Ureteral stents are the most commonly used tool in the treatment of various benign and malignant urological conditions. However, the use of stents is often accompanied by complications such as crust formation, infection, pain, discomfort after placement, stent migration or failure, etc.
In recent years, drug-eluting stents and naturally degradable stents have been studied with great progress, and new engineering techniques have been applied to these studies.
Today’s double J ureteral stent was first introduced by Finney et al. in 1978, and since then ureteral stent placement has become a routine urologic procedure. Ureteral stents are mainly used as an adjunct to urolithiasis to relieve various benign and malignant obstructions, to promote ureteral recovery and to treat urinary extravasation.
In addition, preoperative ureteral stent placement facilitates intraoperative determination of the ureteral position. However, despite the widespread use of ureteral stents, their more frequent complications are a concern. The most common complications include infection, skin crust formation, and post-tubing discomfort. An in-depth understanding of these complications requires a study of stent design and how to improve clinical stent use.
Stent-related complications
1. Post-stenting discomfort
The most common complication of stent placement, whether acute or chronic, is the discomfort associated with the stent. To better understand this issue, Joshi and colleagues designed the Ureteral Stent Symptom Questionnaire (USSQ) to quantify post-stenting discomfort in patients with urolithiasis and benign obstruction.
This study was the first to assess the range of post-stenting discomfort problems, providing a standardized scale. The study showed that more than 80% of patients with benign lesions stented had irritative voiding symptoms, pain, and discomfort. This discomfort was not limited to urinary tract symptoms, but also included the entire torso, which greatly affected daily function.
In a later study, the USSQ evaluated the relationship between the position of the distal stent ring in the bladder and post placement discomfort and found that those patients whose distal stent ring crossed the bladder midline showed more problems on the USSQ after 7 and 28 days of placement.
A subsequent randomized trial examining the location of the distal stent ring showed that a stent that was too long in the bladder caused severe urinary difficulty, urinary urgency, and a greater impact on quality of life. Pain is exacerbated during voiding and can radiate to the ipsilateral torso, which may be secondary to ureteral pressure reflux and stent movement.
Previous studies have shown that stents can move about 2 cm during daily activities, causing physical irritation of the ureter, resulting in inflammation of the urethral epithelium of the bladder and kidney where the stent ring is located, and therefore may cause additional pain and discomfort. Future studies should focus on the design of the stent and the choice of biomaterials, which may reduce irritation in cases where stent movement is unavoidable.
2. Loss of ureteral peristalsis
It is now widely believed that stents can affect ureteral peristalsis by inducing excessive peristalsis in the ureter over a period of time. For a short time after stent placement, the ureter will peristaltically move excessively to clear the stent (due to partial obstruction) and eventually the peristalsis disappears.
Whether this state of peristaltic disappearance itself is associated with pain and discomfort is unknown, but some studies suggest that the urinary tract slows down the voiding process as a result, which may also account for the mild ipsilateral pelvic effusion that occurs after tube placement.
Interestingly, patients’ pain and urinary symptoms are significantly reduced with selective alpha-blockers such as tamsulosin, which inhibits ureteral constriction and reduces peak ureteral systolic pressure. Similarly, alfuzosin significantly improves urinary tract symptoms and somatic pain, especially in urination and ipsilateral somatic pain.
Whether this reduction in symptoms is due to loss of peristalsis due to inhibition of ureteral contraction by alpha-blockers or due to recovery of peristalsis following the easing of a sustained state of ureteral smooth muscle contraction caused by stent placement is unclear.
If the latter is correct, then maintenance of ureteral peristalsis after stenting is beneficial, while reducing pelvic effusion due to previous loss of peristalsis. Future studies are needed to better understand whether loss of ureteral peristalsis is a beneficial outcome of stent placement and whether maintenance of peristalsis improves the overall function of the stent.
3. Stent displacement
Stent displacement, especially end displacement and detachment, is not uncommon. A variety of factors are involved in this process, including stent length, material, and diameter. It has been shown that silicone stents with a diameter of 4.8 Fr are more prone to distal displacement than polyurethane stents with a diameter of 6 Fr.
Patient-related factors are stent implantation time and kidney motion with respiration, but these factors still need to be studied in more depth. Although the appropriate length of the stent is determined by the patient’s height, studies have shown that a more applicable distance between the ureter and the renal pelvis and bladder junctions reduces the frequency of distal displacement.
