Surface science techniques were used to study three stent types after use in patients. The stent type, duration of insertion and age or sex of the patient did not correlate significantly with the amount of encrustation (Wollin et al., 1998). However, it has been suggested that factors which affect the amount of encrustation include the composition or the urine, the type of invading and colonizing bacteria and the structure and surface properties of the biomaterial used (Gorman 1995). A low surface energy surface seems to resist encrustation compared with a high surface energy surface (Denstedt et al., 1998).
Many different types of stone can form in the urinary tract. Calcium oxalate, calcium phosphate, uric acid and cystine stones are metabolic stones because they form as a result of metabolic dysfunction. They usually are excreted from the urinary tract. Struvite (magnesium ammonium phosphate) and hydroxyapatite (calcium phosphate) are associated with infection (infection stones). These account for 1520% of urinary calculi. ESWL is used to break up the larger infection stones because they don't pass; recurrence of the problem occurs with incomplete removal. Infection stones can manifest as poorly mineralized matrix stones, highly mineralized staghorn calculi or as bladder stones which often form in the presence of ureteral stents. Urea-splitting bacteria colonize the surface and cause alkalinization of the urine, which lowersthe solubility of struvite and hydroxyapatite, and they deposit on thesurface. Bacterial biofilm associated with encrustation is a commonclinical occurrence. (Gorman and Tunney, 1997). It has been suggestedthat prevention of bacterial colonization would prevent encrustationbecause of their ultimate responsibility for its formation (Bibby et al.,1995).An in vitro model was developed that produces encrustationsimilar to those seen in vivo (Tunney et al., 1996a). An experiment wasconducted to compare the encrustation potential of various ureteral stentmaterials. The long-term struvite and hydroxyapatite encrustation ofsilicone, polyurethane, hydrogel-coated polyurethane, Silitek andPercuflex were compared. All of the materials developed encrustation,however, it was found by image analysis that the rates of encrustationvaried on the different materials. Silicone had less encrustation (69% at10 weeks) compared to the other materials (1 00%) at the same time point(Tunney et al., 1996b). Continuous flow models have also been developedwhich are more representative of conditions in the upper urinary tract.They are discussed by Gorman and Tunney, (1 997).Efforts to reduce encrustation using new materials, smoothersurfaces and hydrogel coatings have been attempted. A hydrogel-coatedC-flex stent (Hydroplus, Boston Scientific) was shown to have lessepithelial cell damage and encrustation than other biomaterials and wasrecommended by the investigators for long-term use (Cormio, 1995). Inaddition, a poly(ethy1ene oxide)/polyurethane composite hydrogel(Aquavenem, J & J) resisted intraluminal blockage in a urine flow model
An in vitro model was developed that produces encrustation similar to those seen in vivo (Tunney et al., 1996a). An experiment was conducted to compare the encrustation potential of various ureteral stent materials. The long-term struvite and hydroxyapatite encrustation of silicone, polyurethane, hydrogel-coated polyurethane, Silitek and Percuflex were compared. All of the materials developed encrustation, however, it was found by image analysis that the rates of encrustation varied on the different materials. Silicone had less encrustation (69% at 10 weeks) compared to the other materials (1 00%) at the same time point (Tunney et al., 1996b). Continuous flow models have also been developed which are more representative of conditions in the upper urinary tract. They are discussed by Gorman and Tunney, (1 997). Efforts to reduce encrustation using new materials, smoothersurfaces and hydrogel coatings have been attempted. A hydrogel-coated C-flex stent (Hydroplus, Boston Scientific) was shown to have less epithelial cell damage and encrustation than other biomaterials and was recommended by the investigators for long-term use (Cormio, 1995). In addition, a poly(ethy1ene oxide)/polyurethane composite hydrogel (Aquavenem, J & J) resisted intraluminal blockage in a urine flow model compared with silicone and polyurethane (Gorman et al., 1997a). Anotheradvantage with Aquavene is that it is rigid in the dry state, whichfacilitates insertion past obstructions in the ureter and becomes soft onhydration providing comfort (Gorman and Tunney, 1997). Gorman et al.(1 997b1997b) concluded that the chance of stent fracture would be reduced ifthe ureteral stent side holes were eliminated.Urinary tract infection is another common major problem with theusage of ureteral stents. Initially, a conditioning film is deposited on theureteral stent surface. The film is made up of proteins, electrolytematerials and other unidentified materials that obscure the surfaceproperties of the stent material. Electrostatic interactions, the ionicstrength and pH of the urine and differences in fluid surface tensions affectbacterial adhesion to the conditioning film. Subsequently, a microbialbiofilm forms over time. The biofilm is composed of bacterial cellsembedded in a hydrated, predominantly anionic mixture of bacterialexopolysaccharides and trapped host extracellular macromolecules. ====Obstruction====Obstruction of urine flow and urinary tract sepsis can result in continuedgrowth of the biofilm. Colonization of devices implanted in the urinarytract can lead to dysfunction, tissue intolerance, pain, subclinical or overtinfection and even urosepsis. Device related infections are difficult totreat and device removal is usually necessary. The biofilm has been foundto impede the diffusion of antibiotics; in addition, the bacteria in thebiofilm have a decreased metabolic rate , which also protects them againstthe effects of antibiotics (Wollin et al., 1998).Riedl, et al. (1 999) found 100% ureteral stent colonization rates inpermanent and 69.3% in temporary stents. Antibiotic prophylaxis did notprevent bacterial colonization and it was recommended that it not be used.On the other hand, Tieszer, et al. (1 998) believe that fluoroquinolones canprevent infection. They also have found that some stents have denserencrustation than others, however, the stent material did not change theelements of the "conditioning film" adsorbed or alter its receptivity to
bacterial biofilms.
