Metal Stents in the Urinary Tract

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Metal Stents in the Urinary Tract Evangelos N. Liatsikos a,*, Dimitrios Karnabatidis b, George C. Kagadis c, Paraskevi F. Katsakiori a, Jens-Uwe Stolzenburg d, George C. Nikiforidis c, Petros Perimenis a, Dimitrios Siablis b a

Department of Urology, University of Patras, School of Medicine, Patras, Greece Department of Radiology, University of Patras, School of Medicine, Patras, Greece c Department of Medical Physics, University of Patras, School of Medicine, Patras, Greece d Department of Urology, University of Leipzig, Germany b

Article info

Abstract

Keywords: Metal stents Ureter Urethra

Introduction: The successful use of metal stents (MSs) in the vascular and biliary systems led several investigators to propose their use in urology. Methods: In the present study, we review the current literature and present the latest developments with the application of MSs in the urinary tract. Results: The application of MSs in the urinary tract has improved clinical outcome in the treatment of urinary tract strictures and is currently thought to be a useful tool in urology practice. Conclusions: Considerable efforts are being made to optimise stent biomaterial, the coating, and, in general, the ureteral stent design. Continuing the research interest seems to be essential for further clinical improvement, aiming to minimise stent-related morbidity. # 2006 European Association of Urology and European Board of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, University of Patras, School of Medicine, Patras, GR 265 00 Greece. Tel. +1130 2610 999386; Fax: +1130 2610 993981. E-mail address: [email protected] (E.N. Liatsikos).

1.

Introduction

The successful use of metal stents (MSs) in the vascular and biliary systems led several investigators to propose their use in urology. In 1988, Milroy implanted the first stent in the urinary tract for the treatment of urethral stricture [1]. Over recent years, their use has been expanded in the management of benign conditions, such as benign prostatic hyperplasia, urethral stricture, and detrusor sphincter dyssynergia [2,3]. Urologists initially implanted ureteral stents as a palliative intervention in

end-stage malignant disease [4–9]. Treating ureterointestinal strictures is another application that seems to be challenging. The use of MSs in this situation shows promising results but still has many untoward effects such as tissue ingrowth and recurrent obstruction [10–12]. Urothelial hyperplasia through the stent mesh, encrustation, infection, stent migration, and interaction between stent and ureteral peristalsis are important issues that influence the short-term and especially long-term results after stent insertion in a strictured ureter. Urologists have used various

1871-2592/$ – see front matter # 2006 European Association of Urology and European Board of Urology. Published by Elsevier B.V. All rights reserved.

doi:10.1016/j.eeus.2006.11.003

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experimental models to approach these issues and have proposed the use of metal mesh stents coated or covered with biocompatible materials to minimise these side-effects. Still, the ideal MS with radiopacity, low cost, long-term patency as well as resistance to encrustation, infection, and migration is yet to come. In the present study, we review the current literature and present the latest developments with the application of MSs in the urinary tract.

2.

Urethral MSs

2.1.

Types and history of urethral stents

The urethra was the first anatomic site of the urinary tract stented by Milroy et al to treat recurrent bulbar urethral stricture after optical urethrotomy [1]. Since then, permanent stents, made from

various materials or nondegradable polymers, have been applied in the urethra. Several problems such as encrustation, hyperplasia of the epithelium, and postvoiding dribbling have been reported, leading to the development of temporary urethral stents [13]. The clinical experience with the use of urethral MSs is shown in Table 1. Three types of MSs have been used to treat recurrent urethral strictures: the self-expanding mesh, the ASI titanium stent, which is a short rigid mesh of titanium wire, and the nitinol stent, which is a flexible spring in one or two parts connected by a steel wire remaining endoluminal [14]. There are some anatomic limitations of the prostatic urethra that may influence the clinical outcome after stent placement. The prostatic urethra does not always conform to the cylindrical shape of the inserted stent. In addition, the bladder neck/urethral angle is not a right angle, thus leading to difficult positioning and probably inadequate epithelial covering of the

Table 1 – Clinical experience with the use of urethral metal stents Investigators

No. of patients

Self-expanding, woven stent Milroy et al [1]

ASI titanium stent Kirby et al [2]

8

The first anatomic site stented in the urinary tract. Aim: treat urethral strictures. Follow-up period: 8 mo (6–12 mo). At mean follow-up of 8 mo, good calibre urethra. Ureteroscopy revealed complete epithelial covering of the implant at 4–6 mo.

30

Aim: treat intravesical obstruction due to benign prostatic hyperplasia. Effective micturition: 25 patients. Urinary tract infection: 10 patients, without need for stent removal. Partial epithelisation of the stent surface: in a proportion of patients.

Self-reinforced bioabsorbable stents Laaksovirta et al [41] 39

Isotalo et al [44,45]

Description

22

Covered retrievable expandable nitinol stent Song et al [25] 12

Aim: prevent postoperative urinary retention after procedures that induce prostatic edema. A lactic and glycolic acid copolymer prostatic spiral stent was used in all cases. At 4 mo, the stent was degraded into small pieces. At 6 mo, no piece of the stent was found in the prostatic urethra. In 2 patients, a stent portion was found at the bottom of the bladder. Aim: treat recurrent urethral strictures. A self-expandable, self-retaining poly-L-lactic acid double-spiral stent was used in combination with optical urethrotomy in all cases. Free voiding: all patients. Urinary infection: 2 patients. Total epithelialisation of the stent after 6 mo: all patients, except 1. Degradation at 12 mo: all patients. Stricture recurrence: 10 patients. At 46 mo: successful treatment in 8/22 patients.