Distal stent displacement can offset the benefits of stenting and exacerbate stent-related symptoms. However, this can be easily adjusted by cystoscopy. What is challenging is the uncommon proximal stent shift, the incidence of which has been reported to be 1-4.2%. Management of proximal stent displacement requires retrograde stent removal via ureteroscopy.
When the distal stent ends below the pelvic rim, stent removal using a lithotomy basket or Fogarty catheter has a success rate of >90%. Special cases of proximal displacement include stent proximal displacement above the pelvic rim, above the stenotic segment or the site of recent surgical repair. In these cases, the percutaneous approach has a higher success rate.
4. Urinary tract infection
Bacterial colonization of ureteral stents is a significant problem, with reported colonization rates of 42-90%. Although bacteria are able to interact and adhere to the bare stent surface, this direct interaction does not appear to be the primary mechanism of bacterial adhesion and colonization.
Recent studies have shown that urinary conditioned membranes can alter the physical properties of the scaffold surface. Bacteria express a protein called adhesin, which recognizes and adheres to proteins forming the major component of urinary biofilms.
A long-standing hypothesis that the presence of such membranes increases bacterial adhesion was tested by Elwood et al. in 2013, who found no difference in adhesion and colonization of Escherichia coli and Staphylococcus compared to scaffolds containing conditioned membranes versus those that did not.
Their findings refute the hypothesis that urinary conditioned membranes increase bacterial adhesion and colonization and also suggest that preventing the deposition of these membranes does not inhibit bacterial adhesion and colonization, as the bacteria appear to act only on the bare scaffold surface.
Interestingly, despite a 90% incidence of stent bacterial colonization, only a small percentage of patients with positive stent cultures develop symptomatic urinary tract infections. The incidence of urinary tract infections increased when stents were placed for longer than 90 days.
In a continuous survey of 250 patients, urine cultures before and after placement, and bacterial cultures at the tip of the distal stent showed that time of stent placement, systemic disease, including diabetic nephropathy and chronic renal failure without dialysis (blood creatinine of 200-500 μmol/l) were significantly associated with bacteriuria and bacterial stent colonization.
Considering the increased risk of urinary tract infections, the authors recommend a shorter duration of stent placement and prophylactic antimicrobial therapy for high-risk patients. However, in this regard, it is important to consider that those patients with systemic disease are at a much higher risk of carrying antibiotic-resistant strains due to their prior antimicrobial therapy. Therefore, efficient antibiotic prophylaxis regimens must be patient-specific and must carefully consider the patient’s medication history and prior antibiotic use.
Currently, urine culture is the most commonly used method to detect bacterial colonization and infection status of stents after placement. However, a negative urine culture does not mean that the stent is free of colonization, as the sensitivity of urine culture for detecting stent colonization is only 21-40%, but increases with the duration of placement.
In fact, the rate of positive urine cultures (despite positive stent cultures) is relatively low within a short period of placement. This suggests that the bacteria colonizing the stent have not yet infected the urine, but that they have infected the stent during stent placement.
In addition, the species of bacteria in the urine is usually different from the species found on the stent. The species of bacteria on the stent varied with the segment in which the stent was tested. These findings reveal the fact that, similar to the biofilm found on Foley catheters, the membranes found on ureteral stents often consist of multiple Gram-positive and Gram-negative bacteria, making antibiotic therapy against a single urine culture ineffective.
5. Stent cortical formation
Similar to bacterial colonization, the occurrence of stent crust formation increases with time of placement. In patients with urolithiasis with stent placement, the incidence of crusts was 9.2% for stent removal within 6 weeks, 47.5% for removal within 6-12 weeks, and up to 76.3% for removal after 12 weeks.
Although the number of crusts appeared to be higher in the proximal and distal convoluted portions, the portion of the ureteral lumen was usually clearer or the last to form crusts. This may be due to the “clearing” effect of ureteral peristalsis, while the coiled portion of the stent is in constant contact with urine in the kidney and bladder.
The process of crust formation is very complex, and despite the application of multiple materials with different physical properties, none of them can prevent the deposition of crystals and eventually lead to crust formation. Of all the materials available, silica gel is the least likely to form guano and hydroxyapatite crusts.
