Advances in ureteral stent by alphauro

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									Advances in ureteral stent design and construction
The use of urinary stents and catheters has been documented from ancient Egyptian times, when papyrus and lead catheters were used extensively. Ureteral stents are a common tool in today's urologic armamentarium. Since 1978, when Finney developed the modern-day double-pigtail stent,1 there have been many advances that have improved this essential tool. To date, however, there is no ideal stent (Table 1).2 Patients continue to suffer from stent-related morbidity, ranging from irritation and discomfort to sepsis and renal compromise from the encrusted "forgotten" stent. This article reviews recent and future enhancements in stent materials, design, and coatings. STENT MATERIALS A biomaterial is any material, natural or synthetic, that interfaces with human tissue during clinical treatment. Biocompatibility is defined as the utopian state where a biomaterial and the surrounding tissues do not adversely interact with each other. Currently, all existing stent materials have some effect on surrounding tissues (for example, encrustation, biofilm formation, and infection) and are, in turn, affected by their environment.3 Synthetic materials. Polyurethane, silicone, and various blends provide today's mainstay of materials. Polyurethane alone is relatively rigid and uncomfortable, but becomes more comfortable when combined with other materials. Hence, polyurethane blends are the most common synthetic polymer currently used in stents. Silicone, because of its inert nature, is the current "gold standard" stent material in terms of tissue compatibility.4 While the rigidity of silicone stents makes them easy to manipulate in the urinary tract, it may also cause patient discomfort. Proprietary silicone-based stents include C-flex (Cook Urological, Spencer, Ind), Silitek (ACMI Corp, Southborough, Mass), and Percuflex (Microvasive/Boston Scientific, Natick, Mass).

Biodegradable materials. Stents are often placed after endoscopic surgery or in association with shockwave lithotripsy (SWL). If a tether suture is not used, such stents require an additional procedure for removal. This may be so uncomfortable for the patient that an anesthetic is required. This problem has prompted research into creation of a biodegradable stent material as an alternative to existing technology. Biodegradable stents are designed to maintain their integrity for 48 hours, at which time they undergo a dissolution process followed by spontaneous expulsion. The safety of biodegradable stents was tested in a porcine model, where 3 different compositions of a

dissolvable stent were compared with a standard soft hydrogel-coated plastic stent.5 Histopathologic examination of the urinary tract of these animals revealed no difference in inflammatory changes among the various stents after 7 days. In a phase II clinical trial, Lingeman and colleagues placed a proprietary temporary ureteral drainage stent (TUDS, Microvasive/Boston Scientific) in 87 patients after uncomplicated ureteroscopy to facilitate upper tract drainage.6 The primary end point, which was to maintain the stent for at least 48 hours, was reached by 81% of patients. Eight patients had a history of traditional stenting during a prior procedure and completed questionnaires comparing the comfort of the standard stent with that of the biodegradable stent. Using a scale of 1 (extremely uncomfortable) to 10 (very comfortable), the traditional stent received a comfort score of 4.4 and the temporary stent a score of 7.4, indicating that patients found the temporary stent more comfortable. Further efforts are required before this technology can be widely adopted, primarily because of variation in the time to degradation. In the study mentioned earlier, stent fragments were retained longer than 3 months in 3 of the 87 patients, necessitating SWL in 2 and SWL and ureteroscopy in the other.6 In addition, 1 patient underwent proximal migration and another experienced premature expulsion requiring an additional procedure.