Aim: treat traumatic urethral strictures near the external sphincter. Mean follow-up: 20 mo; 4/12 patients, 5/8 patients, and 2/2 patients were successfully treated with the insertion of the first, the second, and the third stent, respectively.

Temperature-based memory-shape metal stent Kamata et al [22] 1 Aim: treat ischuria after repaired cloacal anomaly with a temporary stent. A nickel-titanium alloy stent was implanted in a 2-yr-old girl. Asymptomatic stent migration into the bladder was observed in 2 mo. VanDijk et al [21] 108 Aim: treat severe lower urinary tract symptoms due to benign prostatic enlargement. The bell-shaped nitinol prostatic stent was inserted in all cases. Successful insertion: 97%. Spontaneous voiding: all patients. Main complications: haematuria, urge incontinence, and migration. This stent does not seem suitable for clinical use. VanDijk et al [20] 35 Aim: treat lower urinary tract symptoms due to bladder outlet obstruction. An hourglass-shaped nitinol prostatic stent was used in all cases. Failure of insertion: 5 patients. Spontaneous voiding: all patients. Main reason for stent removal: stent migration (93%), in most cases towards the bladder. Uneventful removal: in all, except for 1.

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stent [15]. However, the advantage of stent placement over the conventional urethral catheter, to overcome the urethral stricture, has already been reported with regard to the risk for urinary tract infection [16]. The removal of the urethral stent is still an issue of concern. The permanent stents remain on the urethral wall and keep the lumen permanently open, leading to uncontrolled dribbling after voiding [1]. Besides, they induce mucosal hyperplasia through the stent openings, with the potential risk of stent obstruction. If stent obstruction occurs, repeat endoscopic resection, stent replacement, or even surgical removal may be needed. To resolve these problems, several types of temporarily placed or bioabsorbable urethral stents were introduced [17,18]. Currently, urologists tend to temporarily stent the urethra with the use of bioabsorbable or thermoexpandable memory shape stents. The first ones are biodegraded, leading to self-remotion. The second ones are relatively easily removed due to their nature. They soften at a specific temperature and regain their shape in a different one. The first bioabsorbable urethral stent was introduced in an experimental animal study by Kemppainen et al in 1993 [18]. Bioabsorbable materials used in urology are polyactic acid, polyglycolic acid, and copolymers of lactide and glycoside. The biodegradation time depends on the stent material and processing methods and ranges from 2 to 12 mo. Isotalo et al compared a new braided self-reinforced poly-L-lactic acid (SR-PLLA) urethral stent with the spiral biodegradable SR-PLLA stent and a stainless steel stent in rabbits [19]. The results of this experimental study were encouraging because the degradation of the new stent seemed more controlled and more favourable compared to the disintegration of the previous stent forms. But clinical studies are needed to prove the efficacy of this new stent in the strictured urethra in humans. Several thermoexpandable shape-memory stents have been used in urethral strictures. Van Dijk et al used a hourglass-shaped nitinol prostatic stent in the management of bladder outlet obstruction. Improvement of the symptoms was observed, but the application of this stent was limited due to high migration rate and, consequently, the need for its removal [20]. The same authors also introduced the use of bell-shaped nitinol stent (Endocare) with promising results [21]. Memokath 028 (Engineers & Doctors A/S, Hombaek, Denmark) was placed by Kamata et al for 6 mo in a 2-yr-old girl with ischuria after repaired cloacal anomaly. Their observations show that the temporary application of this memory metal stent in paediatric patients with functional

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obstruction can be a safe and effective alternative [22]. The ideal urethral stent is still under development. Its predominance over the urethral catheter in the treatment of urethral strictures has already been described, but the complications that may occur after stent placement in the urethra minimise its use and prompts a more appropriate urethral stent design. 2.2.

The stent influence on the urethra

The interaction between the stent material and the endothelium of the urethra is a significant issue that influences the long-term outcome and the patient’s quality of life after stent placement. Stent obstruction or migration, encrustation, injury of urethra, and formation of granulation tissue are some of these issues. Experimental studies are being conducted to evaluate the possible effects of the stent insertion to the urethra and develop a more appropriate urethral stent (Table 2). MSs can easily migrate and cause local pain, discomfort, and hyperplasia of the mucosa. Encrustation has been described while using permanent urethral stents [2]. When the MS is fully incorporated into the periurethral tissues, it is difficult to be removed and even surgical procedures may be needed. For this reason, bioabsorbable or temperature-based shape-memory stents are being investigated [18–22]. However, with use of these kinds of stents, migration is more possible. In addition, the sudden breakdown of the bioabsorbable stent may cause urethral obstruction from the broken pieces. Currently, there is a continuous search for the development of bioabsorbable urethral stents with a reduced possibility for migration and urethral obstruction. Restenosis or blockage of the stent may occur due to either tissue hyperplasia or to formation of granulation tissue. Tissue hyperplasia at either end of a covered stent is usual, leading to difficult stent removal. For this reason, reduction or prevention of the development of tissue hyperplasia is necessary [23]. Granulation tissue formation usually resolves after stent removal [24]. To evaluate the possible interactions between stent and urethral endothelium, Ko et al conducted an experimental study in normal canine urethras [24]. They used a polyurethane-covered retrievable nitinol stent. Migration of the stent (partial or complete) was reported and therefore confined its use. Granulation tissue was observed at both ends of the stent in 17 of 20 dogs. The potential migration and the disruption of the polyurethane membrane

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Table 2 – Experimental studies in urethral stenting Investigators

Issue

Description

Ko et al [24]

Evaluate the use of a retrieval stent and estimate if granulation tissue resolves after stent removal in a canine urethra

Kemppainen et al [18]

Examine the suitability of biodegradable polymers for a urethral stent in rabbits after urethrotomy

Isotalo et al [19]

Compare a biodegradable SR-PLLA urethral stent to the former spiral biodegradable SR-PLLA stent and stainless steel stent in the rabbit urethra. Evaluate a paclitaxel-eluting covered stent in a canine urethral model. Evaluate the biocompatibility of a caprolactone, copolymer-coated, SR-PLLA urethral stent by a rabbit muscle implantation test.