It is important to note that the extent to which a material forms a crust depends largely on the test equipment used. Often the anti-crust formation characteristics of materials claimed by some companies are based on simple in vitro experiments only and do not describe what happens to these materials in patients.
While simple in vitro experiments can demonstrate that those materials and/or coatings may resist crust formation, the actual elaboration of their function in clinical applications can only be based on relevant in vivo animal models or clinical trials.
Although the exact mechanism of stent crust formation remains unclear, most believe that crust formation is secondary to the formation of a stent urine biofilm. Biofilm formation begins when urinary proteins are electrostatically adsorbed onto the surface of the stent biomaterial.
Interestingly, because the crust does not form instantaneously, most stents detach the hydrophilic shell from the surface within a short time after implantation, and this shell prevents biofilm formation. Thus, constant changes in the physical properties of the stent surface are beneficial in preventing biofilm deposition and subsequent crust formation.
One study showed that the crustal composition of the stent was identical to the composition of the concurrent stones. It is obvious that they are both infiltrated in the same urine and the same composition is supersaturated to form stones. Whether the crystals act and adhere directly to the stent material, and whether they are more tightly adherent through interaction with the biofilm component, is not known.
Two studies analyzed the composition of biofilms on the surface of scaffolds with and without crust formation. Overall, over 300 proteins were found to be present on the scaffold surface. Ig κ, IgH G1, α1 antitrypsin, histone H2b and H3a were highly associated with scaffold shell formation, while uromodulin and histone H2a were less associated.
The authors hypothesized that these positively charged proteins may attract negatively charged crystals and form a skin shell. Another study suggested a different mechanism. He detected that scaffold biofilms contain calcium-binding proteins, such as urinary regulator and S-100 protein. These proteins allow calcium-containing crystals to adhere to the surface of the scaffold. This study also identified the presence of blood proteins such as plasma albumin, globulin and fibronectin. These proteins in the stent biofilm can interact with hydroxyapatite via electrostatic forces, suggesting another mechanism for stent cortical formation.
Even when stents are placed for a moderate period of time (less than 8 weeks), crust formation remains common. Severe crust formation increases the difficulty of stent removal, potentially requiring multiple procedures. To guide the management of stent crusts, Acosta-Miranda et al. established the Forgotten, crust-forming and calcified (FECal) stent grading system based on their clinical experience with these problems. Stents are graded according to the area of crust formation, and each grade has a corresponding therapeutic measure.
In the system, grade 1 crust formation affects only the distal stent convolutions, grade 2 is associated with crust formation in the proximal convolutions, grade 3 includes crust formation in both grade 2 and the ureteral portion of the stent, grade 4 shows crust formation in both the distal and proximal convolutions, and grade 5 shows crust formation in the entire stent.
This grading system reflects the increasing difficulty of stent removal with increasing grading. grade 5 stent crusts are associated with a duration of placement greater than 2 years, which usually occurs in patients who forget to remove the stent. grade 4 and 5 crusts often require multiple extraction procedures (1.94-2.7).
The authors also noted that removal of stones from the distal portion of the stent prior to treatment of the proximal portion could increase the success rate of extraction. Some authors recommend preoperative nephrograms to confirm the function of the renal unit, because in patients with poor renal function, management of severe stent crusts may require ureterectomy and open bladder lithotripsy.
Prolonged stent placement makes the occurrence of grade 4 and 5 conditions in the FECal grading system inevitable, which typically occurs in patients who forget the time of extraction. To reduce the occurrence of grade 4 and 5 stents, some research groups have recommended the use of electronic stent registries (ESRs) to enter stent information, including time of placement and expected time of removal, into the patient’s electronic medical record (EMR).
The ESR system should alert the physician before the expected time of removal, and the physician should also be alerted when a stent change is not recorded in the EMR or when the removal record is deleted. This system has significantly reduced the incidence of forgotten stent removals, from 12.5% to 1.5% after one year, which provides strong support for the use of this system in urology.
Overcoming complications
1. Metal stents resist extrinsic compression
To overcome the disadvantages of polymeric ureteral stents, such as regular replacement, obstruction of the stent and failure due to the inability of extrinsic compression to function, researchers invented metallic stents (Figure 1). These stents were configured with both self-expanding and conventional double-J stent configurations.
