korea Food and Drug Administration.

FIG. 1.

The Uventa^™ shape. The metal mesh and the polytetrafluoroethylene (PTFE) cover are thin. The metal mesh and PTFE are 0.127–0.152 mm and 0.03 mm thick, respectively. (a) Double-layered, combination, coated, ureteral stent. Small box shows braided Uventa structure in detail. (b) Unfixed, individual cells of the stent can overlap over a highly curved area when bent. This structure contributes significantly to the flexibility and conformability of the stent. Small box shows the curved and overlapped Uventa structure in detail.

Patients and end points

Medical records were reviewed retrospectively. For Uventa placement, we selected patients with MUO and who met one of the following criteria: Persistent obstruction even with PS; severe or intractable irritation after PS placement; or a desire to avoid the pain, fear, and inconvenience associated with regular PS exchange.

Between December 2009 and March 2012, a total of 54 patients who had advanced MUO (stage IV) underwent Uventa placement. Seventeen patients had bilateral obstruction; therefore, Uventa was inserted in a total of 71 ureter units. Before deciding to place a stent, the benefits and risks were fully discussed, and the patients agreed to the procedure. All procedures were performed in accordance with the ethical guidelines of the Declaration of Helsinki, and the study protocol was approved by the Institutional Review Board of Samsung Medical Center (IRB No. 2012-05-098-002).

Urinalysis findings, serum creatinine values, and diuretic renography and/or intravenous urography results were evaluated at baseline and every 3 months after placement (Fig. 2). To evaluate the efficacy of this novel stent, we investigated the overall and primary success rates. Overall success was defined as no obstruction on diuretic renography or intravenous urography at the last follow-up and no additional interventions, except supplementary Uventa installation. Primary success was defined as no obstruction at the last follow-up and no additional intervention, including insertion of a PS, percutaneous nephrostomy tube, or additional metallic stents. For example, if a ureter was obstructed after primary Uventa placement and it regain patency after a secondary Uventa placement until the last follow-up, this ureter was classified as an overall success but not a primary success. The primary end point was the overall success rate. To evaluate the safety of this procedure, procedure-related complications were also investigated.

FIG. 2.

Bilateral placement of multiple metallic ureteral stents (6 months after stent placement); overlapping stents are visible.

Procedures

All stents were placed by a single surgeon (DHH) under general anesthesia. Retrograde pyelography was performed to evaluate the stricture level and severity. Subsequently, a 0.038-inch rigid Amplatz guidewire (Boston Scientific, Natick, MA) was inserted through an open-end ureteral catheter (Open-End Flexi-Tip,^® Cook Medical, Bloomington, IN) to provide enough strength during stent placement. The stricture length was measured with a scaled angiographic catheter (Super Torque, Johnson & Johnson, New Brunswick, NJ). In case of severe obstruction, ureteral balloon dilation was performed using a 6-mm wide ureteral balloon catheter.

The Uventa length used was at least 4 cm longer than the total obstruction to cover enough normal ureter at both ends. The stent was loaded in the introducer system and deployed by pulling the outer sheath. It automatically expanded to impart outward radial force on the luminal surface of the ureter and gradually established patency (Fig. 3). If the stent did not achieve at least 50% of its maximal diameter, ureteral dilation was performed in the stent by using a ureteral balloon catheter. The number of stents placed depended on the stricture length. If more than two stents were placed, because of a long stricture, the stents overlapped by more than 2 cm to reinforce radial force.

FIG. 3.

Stent self-expansion to impart outward radial force on the ureter to gradually establish patency. (a) Immediately after stent deployment; (b) one day after Uventa^™ placement; and (c) 10 days after Uventa^™ placement.

When a stent was removed because of intractable pain or other causes, endoscopic procedures were used. Uventa was removed by pulling the distal tip of the stent using ureteroscopic grasping forceps. When ureteroscopic access to the stent was impossible because of a fixed, hard, and narrow ureter, antegrade stent removal was performed by using a nephroscope and nephroscopic forceps.