Shin et al [23] Isotalo et al [17]

Isotalo et al [46]

Evaluate the biocompatibility of a bioabsorbable x-ray–positive SR-PLA 96/4 urethral stent by a rabbit muscle implantation test.

were also some of its limitations. Because of these interactions, the authors concluded that this stent may be suitable for urethral use only after making technical modifications. Finally, the influence of the stent on the external sphincter when applied to treat nearby strictures is an important issue because it can lead to incontinence after stenting. Song et al proposed the use of a covered, retrievable, expandable nitinol stent to preserve continence after stent placement [25].

3.

Ureteral MSs

3.1.

Types and history of ureteral stents

The aim of ureteral stent implantation is to ensure the unobstructed drainage of urine from the renal pelvis to the bladder. The ideal stent should be inert, resistant to encrustation, and suitable for long-term use; in addition, its implantation in the organ should not cause any pain. The basic characteristics that ureteral stents should have to ensure safe and longterm effective urine drainage are summarised in Table 3. There are four general types of MSs for ureteral use: the self-expandable, the balloon-expandable, the covered, and the thermoexpandable shapememory stents. The most commonly used MSs in the ureter are the self-expanding stents although urologists’ interest has recently reoriented to covered stents, in an effort to minimise tissue ingrowth,

Technically successful stent placement: all dogs. Granulation tissue at both ends of stent: 17/20 dogs. Stent removal failure: 2 cases. Diminished granulation tissue: 2 wk after stent removal. A biodegradable self-reinforced poly-L-lactic acid (SR-PLLA) was implanted in 16 male rabbits. Within 6 mo, minimal tissue reaction around the stent material. This stent seems a promising material for a urethral stent with regard to prevention of restenosis. Metal stents caused the strongest inflammatory reaction and induced epithelial hyperplasia and polyposis earlier than the biodegradable stents. Local delivery of paclitaxel from covered stents reduced tissue hyperplasia after stent placement. Acute tissue reactions attributable to operative trauma in all specimens at 1 wk. After 6 mo, chronic inflammatory changes and foreign-body reactions only in positive controls (rods made of latex). The stent worked well, with good biocompatibility and less encrustation than in metal stents. After 6 mo, chronic inflammatory changes and foreign body reaction only in positive controls (rods made from latex).

which eventually threatens to compromise ureteral patency. The ability of covered stents to reduce tissue ingrowth initially appeared promising but failed to prove efficacy when used in the ureter due to a high rate of migration [26]. The overall experience with the use of ureteral MSs is shown in Table 4. The Wallstent (Microvasive, Natick, MA) is a selfexpandable endoprosthesis and is composed of braided biomedical cobalt-based alloy monofilaments. It is available in a diameter of 7 or 10 mm and in a length of 4, 6, and 8 cm [12]. Memokath 051 (Engineers & Doctors A/S) is a thermoexpandable shape-memory stent, composed of a nickel and titanium alloy [27]. It has a unique

Table 3 – Basic properties of the ideal ureteral stent [47] Property Memory Durometer Elasticity Tensile strength Elongation capacity Biodurability Biocompatibility Coefficient of friction Radiopacity

Description Maintenance of its position within the ureter Strength of memory Manipulation of its shape Crystallisation and cross-linking in the biomaterials Elongation at stent breakage Ability to exist within the body without degradation of its structure and function No significant effect of the stent to the urothelium Facility of its passage or exchange Facility of stent visualisation during fluoroscopy

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Table 4 – Types of metal stent (MS) and experience Type of MS

No. of patients/ strictures

Self-expanding and balloon-expandable MS Lugmayr and Pauer [8] 23/30

Pauer and Lugmayr [9]

Pollak et al [48]

12/15

8/11

Lugmayr and Pauer [5]

40/44

Barbalias et al [4]

12/14

Barbalias et al [10]

14/14

Rapp et al [12]

Covered MS Barbalias et al [26]

Trueba Arguinarena et al [29]

Thermoexpandable shape-memory MS Kulkarni and Bellamy [27]

4/6

16/20

20/29

15/22

Kulkarni and Bellamy [28]

28/37

Klarskov et al [49]

33/37

Description

Follow-up period: 31 wk (3–75 wk), type of obstruction: malignant. Self-expanding MS were used in all strictures. Primary patency was 83% after 30 wk. Macrohaematuria was observed in 1 patient and incrustation in 2 patients. Follow-up period: 3–31 wk, type of obstruction: malignant. Self-expanding MSs were used in all strictures. Haemorrhagia was reported in 1 patient, incrustation in 2 patients, and obstruction distal to the stent in 3 patients. Type of obstruction: malignant and benign. Two of 5 malignant strictures was occluded within 1 mo and 1/6 benign strictures remained patent in 11 mo. Follow-up period: 10.5 mo (1–44 mo), type of obstruction: malignant. Self-expanding MSs were used in all strictures. 49% needed reintervention and 3 ureters finally had to be abandoned. Follow-up period: 9 mo (8–16 mo), type of obstruction: malignant. In 6 patients, we used self-expanding and in the other 6, balloon-expandable MSs. Second intervention was necessary in 3 cases due to urothelial hyperplasia, tumour ingrowth, and local recurrence of primary cancer invading the upper end of the stent. Follow-up period: 15 mo (9–24 mo), type of obstruction: malignant. Self-expanding MSs were used in all strictures. Only 2 patients needed further intervention. Follow-up period: 10 mo (7–12 mo), type of obstruction: malignant. Self-expanding MSs were used in all strictures. No recurrence was observed.