One of these double-J metal stents is called the Resonance stent (Resonance?) and consists of a nickel-cobalt-titanium-molybdenum alloy that is closed at both ends. five years of experience with the Resonance stent was published in a 2013 study, a cohort study that included 47 patients with a total of 139 metal stents used to treat chronic ureteral obstruction due to benign and malignant disease. This is the most complete report on the use of metal stents.
The average duration of induction was 8 months, with a failure rate of approximately 28% due to pain, progression of renal insufficiency, recurrence of urinary tract infection, stent displacement, progression of hydronephrosis, hematuria, lower urinary tract symptoms and/or crust formation. Although for most individuals, complications are significant in terms of overall patient and stent function, the use of metal stents is an appropriate option for both benign and malignant disease.
A long-term follow-up study of self-expanding metal stents was recently published. 2009, an 11-year follow-up study analyzed a thermally expanded metal stent called Memokath?051. Despite complications such as stent migration, crust formation, and fungal infection, the authors concluded that this new self-expanding metal stent was effective in reducing ureteral obstruction in the long term and could be a safe alternative to conventional double J stents.
Similarly, another study in 2000 reported experience with a self-expanding metal stent in 90 patients with malignant ureteral obstruction. The most common complications included stent displacement, proliferative reaction, crust formation, or inward tumor growth.
Interestingly, in some patients secondary interventions did not guarantee ureteral patency and required double J-tube or external stent placement. The authors conclude that tract metal stents can relieve the compression of the upper urethra by extraureteral obstruction for a prolonged period of time in selected patients.
In contrast to self-expanding metal stents, there have been few studies of balloon-expandable metal stents. A study of 12 patients with malignant ureteral obstruction found both balloon-expandable (n=6) and self-expanding (n=6) metal stents to be safe and effective. Another study of 9 patients with benign or malignant ureteral obstruction compared the use of self-expanding stents (n=8) to balloon-expanding stents (n=1). Overall, all patients maintained ureteral opening with no complications.
The authors claim that these metal stents can be a safe and effective alternative to conventional double J-tubes. To date, no large-scale, long-term studies have examined the effectiveness of these metal stents in the ureter. More of these studies are needed before they can be recommended for the treatment of ureteral obstruction.
Figure 1 Appearance and placement of ureteral metal stents. a. Double J stent tubes can be made of metal or plastic and are placed in the center of the lumen with the help of a propeller and a metal guidewire. The balloon is removed and the stent tube is placed in direct contact with the wall. c. Self-expanding Memokath® 051 stent placement requires a guidewire, sheath and insertion system. Once placement is complete, direct contact with the tube wall can be made under flushing with hot sterile urine.
2. New metal stent design
Research on ureteral stent design has focused on the development of new stents that can overcome the above-mentioned disadvantages of metallic and polymetallic stents. The new stents that have received the most attention are more flexible and drug-eluting metal stents, and stents made of naturally degradable materials.
(1) Flexible metal stents
How to improve the comfort of metal stents is a hot research topic. A more flexible stent design allows the stent to adapt to the shape of the ureter as the patient moves. The recent Passage? stent is a metal coil stent configured with a spiral coil-like structure that increases both the flexibility and the radial compression resistance of the stent.
Unlike the Resonance? stent, which is tightly wound with stainless steel guidewires, the Passage? and Snake stents are not tightly wound and are open at both ends, which increases the flexibility and patient comfort of the stent. One study showed that the Passage and Snake stents had significantly reduced tensile strength and higher radial compression resistance compared to the Resonance and Silhouette stents.
The lower tensile strength is an important factor in patient comfort, and it also prevents the stent from shifting. The increased radial compression resistance prevented inward tumor growth or obstruction due to stent compression. Interestingly, the polymorph coating on the 7Fr Snake stent increased the tensile strength of the stent and decreased the radial compression resistance. This finding suggests that the thickness of the stent determines its compressive strength more than its construction and design.
The authors speculate that the 6Fr stent may be more effective than the larger 7 Fr stent in reducing extrinsic ureteral obstruction. It remains to be seen whether newer, more flexible metal stents will improve overall patient comfort.