Results

A total of 71 ureter units were evaluated. The mean patient age was 57±12.3 years. The baseline characteristics, including location, length, and underlying cause of the obstruction are listed in Table 1. In most cases, colorectal and gynecologic cancers caused the MUO. The most common indication for metal stent placement was malfunction of a preexisting PS (69%). Two patients who had bilateral MUO and unilateral PS malfunctions had Uventa placed bilaterally (Table 2).

Table 1.

Baseline Characteristics of Ureters in Which Ureteral Metal Stents were Placed

Characteristics	Total (N=71)
Sex (case)
Male	21 (29.6%)
Female	50 (70.4%)
Side^a (case)
Right	28 (39.4%)
Left	43 (60.6% )
Site of obstruction (case)
Upper	6 (8.5%)
Mid	4 (5.6%)
Lower	14 (19.7%)
Long^b	47 (66.2%)
Stricture length (cm, mean±SD)	11.8±6.4
Previous radiation therapy (case)	39 (54.9%)
Previous diversion
Double-J stent	68 (95.8%)
Percutaneous nephrostomy	44 (62.0%)
Cause of malignant obstruction (case)
Cervix cancer	18 (25.4%)
Colon cancer	16 (22.5%)
Rectal cancer	14 (19.7%)
Stomach cancer	9 (12.7%)
Breast cancer	5 (7.0%)
Ovarian cancer	3 (4.2%)
Prostate cancer	2 (2.8%)
Miscellaneous	4 (5.6%)

17 patients had bilateral stents placed.

Stricture including more than two segments of the ureter.

SD=standard deviation.

Table 2.

Indications for Uventa ^™ Ureteral Stent Placement

Cause (case)	Total (N=71)
Double-J stent malfunction	49 (69.0%)
Fear for stent change procedure	15 (21.1%)
Severe bladder irritation by Double-J stent	5 (7.0%)
Simultaneous insertion with contralateral side	2 (2.8%)

All stent placement procedures were completed within 60 minutes, although the operative time varied, depending on the need for ballooning and the number of stents. The stent number, length, and the need for ballooning are presented in Table 3. There were no technical failures.

Table 3.

Procedure-Related Characteristics

Characteristics	Total (N=71)
Stent length (case)
6 cm	2 (2.8%)
8 cm	4 (5.6%)
10 cm	5 (7.0%)
12 cm	16 (22.5%)
Multiple^a	44 (62.0%)
Stent number (case)
1	29 (40.8%)
2	39 (54.9%)
3	3 (4.2%)
Across UVJ^b	39 (54.9%)
Ballooning
Before stent placement	7 (9.9%)
After stent placement	25 (35.0%)

≥two stents.

Ureterovesical junction.

The primary success rate was 64.8% (46/71 ureter units) during the follow-up period, which had a median of 308 days (35–802 days). The median duration from stent placement to the 25 primary failures was 98 (17–645) days. In 20 (80%) of these cases, the primary failure occurred within 6 months after the primary placement. The most common reason for primary failure was tumor progression beyond the ureteral segment covered by the primary stents (18 cases, 75.0%) (Table 4). Of 25 primary failures, 12 cases became overall successes after secondary Uventa placement. Therefore, the overall success rate was 81.7% (58/71 ureter units).

Table 4.

Outcomes of Uventa ^™ Ureteral Stent Placement

	Total (N=71)
Outcomes	Primary	Overall
Success (case)	46 (64.8%)	58 (81.7%)
Failure (case)	25 (35.2%)	13 (18.3%)
Period to primary failure (day, median)	98 (17–645)
Follow-up period (day, median)	308 (35–802)
Cause of failure (case)
Tumor progression to other segment	18 (75.0%)^a	9 (69.2%)
Mucosal hyperplasia at the stent tip	3 (12.0%)^b	0
Bladder invasion of tumor	2 (8.0%)	2 (15.4%)
Remove due to pain	2 (8.0%)	2 (15.4%)
Stent migration	0	0

10 of 18 cases became overall successes after secondary Uventa stent placement; 8 cases became overall failures (2: failed after secondary stent placement, 6: had no secondary stent placed because of poor general condition).