Follow-up period: 8 mos (6–16 mo), type of obstruction: malignant. Thirteen of 16 patients needed second intervention due to stent migration. At the end of the follow-up period, patency was 100%. Follow-up period: 3 mo for 3 patients, 6 mo for 4 patients, 12 mo for 4 patients, 24 mo for 7 patients; type of obstruction: malignant and benign. In 3 patients, insertion of second stent was needed because of migration of the first stent. At the end of the follow-up period, patency was 100%.

Follow-up period: 10.6 mo (2–21 mo), type of obstruction: malignant and benign. In 3/15 stent migration occurred and a shorter Memokath 051 (Engineers & Doctors A/S) was inserted because of bladder irritation. At the end of the follow-up period, patency was 100%. Follow-up period: 19.3 mo (3–35 mo), type of obstruction: malignant and benign. Nine stents in 7 patients were removed, 4 of them requiring no more intervention, 1 led to nephrectomy, 1 to renal failure, and 1 to cystectomy with nephroureterectomy. Follow-up period: 14 mo (3–30 mo), type of obstruction: malignant and benign. A total of 22 nonfunctioning stents in approximately 5 mo: 10 of them migrated and 12 malfunctioning. Four stents were occluded by stone after 1–10 mo.

tight spiral structure that prevents endothelial growth. This endoprosthesis softens below 10 8C and regains its shape when reheated to 50 8C. Because of its thermal shape memory, it is easily removable if indicated. Kulkarni and Bellamy used this MS in managing both benign and malignant ureteral obstruction and showed that this stent has very good long-term results in the management of malignant stricture or recurrent benign strictures. In addition, no stent migration or infection was reported [27,28]. Trueba Arguinarena and Fernandez del Busto used a self-expanding polytetrafluoroethylene-covered nitinol stent (Hemobahn Endoprosthesis, W. L. Gore and Associates, Flagstaff, AZ) to treat both benign and malignant ureteral stenosis [29]. This stent proved to be safe and effective in managing ureteral stenosis

and showed high resistance to calcification. Hyperplasia was observed only at the stent ends and only in a few cases and it did not cause obstruction. Migration of the stent occurred in 3 of 20 patients. Long-term follow-up is needed to prove that this covered nitinol stent inhibits ureteral hyperplasia. Recently, Borin et al published data on a woman with intractable ureteral obstruction due to retroperitoneal fibrosis after metastatic breast cancer. They used a newly developed all-metal double-pigtail Resonance stent (Cook Ireland, Limerick, Ireland), which is constructed of MP35N alloy, a composite of nonmagnetic nickel-cobalt-chromium-molybdenum. The obstruction had previously resisted the insertion of two 6F double-pigtail stents. The ureter was found to be patent in the renal scan at a 4-mo follow-up [30].

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Fig. 1 – Balloon dilation of the stenotic ureteral segment.

The insertion technique (antegrade or retrograde) has been previously described in detail [4,31]. Briefly, a standard percutaneous nephrostomy, followed by nephropyeloureterography, is done to exactly define the obstructed segment. The stenosed segment is then passed with the use of a 0.018-, 0.035-, or 0.038inch guidewire. Dilatation is performed with the use of a high-pressure balloon catheter (8–10 mm diameter; Fig. 1). The space for stent passage is then adequate and the endoprosthesis is inserted over the guidewire. It is placed in such a position that the upper end bypasses the stricture by at least 3–4 cm while the lower end extends intravesically for 0.5–1 cm from the ureteral orifice. Two or more MSs can be placed in sequence if necessary, overlapping by at least 2–3 cm to bridge longer obstructed ureteral segments. If the MS does not expand to the desired diameter, supplementary balloon dilatations may be performed. After the stent placement is completed, a plain radiograph of kidneys-ureters-bladder, ultrasonography, and antegrade nephrotomography are obtained to confirm ureteral patency. The nephrostomy tube can then be removed. Urinalysis, urine culture, serum creatinine measurement, transabdominal ultrasonography, and excretory urography are performed in scheduled order (Fig. 2). Renography with diethylenetriamine pentaacetic acid (DTPA) can be performed if indicated and ureteroscopy may be necessary to assess and treat eventual encrustations. Virtual endoscopy (VE) has also been proposed as a noninvasive method to evaluate patency of the stented ureter [32–34] (Fig. 3).

Fig. 2 – Excretory urography: patent stented ureteral segment.

Since the first stent implantation in the ureter, considerable efforts have been made to improve stent design, aiming to facilitate insertion, prevent migration, and permit maximum flow of urine into the bladder. Nevertheless, the ideal stent does not exist. 3.2.