pH-sensitive biodegradable materials. Efforts to develop a long-term indwelling, biodegradable stent have used a material that is solid at a normal urinary pH of 5 to 6 (providing drainage), but which dissolves when exposed to an alkaline pH.7 By alkalinizing the patient's urine with oral bicarbonate, the stents dissolved after 24 hours.7 Autologous chondrocyte stents. Amiel and associates fabricated cylinders from polyglycolic acid mesh and seeded bovine chondrocytes onto the tubular scaffolding to create ureteral stents.8 Although this technique is in its infancy, it demonstrates the feasibility of creating an autologous stent, ensuring biocompatibility. This technology would be useful for long-term use in treatment of strictures or ureteral defects. Metal stents. These stents were developed to provide long-term drainage in patients with ureteral strictures or ureteral compression secondary to malignancy. Nickel-titanium (nitinol), widely used for stone-retrieval baskets, is now being utilized in prostatic and ureteral stents.9 This material is thermosensitive—it changes shape depending on temperature. At cool temperatures (approximately 50°F), this material maintains an unexpanded and compact form, allowing the placement of smaller diameter stents that expand to their original shape ("shape-memory") and become softer and elastic when warmed to body temperature. Kulkarni and Bellamy placed 22 nitinol stents in 15 patients with ureteric strictures.10 Prior to insertion, the stents were kept at 50°F to maintain a shaft diameter of 10F. Following balloon dilation of the stricture, each stent was inserted in its unexpanded form through a hollow catheter to the level of the ureteric stricture. Following irrigation with sterile water at a temperature of 122°F, the stents expanded to 20F. There were no reported complications at a mean follow-up of 10.6 months. Retrieved stents displayed epithelialization of the exposed stent surface with normal urothelium.10 Similar studies have demonstrated infection and lumen blockage secondary to overepithelialization, preventing the widespread use of metal stents.9 Future refinements of expandable metal stents are required prior to widespread use in the long-term management of ureteric strictures. Mesh stents. These stents retain shape-memory and have properties similar to metal stents. A braided polyester lattice configuration makes them very lightweight. Their reduced surface area resulted in decreased ureteral inflammation compared with control stents in a study performed in pigs.11 In a small study by Ahmed and colleagues, metal mesh stents were placed to relieve ureteral obstruction secondary to locally advanced prostate cancer in 3 patients.12 The stents were poorly tolerated and all patients required stent removal and nephrostomy tube placement within 3 to 5 months. This technology also requires further improvements to be clinically useful. STENT COATINGS A biofilm is a layer of extracellular matrix, host protein, and glycocalyx that forms on the surfaces of all prostheses within hours of being placed in the urinary tract. The presence of a biofilm allows bacteria to adhere and anchor to the prosthesis, forming a focus of infection. Urinary prostheses left indwelling for lengthy periods are also subject to encrustation. The presence of ureasplitting organisms such as Proteus results in an increased urinary pH, provoking encrustation (calcium phosphate crystallizes more readily at an elevated pH). A variety of coatings have been investigated in an attempt to reduce complications such as infection, biofilm formation, and encrustation, and to modify properties such as lubricity. Hydrogel. This coating consists of hydrophilic polyurethane polymers that swell with water, leading to increased lubricity, facilitating stent placement and a potential improvement in patient comfort. There is evidence that hydrogel coatings resist encrustation, biofilm formation, and infection better than uncoated