Two of three cases became overall successes after secondary Uventa stent placement; one case became an overall failure because the ureter was obstructed again after secondary stent placement from tumor progression.

Among 18 primary failures from tumor progression, 10 cases were overall successes. In two of these cases, the secondary stent failed again because of tumor progression. In six cases, no secondary stent was placed because of the patient's poor condition related to the advanced primary cancer. Three primary failures were because of reactive hyperplasia, two of which became overall successes. The remaining case was an overall failure because the ureter became obstructed again from tumor progression. Four primary failures were because of bladder invasion and intractable pain, and they were classified as overall failure because secondary stents were not placed. All failed cases were managed with percutaneous nephrostomy for effective diversion.

There were no severe complications during the follow-up period. In 30 cases, patients complained of pain immediately after the procedure; however, most was transient and mild. In 11 cases, the pain persisted for more than 4 weeks; however, the severity was tolerable in most patients with intermittent administration of oral painkillers. In two cases, however, stents were removed because of intractable pain (Table 5). There were two cases of upward migration. In both cases, the migration occurred after secondary stent placement. The migrations were successfully managed by pulling the migrated stent with ureteroscopic forceps to reposition it or by placing a tertiary stent. Five cases of lower urinary tract symptoms were managed with anticholinergic medication and two cases of acute pyelonephritis with temporal oral antibiotics.

Table 5.

Complications Associated with Uventa ^™ Ureteral Stent Insertion

Complication (case)	Total (N=71)
Persistent pain	11 (15.5%)
Lower urinary tract symptoms	5 (7.0%)
Acute pyelonephritis	2 (2.8%)
Stent migration	2 (2.8%)
Persistent hematuria	2 (2.8%)
Ureteral perforation	0

Discussion

Various metallic ureteral stents have been proposed to effectively manage MUO and remedy the shortcomings of conventional PS and percutaneous nephrostomy. Each stent, however, has its pros and cons, and there is no ideal stent yet.

Recently, a spiral coiled metallic stent, Resonance^® (Cook Medical), which is a double-pigtail, flexible, full-length stent, demonstrated promising results in terms of clinical effectiveness (84.6%–100%) in MUO.^8
–10 The success rate, however, was quite low (50%) in patients who had radiation therapy.^11,12 Furthermore, the Resonance has several limitations, such as necessitating periodic exchange, because it has a similar shape to the PS.^8,9,11,13 In addition, stent-related irritation has been reported in 0% to 56.5% of patients.^8,9,11,12 Additional large studies may be necessary to evaluate its efficacy in MUO and optimal patient selection.

Most metallic stents have been segmental ureteral stents. The Wallstent^™ (Boston Scientific) is a representative, self-expandable, segmental bare stent,¹⁴ and it provides more radial force than PS. In a study of the Wallstent,™ the primary patency rate was relatively low (17%–58%) because ingrowth of hyperplastic urothelium or tumor could occlude the lumen, and secondary procedures, such as coaxial ballooning and overlapping PS, were frequently needed.^15

–18 In a recent study of a large series of SEMS, 37.8% of patients (45 of 119) needed secondary interventions within 3 months after the primary procedure, and the secondary patency rate, which was similar to the overall success in our study, was 62.1%.⁵

To prevent tissue ingrowth through struts of stents, SEMS was coated by biocompatible materials.⁶ The conventional coated SEMS, however, had high migration rates (22%–81%), because adherence to the ureter lumen was lost with the covered membrane.^6,19 Therefore, coated SEMS has not been used widely.