The stent influence on the ureter

Urothelial hyperplasia of the stent lumen has been the principal problem after the insertion of a metal prothesis in the ureter (Fig. 4). It is a common phenomenon that may influence patency of the stented ureter and has been verified endoscopically. Thijssen et al have shown that the grade of urothelial hyperplasia seems to depend on the degree of the force exerted on the ureteral wall as well as on the extent of the ureteral overstretching and the resulting urothelial trauma [35]. Desgrandchamps et al conducted an experimental study in pigs, inserting eight stents. Only one of them was observed to be patent 35 d after the insertion [36]. Careful insertion of the stent with avoidance of overextending the strictured area of the ureter is needed. Urothelial hyperplasia usually regresses 4–6 wk after the insertion of the stent, avoiding the narrowing of the ureteral lumen [4,5,8–10]. Flueckiger et al reported that during the first 2 wk after the stent insertion reactive swelling of the urothelium, but not hyperplasia, occurs, leading to constriction of the ureteral lumen [7].

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Fig. 4 – Excretory urography: urothelial hyperplasia jeopardising luminal patency.

to the presence of the coating material, and, finally, the enhanced ureteral peristalsis are considered strong arguments against the use of coated stents for the management of ureteral strictures. In our previous publications, we described a trumpet-like configuration of the ureter adjacent to the upper extremity of the MS, which did not hinder ureteral patency [10,26] (Fig. 5). The autopsy findings in a patient with malignant ureteral stricture, who died 2 mo after MS implantation, revealed a fibrotic reaction in the lumen of the balloon expandable Fig. 3 – Virtual endoscopy. (a) Patent stented ureteral lumen and (b) stenotic distal part of the endoprosthesis.

The concept of a covered MS was introduced to overcome the problem of hyperplasia growth. Nevertheless, migration of a coated MS may occur, with a frequency of 81.2% observed in one of our previous publications [26]. Migration may be corrected by coaxial insertion of another prothesis. In a previous study, we implanted coated MSs in 16 patients with malignant ureteral stricture. Thirteen of the 16 showed migration of the endoprosthesis, which caused ureteral obstruction and subsequently ipsilateral lumbar pain. The floating stents were removed cystoscopically from the bladder and bare MSs were then implanted, achieving ureteral patency for a mean follow-up of 8 mo [26]. The high and fast migration rate of the coated stents into the bladder, the confirmed ‘‘non-anchorage’’ of the coated stents into the ureteral wall due

Fig. 5 – Computed tomography/three-dimensional reconstruction: trumpet-like configuration adjacent to the proximal end of the metal stent.

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stent, probably due to an overextension of the ureteral wall causing urothelial trauma [4]. The effect of the MS on ureteral dynamics is an issue of controversy. The presence of foreign material in a peristaltic organ increases the peristalsis of the organ aiming to ascertain lumen patency. Hemikoglu et al suggested that the aperistaltic segment of the stented ureter in conjunction with urothelial peristalsis causes urinary stasis and thus encrustation of the uncovered areas of the MS [37]. Encrustation of the MS is a significant factor that may limit the long-term use of the ureteral endoprosthesis. Both the biomaterial and the patient’s history influence the risk of encrustation. Tunney et al compared the resistance of different stent biomaterials to encrustation and concluded that a stent resistant to encrustation should be formed from a biomaterial resistant to bacterial infection and subsequent biofilm formation [38]. Pauer and Lugmayr reported the presence of encrustations in a small area of Wallstents that was not covered by endothelium because it did not embrace the ureteral wall [9]. Experimental studies are being conducted to investigate the microscopic urothelial changes that occur after stent implantation as well as to develop a covered or coated endoprosthesis that will minimise complications (Table 5). Greater understanding of

the interaction between the stent material and urine, with improvements in biomedical engineering, may reduce some of the undesirable events associated with ureteral stenting.

4.

Our experience

Our experience with MSs dates back to 1997 when we applied self- and balloon-expandable MSs in the management of malignant disease in 12 patients. A secondary intervention was necessary in three of them due to urothelial hyperplasia, tumour ingrowth, or recurrence of primary tumour in the upper end of stent [4]. Consequently, we applied MSs in the treatment of benign anastomotic strictures developed after ureteroileal diversion and afterwards in ureteropelvic junction obstruction with encouraging results [10,33]. MSs covered with various biocompatible materials have already been used with success in the vascular arena and with better clinical outcome compared to bare MSs. The aim was to limit the ingrowth of intimal hyperplasia along the length of the treated arterial segment and thereby to improve patency as compared to conventional angioplasty and stenting. This observation in the vascular system has led urologists to experimentally use this kind of stent in the urinary tract. Their main

Table 5 – Experimental studies in ureteral stenting Investigators Wrigth et al [50] Desgrandchamps et al [36]

Issue Placement of self- and balloon-expandable metal stents (MSs) in normal/stenotic canine ureters Placement of self-expanding MS in pig ureters

Liatsikos et al [39]

Placement of bare MS and internally or externally coated MS in normal pig ureters

Thijssen et al [35]

Placement of self-expanding MS in histologically normal canine ureters

Antimisiaris et al [51]

Simulation of in vivo conditions after the placement of a liposome-covered MS, which slowly releases dexamethasone Bare MS and MS lined with porous biocompatible polymer in canine ureters

Leveillee et al [52]

Liatsikos et al [40]

Placement of bare MS and paclitaxel drug-eluting stent (DES) in normal pig ureters

Description Complete occlusion in all stented ureters due to mucosal hyperplasia in 4–8 wk. Distal narrowing was observed, due to functional discrepancy between adynamic stented ureter and normal underlying ureter. Urothelial hyperplasia was another feature, but it did not play an important role in obstructing porcine ureters. Coated stents cause minimal tissue ingrowth but tend to migrate towards bladder, whereas bare MSs cause less inflammation of surrounding tissues. Ureters remained patent. MS was not incorporated within the ureter wall. Penetration of epithelium/submucosa between wire struts and areas of fibrosis in submucosal layer were observed. May be an efficient method of treating ureteral stent obstruction. MSs lined with a biocompatible material help prevent tissue ingrowth, whereas bare MSs cause ureteral obstruction and hydronephrosis. Paclitaxel-DES generated less inflammation and less hyperplasia of surrounding tissues, thus maintaining ureteral patency.