(2) Drug-eluting metal stents
To overcome metal stent complications such as restenosis, some institutions have investigated drug-eluting self-expanding metal stents. This stent has been used in other medical fields such as coronary and vascular disease, where it has been used to prevent restenosis of the lumen. Preclinical and clinical studies have found limited efficacy of drug-eluting conventional double J ureteral stents, possibly due to low ureteral tissue drug concentrations. Drug transport in self-expanding stents is similar to that in cardiology with higher efficacy compared to conventional metal stents.
Their mechanical scaffold-like expansion ensures that the drug can be released in close proximity to the tissue. The first relevant study to examine the efficacy of paclitaxel-eluting metal stents in pigs found that 21 days after placement, most bare metal stents were occluded or stenosed due to a proliferative response, while ureters with drug-eluting stents present remained open.
Another study used porcine and rabbit models and showed that zotamox-eluting metal stents prevented the onset of ureteral occlusion after more than 8 weeks of placement.
Both of these studies provide a successful case for the use of expandable drug-eluting metal stents in stopping ureteral obstruction (caused by stent-induced tissue proliferation). Considering that most metal stents are used to treat malignant ureteral obstruction, and that malignant tissue may not respond in the same way as normal tissue, further evaluation of the efficacy of these stents in similar settings is needed.
In addition, dilating stents, unlike double J stents, support the ureteral wall and interact directly with ureteral tissue, which may cause potential injury and ureteral dysfunction. Therefore, the effect of dilating stents on the physiological function of the ureter also needs to be studied in depth.
3.Naturally degradable stents
Natural degradable stents can overcome some stent-related complications and are the most popular type of stent design. Resorbable stents can reduce the occurrence of stent-related complications associated with the extraction of polymorphic stents or forgotten stents. The natural degradable stent has more benefits than the resorbable stent. The physical properties of its surface change as the stent degrades, which can reduce bacterial action and adhesion, reduce biofilm deposition and crust formation.
Natural degradable stents are more comfortable for the patient because of their softer material. Other advantages include early degradation of the convoluted portion of the bladder, which can reduce bladder irritation and the occurrence of vesicoureteral reflux during urination.
The main naturally degradable materials include polyglycolic acid, polylactic acid, polylactic acid – glycolic acid copolymers and alginates. Early knowledge of naturally degradable stents involved the fact that degradation could be controlled pharmacologically, in that the pH of the urine could be changed depending on the time of stent placement to induce degradation.
In vitro tests found that such materials degraded within 48 hours at pH <7 ph="">7. Although it is tempting to control the degradation of the scaffold by changing the urine pH, there are many limitations to the application of this method. This is because the change in urine pH can lead to excessive crystallization.
(1) Preclinical studies
Polylactic acid (PLA)-glycolic acid copolymer-based scaffolds have shown early success in animal models, but have not been further developed. For example, in two studies, the degradable PLA scaffold possessed good drainage characteristics and anti-reflux properties, but its efficiency of degradation and biocompatibility were low.
In contrast, in trials using dogs as a model, these stents were found to be completely dissolvable after 12 weeks, with better biocompatibility than conventional plastic stents. In addition, polylactic acid stents were effective in preventing hydronephrosis in a dog ureteral injury model.
Researchers examined the function of polylactic acid-hydroxyacid copolymer stents in a porcine model of pyelotomy and found that they had good radiographic and drainage properties, but their poor biocompatibility limited their further development and application.
Another study showed no complications with the use of poly(lactic acid)-glycolic acid copolymer scaffolds after paracentesis pyelotomy. In a porcine model, a shortened spiral stent made of the same material showed superior drainage and anti-reflux properties, but was not specifically tested for biocompatibility.
(2) Clinical studies and current developments
A large clinical study is currently evaluating the role of a temporary ureteral drainage stent made of alginate polymer, which has been shown in phase I and II clinical trials to promote urinary drainage with good compatibility and safety. The stent was designed to be present for at least 48 h before degradation, but inadequate degradation in some patients may result in the need for secondary removal of undissolved fragments.
The median time to stent degradation was 15 days. In three patients, residual fragments were present for more than 3 months and eventually required extracorporeal shock wave lithotripsy and ureteroscopic treatment for removal. Although there was concern about the potential for stone formation due to residual fragments