A thermo-expandable stent has been devised to resist urothelial hyperplasia or tumor ingrowth of tumor. Memokath^™ 051 (PNN Medical, Denmark) is a spiral-shaped, nitinol and is a shape-memory stent. Recently, Memokath 051 had an 89.3% success rate (25 of 28 patients) in managing MUO from 11-year follow-up data.²⁰ Migration rates for this stent, however, were high (17.6%–27.0%). The authors recommended not dilating the ureter with a balloon during stent placement and to following up carefully to check function.^20,21

Recently, a self-expanding metal stent that can be disassembled was introduced. Allium^® (Allium LTD, Israel) is a self-expanding, elastic, nitinol stent. Allium is easy to remove because of its unique design.²² It has a biocompatible polymer cover to prevent tissue ingrowth. Limited data on this stent, however, indicate a 14.2% migration rate. More data are needed for this stent.²²

Comparing various segmental metallic stents is difficult when using published data because the nature of the primary cancer and life expectancy of patients can affect the patency rate. In addition, definitions of success vary among studies. To understand a stent's characteristics, the incidence of stent-related adverse events—including migration and encrustation—and reasons for secondary interventions should be considered together. Our current study showed an 81.7% overall success rate in MUO from a large series of patients. We consider this overall success rate to be acceptably high, considering the disease characteristics, which included aggressive and progressive malignancy. In the majority of our cases (69%), PS did not provide effective decompression, and 62% of all patients had a percutaneous nephrostomy tube before Uventa placement because of PS malfunction. The patients in this series might have had more severe ureteral obstructions than in most previous reports.^{5,9

–23}

In an animal model, the Niti-D stent structure with a PTFE cover, on which the Uventa is based, was reported to effectively prevent luminal occlusion caused by urothelial hyperplasia compared with a noncoated stent. No migration was noted.²⁴ In the current study, we found only two cases of stent migration, although it is a major concern with coated metallic stents. There were only three cases of primary failure by reactive hyperplasia at the end of the study. Furthermore, there were no obstructions from encrustation or tissue ingrowth through the stent struts.

The unique Uventa design may contribute to these good outcomes.²⁴ Its metallic, braided, sandwiched structure makes the stent resist tumor ingrowth and provides the radial force to maintain patency. The outer uncovered stent wire is expected to reduce stent migration by embedding in the ureter lumen. In addition, the cover is composed of biocompatible PTFE, which might reduce irritation and encrustation. The final unique characteristic of this stent is that it has a fully coated margin and a zigzag braided structure that might reduce marginal irritation and provide good conformability, which allow tight accommodation in the ureter and prevent stent migration.²⁴

There are fundamental limitations to treating MUO with segmental ureteral stents, because MUO tends to expand aggressively to adjacent segments of ureter, which causes recurrent obstruction. By placing additional Uventa with overlapping tips, however, we achieved a high overall success rate in newly obstructed segments.

Our data have several limitations. First, this was a retrospective study. Second, although we attributed failure to reactive hyperplasia or tumor progression, in most cases, we did not perform a biopsy of the obstructed ureter. If recurrent obstruction was combined with clinical and radiologic disease progression, we consider the cause of obstruction to be tumor progression. Third, we did not demonstrate risk factors of failure in this study. Actually, there were no preoperative factors that could predict primary and overall failure (data not shown). In addition, quality of life is important for patients who undergo palliative management; however, we did not evaluate quality of life after stent placement.

Conclusions

These data for a novel ureteral stent, Uventa, show that it can be an effective and safe option for palliative treatment of patients with MUO. The unique Uventa structure appears to prevent tumor ingrowth, provide effective radial force, and provide acceptable migration and encrustation rates. Therefore, Uventa can be a good option for patients who have intractable ureteral obstruction despite polymeric stents, have severe irritation symptoms, and do not want regular stent exchange in MUO.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

References

Kanou

, Fujiyama

, Nishimura

et al. Management of extrinsic malignant ureteral obstruction with urinary diversion. Int J Urol, 2007; 14:689–692.

Lingam

, Paterson

, Lingam

et al. Subcutaneous urinary diversion: An alternative to percutaneous nephrostomy. J Urol, 1994; 152:70–72.

Rosenberg

, Bianco

Jr , Wood

Jr , Triest

. Stent-change therapy in advanced malignancies with ureteral obstruction. J Endourol, 2005; 19:63–67.