The predictive value of urine cultures in the assessment of stent
colonization was examined in 65 patients with indwelling ureteral stents.
It was found that a sterile urine culture did not rule out the stent itself
being colonized (Lifshitz, et al., 1999). Patients with sterile urine culture
may benefit from prophylactic antibiotics; however, the authors contended
that the antibiotics must work against gram-negative uropathogens and
gram-positive bacteria including enterococci.
It is obvious that there is controversy in the literature whether
prophylactic systemic antibiotics are useful with ureteral stent implant.
However, antibiotics do not seem to prevent stent colonization. Denstedt
et al. (1998) have found that ciprofloxacin, with a 3 day burst every 2
weeks, actually is adsorbed onto the stent which makes longer term
treatment possible with reduced risk of bacterial resistance. There has
been research targeted at coating or impregnating urinary catheters with
====Infection====The predictive value of urine cultures in the assessment of stent colonization was examined in 65 patients with indwelling ureteral stents. It was found that a sterile urine culture did not rule out the stent itself being colonized (Lifshitz, et al., 1999). Patients with sterile urine culturemay benefit from prophylactic antibiotics; however, the authors contended that the antibiotics must work against gram-negative uropathogens and gram-positive bacteria including enterococci.It is obvious that there is controversy in the literature whether prophylactic systemic antibiotics are useful with ureteral stent implant. However, antibiotics do not seem to prevent stent colonization. Denstedt et al. (1998) have found that ciprofloxacin, with a 3 day burst every 2weeks, actually is adsorbed onto the stent which makes longer term treatment possible with reduced risk of bacterial resistance. There has been research targeted at coating or impregnating urinary catheters with antimicrobials and products are on the market, however, there are noantimicrobial ureteral stents approved by the FDA. === The need ===It is clear that there is a need for a new material that will be able toresist encrustation and infection in the urinary tract.According to Merrill Lynch, ureteral stents represent an $80 MMUS market. Boston Scientific is in the lead with -~50% of the marketfollowed by Maxxim (Circon), Cook and Bard is a smaller player. Thereare a number of other small contenders.The use of ureteral stents is increasing; the indications for ureteralstenting have broadened from temporary or permanent relief or uretericobstruction to include temporary urinary diversion following surgicalprocedures such as endopyelotomy and ureteroscopy and facilitation ofstone clearance after ESWL (Tolley, 2000). The use of ureteral stents forpatients having ESWL for renal calculi is however controversial andseems to be related to the size of the stones and invasiveness of theprocedure. According to survey results reported by Hollowell, et al.(2000), there is a significant difference in opinion concerning the use ofstents with ESWL. The number of ureteral stents used in patients withstones 2 cm or less treated with ESWL is significant in spite of the lackscientific evidence in support of this practice. Of 1,029 urologistsreturning surveys, for patients with renal pelvic stones 10, 15 or 20 rnmtreated with ESWL, routine stent placement was preferred by 25.3%,57.1 % and 87.1 %, respectively. Urologists recommend usingureteroscopy rather than ESWL for distal ureteral calculi 5-1 0 mm.
1.2 Fit with Gore Corporate Strategy
+ This product fits into Gore's DSP market segment