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placed covered MSs in 16 patients with malignant ureteral obstruction but unfavourable clinical results were observed. No local or systemic infection was described, but a high and fast migration rate of the MS into the bladder occurred due to ‘‘nonanchorage’’ of the implanted stent into the ureteral wall. This finding was considered to be a strong argument against their use in the ureter [26]. Recently, we published our experience with the use of a drug-eluting stent (DES) in an experimental pig model. The results seem promising. DESs are used in the treatment of strictures of coronary vessels, aiming to minimise the risk of restenosis. It has been shown that they reduce inflammation and smooth muscle proliferation. We thus postulated that they may have similar tissue effects in the urinary tract and reduce potential luminal occlusion in the stented ureter. Less inflammation and less hyperplasia of surrounding tissues were observed with DESs compared to bare MSs, thereby maintaining ureteral patency (Fig. 6). Still, long-term animal and human trials are needed to further validate these promising initial results [40].

5. Fig. 6 – Section of the pig stented ureteral lumen. The fine epithelial lining is evident covering the metal mesh (a). The patency of the ureteral lumen is documented ureteroscopically (b).

disadvantage is the high rate of migration, the intense inflammatory reaction of the urothelium due to the presence of the lining material, and, finally, the easier infection of this kind of stent compared to the indigenous grafts. The more intensive inflammatory reaction generates fibrous tissue that is compressed beneath the prosthesis. Still, clinical experience is limited and further experimental as well as clinical investigation is deemed necessary for their evaluation in the urinary tract. To find a more appropriate MS and improve our results, we conducted an experimental study in pigs, using internally and externally coated MSs, and compared the results between coated and bare MSs. The follow-up led to controversial outcomes. The bare MSs generated less inflammation of the surrounding tissues but coated stents had the advantage of minimal tissue ingrowth. Additionally, coated stents tended to migrate into the bladder, jeopardising ureteral patency [39]. Consequently, we

New perspectives

Since the first stent implantation in the field of urology, efforts have been made to improve stent design but still the ideal MS has not been developed. The use of coated or covered MSs as well as bioabsorbable stents seems promising in minimising stent-related morbidity and improving longterm urine drainage into the bladder [23,40–43]. Pharmacologically active agents can be incorporated onto covered or coated MSs. The agent may be placed either directly to the polymeric surface of the stent (coated MS) or into the core of the stent’s polymeric structure (DES). In the first case, the agent is pharmacologically active at the surface and can prevent infection or encrustation, whereas in the second case, the pharmacologic agent is delivered locally in a sustained-release fashion and may have potential activity at the urothelium. Experimental studies with the application of DESs have already been initiated in both the urethra and the ureter. DESs tend to reduce neointimal hyperplasia by inhibiting vascular smooth muscle cell proliferation and migration. We used a paclitaxeleluting covered stent in the pig ureter model with promising results [40]. Shin et al applied a similar stent in a canine urethral model and described less tissue hyperplasia reaction compared to polyurethane-covered stents [23]. DESs are being used in the treatment of strictures in coronary vessels to

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minimise the risk of restenosis because they reduce inflammation and smooth muscle proliferation. We tend to believe that the application of DESs will solve many of the problems of stenting in the urinary tract, but more long-term animal and human trials are needed to prove their efficacy in this field. However, a retrievable stent design is needed in DESs to make the removal easier [23]. Bioabsorbable stents are still being developed. Little is known about their behaviour in the urinary tract but the first results seem promising. Isotalo et al evaluated the use of a bioabsorbable SR-PLLA urethral stent combined with optical urethrotomy in the treatment of recurrent urethral stricture in 22 patients [44]. Thirteen recurrent strictures were reported within 15 mo. At 6 mo, the stent was totally epithelialised in almost all patients and at 12 mo, the stents were totally degraded in all patients. Their long-term results showed that in most of the patients with stricture recurrence at the stent site, the recurrence was discovered during the weakening of the stent [45]. The stent seems to collapse, leading to permanent urethral obstruction, if sudden heavy compression happens during the early degradation period. The biocompatibility of the bioabsorbable stents has been reported to be good [17,18,46].

6.

Conclusions

The application of MSs in the urinary tract has improved clinical outcome in the treatment of urinary tract strictures and is currently thought to be a useful tool in urology practice. Considerable efforts are being made to optimise stent biomaterial, the coating, and, in general, the ureteral stent design. Continuing the research interest seems to be essential for further clinical improvement, aiming to minimise stent-related morbidity. References [1] Milroy EJ, Chapple CR, Cooper JE, et al. A new treatment for urethral strictures. Lancet 1988;1:1424–7. [2] Kirby RS, Heard SR, Miller P, et al. Use of the ASI titanium stent in the management of bladder outflow obstruction due to benign prostatic hyperplasia. J Urol 1992;148:1195–7. [3] MacMillan RD, El Harram M. Urethral stents as an alternative to sphincterotomy in high pressure bladders. Read at annual meeting of International Continence Society, Halifax, Nova Scotia, Canada, September 1992, p. 111 (abstract). [4] Barbalias GA, Siablis D, Liatsikos EN, et al. Metal stents: a new treatment of malignant ureteral obstruction. J Urol 1997;158:54–8.