Saltzman

. Ureteral stents. Indications, variations, and complications. Urol Clin North Am, 1988; 15:481–491.

Liatsikos

, Karnabatidis

, Katsanos

et al. Ureteral metal stents: 10-year experience with malignant ureteral obstruction treatment. J Urol, 2009; 182:2613–2617.

Barbalias

, Liatsikos

, Kalogeropoulou

et al. Externally coated ureteral metallic stents: An unfavorable clinical experience. Eur Urol, 2002; 42:276–280.

Kim

, Song

, Jo

, Park

. Palliative care of malignant ureteral obstruction with polytetrafluoroethylene membrane-covered self-expandable metallic stents: Initial experience. Korean J Urol, 2012; 53:625–631.

Liatsikos

, Kallidonis

, Kyriazis

et al.

Ureteral obstruction: is the full metallic double-pigtail stent the way to go?

Eur Urol, 2010; 57:480–486.

Benson

, Taylor

, Schwartz

. Metal ureteral stent for benign and malignant ureteral obstruction. J Urol, 2011; 185:2217–2222.

10.

Potretzke

, Chang

, Kryger

. Technique for Resonance(R) stent exchange in patients with extrinsic obstruction: Description of a novel approach and literature review. J Pediatr Urol, 2012; 8:557–559.

11.

, Li

, Huang

et al. Metallic stent in the treatment of ureteral obstruction: Experience of single institute. J Chin Med Assoc, 2011; 74:460–463.

12.

Wang

, Lee

, Luo

et al. Application of resonance metallic stents for ureteral obstruction. BJU Int, 2011; 108:428–432.

13.

Nagele

, Kuczyk

, Horstmann

et al. Initial clinical experience with full-length metal ureteral stents for obstructive ureteral stenosis. World J Urol, 2008; 26:257–262.

14.

Lugmayr

, Pauer

. Self-expanding metal stents for palliative treatment of malignant ureteral obstruction. AJR Am J Roentgenol, 1992; 159:1091–1094.

15.

Pollak

, Rosenblatt

, Egglin

et al. Treatment of ureteral obstructions with the Wallstent endoprosthesis: Preliminary results. J Vasc Interv Radiol, 1995; 6:417–425.

16.

Lugmayr

, Pauer

. Wallstents for the treatment of extrinsic malignant ureteral obstruction: Midterm results. Radiology, 1996; 198:105–108.

17.

Lang

, Irwin

, Lopez-Martinez

et al. Placement of metallic stents in ureters obstructed by carcinoma of the cervix to maintain renal function in patients undergoing long-term chemotherapy. AJR Am J Roentgenol, 1998; 171:1595–1599.

18.

Richter

, Irwin

RJ J

, Watson

, Lang

. Endourologic management of malignant ureteral strictures. J Endourol, 2000; 14:583–587.

19.

Trueba Arguinarena

, Fernandez del Busto

. Self-expanding polytetrafluoroethylene covered nitinol stents for the treatment of ureteral stenosis: Preliminary report. J Urol, 2004; 172:620–623.

20.

Agrawal

, Brown

, Bellamy

, Kulkarni

. The thermo-expandable metallic ureteric stent: An 11-year follow-up. BJU Int, 2009; 103:372–376.

21.

Klarskov

, Nordling

, Nielsen

. Experience with Memokath 051 ureteral stent. Scand J Urol Nephrol, 2005; 39:169–172.

22.

Moskovitz

, Halachmi

, Nativ

. A new self-expanding, large-caliber ureteral stent: Results of a multicenter experience. J Endourol, 2012; 26:1523–1527.

23.

Tekin

, Aytekin

, Aygun

, PeSkircioglu

, Boyvat

, Ozkardes

. Covered metallic ureteral stent in the management of malignant ureteral obstruction: Preliminary results. Urology, 2001; 58:919–923.

24.

Chung

, Lee

, Cho

et al. Comparison of a new polytetrafluoroethylene-covered metallic stent to a noncovered stent in canine ureters. Cardiovasc Intervent Radiol, 2008; 31:619–628.