polyurethane catheters.13 Polyvinyl pyrollidone, a new hydrophilic coating, has also been shown to prevent biofilm formation and encrustation.14 Heparin. Prostheses coated with heparin have been widely used in interventional cardiology. Heparincoated urologic stents have been shown to resist encrustation and biofilm formation.15 Stents coated with silver nitrate and ofloxacin (Floxin, Ortho-McNeil) have shown similar results,16 but there is little evidence that either of these coatings reduces the incidence of clinically significant catheter-associated infections.17 Oral administration of the fluoroquinolones ciprofloxacin (Cipro, Bayer) and ofloxacin has resulted in levels of antibiotic adsorbed onto the stent surface that is theoretically sufficient to inhibit bacterial growth.18 Clinically, however, this has not proven to reduce colonization and infection. When Riedl and colleagues examined stents in 93 patients, they found that despite antibiotic prophylaxis, 100% of the stents had become colonized with bacteria.19 Phosphorylcholine. This constituent native to the surface of human erythrocytes has been used to coat synthetic polymers to mimic a membrane lipid.20 This coating has been shown to resist encrustation and biofilm formation.20 Encrustation and Oxalobacter formigenes. Encrustation is a common problem with urinary prostheses. Ingested oxalate is metabolized in the gut by the enzyme oxalate decarboxylase, produced by O formigenes. Systemic absorption of oxalate leads to significant levels of oxaluria, which can precipitate with calcium, leading to calcium oxalate crystals in the urine. Theoretically, stents coated with the enzyme could break down oxalate, thus precluding its precipitation and resulting encrustation. Watterson and colleagues coated silicone disks with oxalate decarboxylase and implanted them in the bladders of a rabbit model.21 After an indwelling time of 30 days, the coated disks demonstrated significantly less encrustation than uncoated control disks without any apparent toxicity.21 This technology warrants further study before it can be used in the clinical realm. Drug-eluting stents. In the field of cardiology, drug-eluting stents loaded with compounds such as paclitaxel, sirolimus (Rapamune, Wyeth), and methotrexate have been used in an attempt to prevent arterial restenosis.22 In urology, a similar attempt has been made to thwart urease-producing bacteria that raise urine pH, thus leading to encrustation. Mittelman and associates tested an in vitro model of a stent loaded with the antimicrobial triclosan, and found that it inhibited the growth of P mirabilis and Escherichia coli.23 Antimicrobial-loaded stents may aid in the prevention and possibly the treatment of urinary tract infections as well as provide urinary drainage. Furthermore, they may assist in reducing stent encrustation. Dexamethasone-eluting stents. A drug-eluting metallic ureteral stent with multilamellar liposomes containing entrapped dexamethasone was shown to release 50% of the drug within 48 hours in an in vitro setting of artificial urine.24 Other drugs incorporated into stents or used as a stent coating may be slowly released or "eluted" to help decrease stent-related morbidity. A study of comfort and stent symptoms was recently performed in patients who received an intravesical instillation of ketorolac following stent placement.25 Stent symptoms were reduced compared with controls, suggesting that stents loaded with analgesics may improve patient comfort. STENT DESIGN Changes in stent design have been investigated in an attempt to reduce stent migration, facilitate drainage, and improve patient comfort.

Dual durometer and tail stents. Stents like the Polaris (Microvasive/Boston Scientific) and Sof-Curl (ACMI Corp), known as dual durometer stents, use a softer material in the bladder curl than in the kidney curl. Tail stents have a diameter of 7F at the proximal end, tapering to a soft, lumenless 3F tail at the bladder. Both of these designs are thought to be less irritative to the bladder. A study by Liatsikos and colleagues suggests that tail stents are more comfortable than double-pigtail stents.26 Dual durometer and tail stents both possess a hydrophilic-bonded hydrogel that decreases friction and facilitates stent placement. Spiral stents. In an attempt to improve drainage in cases of chronic ureteral obstruction, a spiral design was investigated that would prevent kinking and compression. Stoller and colleagues reported on a spiral stent (Spirastent, Urosurge Inc, Coralville, Iowa) composed of a soft polyurethane-based material and with metal wire helical ridges on its exterior that spiral down its length.27 The spiral stent displayed greater drainage both around the stent and through the ureter compared with regular stents in an in vitro model.27 Other design features. A stent designed by Taylor and McDougall has a metal bead attached to the bladder end to facilitate removal.28 A special catheter is inserted with a magnet to retrieve the stent, precluding cystoscopy. Lighted stents have been used to help general surgeons identify the ureters during laparoscopic colectomy to avoid potential ureteric injury.29 Application of this stent may also extend to gynecologic and urologic procedures. FUTURE ADVANCES An intravascular stent was recently designed to deliver local gene therapy to arterial walls.30 This concept may be transferable to ureteral stent design for the treatment of cancer and stricture disease. As drug-eluting and coating technologies continue to improve, we will likely see them combined with the latest antimicrobial, analgesic, and anti-encrustation compounds to improve the comfort and decrease the morbidity of ureteral stents. Patient discomfort remains a significant problem with the current generation of ureteral stents, and may require radical changes in stent design. Ongoing research into biomaterials and biocompatibility is essential to continue improvements to this essential urologic tool. As new technologies are developed, they should be assessed with randomized trials using validated questionnaires.

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