[5] Lugmayr HF, Pauer W. Wallstents for the treatment of extrinsic malignant ureteral obstruction: midterm results. Radiology 1996;198:105–8. [6] VanSonnenberg E, D’Agostino HB, O’Laoide R, et al. Malignant ureteral obstruction: treatment with metal stents— technique, results, and observations with percutaneous intraluminal US. Radiology 1994;191:765–8. [7] Flueckiger F, Lammer J, Klein GE, et al. Malignant ureteral obstruction: preliminary results of treatment with metallic self-expandable stents. Radiology 1993;186:169–73. [8] Lugmayr H, Pauer W. Self-expanding metal stents for palliative treatment of malignant ureteral obstruction. AJR Am J Radiol 1992;159:1091–4. [9] Pauer W, Lugmayr H. Metallic Wallstents: a new therapy for extrinsic ureteral obstruction. J Urol 1992;148:281–4. [10] Barbalias GA, Liatsikos EN, Kalogeropoulou C, Karnabatidis D, Siablis D. Metallic stents in gynecologic cancer: an approach to treat extrinsic ureteral obstruction. Eur Urol 2000;38:35–40. [11] Kurzer E, Leveillee RJ. Endoscopic management of ureterointestinal strictures after radical cystectomy. J Endourol 2005;19:677–82. [12] Rapp DE, Laven BA, Steinberg GD, Gerber GS. Percutaneous placement of permanent metal stents for treatment of ureteroenteric anastomotic strictures. J Endourol 2004;18:677–81. [13] Badlani GH. Role of permanent stents. J Endourol 1997;11:473–5. [14] Yachia D. The use of urethral stents for the treatment of urethral strictures. Ann Urol (Paris) 1993;27:245–52. [15] Milroy EJ, Rickards D. Anatomic limitations of prostatic urethra in using cylindrical stents. J Endourol 1997;11:455– 8. [16] Egilmez T, Aridogan IA, Yachia D, Hassin D. Comparison of nitinol urethral stent infections with indwelling catheter-associated urinary-tract infections. J Endourol 2006;20:272–7. [17] Isotalo T, Halasz A, Talja A, Tammela TL, Paasimaa S, Tormala P. Tissue biocompatibility of a new caprolactone coated self-reinforced self-expandable poly-L-lactic acid (SR-PLLA) bioabsorbable urethral stent. J Endourol 1999;13:525–30. [18] Kemppainen E, Talja M, Riihela¨ M, Pohjonen T, Tormala P, Alfthan O. A bioresorbable urethral stent. An experimental study. Urol Res 1993;21:235–8. [19] Isotalo TM, Nuutine J-P, Vaajanen A, et al. Biocompatibility properties of a new braided biodegradable urethral stent: a comparison with a biodegradable spiral and a braided metallic stent in the rabbit urethra. BJU Int 2006;97:856–9. [20] Van Dijk MM, Mochtar CA, Wijkstra H, Laguna P, de la Rosette JJMCH. Hourglass-shaped nitinol prostatic stent in treatment of patients with lower urinary tract symptoms due to bladder outlet obstruction. Urology 2005;66:845–9. [21] van Dijk MM, Mochtar CA, Wijkstra H, Laguna MP, de la Rosette JJMCH. The bell-shaped nitinol prostatic stent in the treatment of lower urinary tract symptoms: experience in 108 patients. Eur Urol 2006;49:353–9.

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[22] Kamata S, Usui N, Kamiyama M, Yoneda A, Tazuke Y, Ooue T. Application of memory metallic stents to urinary tract disorders in pediatric patients. J Pediatr Surg 2005;40:E43–5. [23] Shin JH, Song HY, Choi CG, et al. Tissue hyperplasia: influence of a paclitaxel-eluting covered stent—preliminary study in a canine urethral model. Radiology 2005;234: 438–44. [24] Ko G-Y, Kim G-C, Seo T-S, et al. Covered, retrievable, expandable urethral nitinol stent: feasibility study in dogs. Radiology 2002;223:83–90. [25] Song HY, Park H, Suh TS, et al. Recurrent traumatic urethral strictures near the external sphincter: treatment with a covered, retrievable, expandable nitinol stentinitial results. Radiology 2003;226:433–40. [26] Barbalias GA, Liatsikos EN, Kalogeropoulou C, et al. Externally coated ureteral metallic stents: an unfavorable clinical experience. Eur Urol 2002;42:276–80. [27] Kulkarni RP, Bellamy EA. A new thermo-expandable shape-memory nickel-titanium alloy stent for the management of ureteric strictures. BJU Int 1999;83:755–9. [28] Kulkarni R, Bellamy E. Nickel-titanium shape memory alloy Memokath 051 ureteral stent for managing long-term ureteral obstruction: 4-year experience. J Urol 2001;166:1750–4. [29] Trueba Arguinarena FJ, Fernandez Del Busto E. Selfexpanding polytetrafluoroethylene covered nitinol stents for the treatment of ureteral stenosis: preliminary report. J Urol 2004;172:620–3. [30] Borin JF, Melamud O, Clayman RV. Initial experience with full-length metal stent to relieve malignant ureteral obstruction. J Endourol 2006;20:300–4. [31] Liatsikos EN, Kagadis GC, Barbalias GA, Siablis D. Ureteral metal stents: a tale or a tool? J Endourol 2005;19:934–9. [32] Siablis D, Kagadis GC, Liatsikos EN, et al. Ureteral metallic stents: application of virtual endoscopy for ureteral patency control. Int Urol Nephrol 2003;35:327–30. [33] Barbalias GA, Liatsikos EN, Kagadis GC, et al. Ureteropelvic junction obstruction: an innovative approach combining metallic stenting and virtual endoscopy. J Urol 2002;168:2383–6. [34] Kagadis GC, Siablis D, Liatsikos EN, Petsas T, Nikiforidis GC. Virtual endoscopy of the urinary tract. Asian J Androl 2006;8:31–8. [35] Thijssen AM, Millward SF, Mai KT. Ureteral response to the placement of metallic stents: an animal model. J Urol 1994;151:268–70. [36] Desgrandchamps F, Tuchschmid Y, Cochand-Priollet B, Therin M, Teillac P, Le Duc A. Experimental study of Wallstent self-expandable metal stent in ureteral implantation. J Endourol 1995;9:477–81. [37] Hemikoglu B, Men S, Pinar A, et al. Urothelial hyperplasia complicating use of metal stents in malignant ureteral obstruction. Eur Radiol 1996;6:675–81.

CME questions Please visit www.eu-acme.org/europeanurology to answer these CME questions on-line. The CME credits will then be attributed automatically.

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[38] Tunney MM, Keane PF, Jones DS, Gorman SP. Comparative assessment of ureteral stent biomaterial encrustation. Biomaterials 1996;17:1541–6. [39] Liatsikos EN, Siablis D, Kalogeropoulou C, et al. Coated v noncoated ureteral metal stents: an experimental model. J Endourol 2001;15:747–51. [40] Liatsikos EN, Karnabatidis D, Kagadis GC, et al. Application of paclitaxel-eluting metal mesh stents within the pig ureter: an experimental study. Eur Urol 2007;51:217– 23. [41] Laaksovirta S, Talja M, Valimaa T, Isotalo T, Tormala P, Tammela TL. Expansion and bioabsorption of the selfreinforced lactic and glycolic acid copolymer prostatic spiral stent. J Urol 2001;166:919–22. [42] Lumiaho J, Heino A, Pietilainen T, et al. The morphological in situ effects of a self-reinforced bioabsorbable polyactide (SR-PLA 96) ureteric stent: an experimental study. J Urol 2000;164:1360–3. [43] Lumiaho J, Heino A, Tunninen V, et al. New bioabsorbable polyactide ureteral stent in the treatment of ureteral lesions: an experimental study. J Endourol 1999;13:107–12. [44] Isotalo T, Tammela TL, Talja M, Valimaa T, Tormala P. A bioabsorbable, self-expandable, self-reinforced poly-Llactic acid urethral stent for recurrent urethral strictures: a preliminary report. J Urol 1998;160:2033–6. [45] Isotalo T, Talja M, Valimaa T, Tormala P, Tammela TL. A bioabsorbable self-expandable, self-reinforced poly-Llactic acid urethral stent for recurrent urethral strictures: long-term results. J Endourol 2002;16:759–62. [46] Isotalo T, Alarakkola E, Talja M, Tammela TL, Valimaa T, Tormala P. Biocompatibility testing of a new bioabsorbable X-ray positive SR-PLA 96/4 urethral stent. J Urol 1999;162:1764–7. [47] Lam JS, Gupta M. Update on ureteral stents. Urology 2004;64:9–15. [48] Pollak JS, Rosenblatt MM, Egglin TK, Dikey KW, Glickman M. Treatment of ureteral obstructions with the Wallstent endoprosthesis: preliminary results. J Vasc Interv Radiol 1995;6:417–25. [49] Klarskov P, Nordling J, Nielsen JB. Experience with Memokath 051 ureteral stent. Scand J Urol Nephrol 2005;39:169–72. [50] Wright KC, Dobben RL, Magal C, Ogawa K, Wallace S, Gianturco C. Occlusive effect of metallic stents on canine ureters. Cardiovasc Intervent Radiol 1993;16:230–4. [51] Antimisiaris SG, Siablis D, Liatsikos E, et al. Liposomecoated metal stents: an in vitro evaluation of controlledrelease modality in the ureter. J Endourol 2000;14:743–7. [52] Leveillee RJ, Pinchuk L, Wilson GJ, Block NL. A new selfexpanding lined stent-graft in the dog ureter: radiological, gross, histopathological and scanning electron microscopic findings. J Urol 1998;160:1877–82.

1. The clinical outcome after insertion of a urethral MS may be influenced by: A. Anatomic limitation of the prostatic urethra B. Stent material C. Insertion technique D. None of the above

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2. The biodegradation time of the biodegradable materials used in urology is: A. 1 mo B. 13–18 mo C. 2–12 mo D. None of the above 3. The main limitation of ureteral MS insertion is: A. Migration B. Urothelial hyperplasia C. Encrustation D. None of the above 4. Covered MSs were used: A. To overcome the problem of hyperplastic reaction B. For better anchorage

C. To reduce encrustation D. None of the above 5. Drug-eluting MSs have been shown to: A. Be toxic on the tissue B. Reduce migration C. Reduce inflammation and hyperplastic reaction D. Increase inflammation and hyperplastic reaction 6. Insertion of a ureteral MS: A. Can be performed in an antegrade fashion B. Can be performed in a retrograde fashion C. Combination of A and B D. Can be performed with ureteroscopic guidance