Impact of Colloidal Fluid on Stent Failure Under Extrinsic Ureteral Obstruction: An In Vitro Experimental Study

Introduction

Extrinsic ureteral obstruction (EUO) is usually caused by pelvic malignancies or metastases leading to hydronephrosis and renal failure. Drainage of the obstructed kidney under such circumstances is imperative to preserve renal function and facilitate chemotherapeutic treatments, and ureteral stents are employed commonly. These ureteral stents often fail, caused by what is usually attributed to external pressure over the ureter occluding the stent lumen.

Indeed, high rates of stent failure (defined as the inability of fluid to pass through a stented ureter) due to EUO have been well recognized decades ago, ^1,2 yet little direct investigation of related risk factors has been reported.

Most existing studies of stent failure under EUO have focused on in vitro analysis of the effects of direct mechanical compression on stents and its presumed, potential, or actual role in stent failure. ^{3 –6} However, as shown by Shilo et al., ⁷ deformation and compression of the ureter alone, particularly under realistic degrees of compression, cannot generally account for the high incidence of failure of a stented ureter in clinical practice. Rather, we suggested that other factors, particularly the presence of colloids in the urine, may play a critical synergetic role with deformation and compression in stent failure.

Two key points of speculation are raised by Docimo and Dewolf ¹ : they suggested (on the basis of analysis of stent properties, patient histories, and stent failure statistics) that stent obstruction/failure due to an EUO is caused by accumulation of debris in the urine, and as a consequence, they suggested that it is preferable to use the maximal stent diameter to reduce the likelihood of stent failure. In the current study, and based on the investigation by Shilo et al., ^7,8 we examine these points in a systematic analysis with in vitro experiments. In this study, we use the term “colloid” to denote any type of debris in urine.

We evaluated the efficacy of different ureteral stent diameters under EUO in the presence of colloids. Building on the experimental protocols and insights reported by Shilo et al., ⁷ we developed an in vitro experimental setup of a stent within a ureter to investigate the effect of colloids on stents that are simultaneously subjected to ureteral deformation and compression.

Materials and Methods

Experimental setup

To examine an EUO, two structural features affecting the stented ureter must be considered, namely deformation and compression. Deformation refers to the overall curvature of the stented ureter caused by the presence of the EUO, while compression represents the potential partial (or full) closure of the stented ureter by reduction in diameter and/or change in (circular) cross section in the direct vicinity of the EUO. Building on the experimental design for the in vitro setup of a single stented ureter subjected to EUO, ⁷ we developed a system to enable simultaneous experimentation with 12 stented ureter units. We first describe a single in vitro stent–ureter–kidney–bladder unit and then the 12-unit system.

Each stented ureter unit consists of a stent placed within a natural latex rubber tube that simulates a ureter, connecting a renal unit to a bladder unit, as shown schematically in Figure 1. A latex tubing (NEWTEX, NewAge^® Industries, Inc.), with an inner diameter of 3.175 mm and wall thickness of 0.79 mm, was determined (in comparison with several types of tubing) to feel most similar to the human ureter upon testing by different senior urologists. The use of latex tubing to mimic a ureter without peristalsis can be justified, further noting that stenting generally results in a pronounced reduction of ureteral peristalsis, ⁹ while accumulation of extracellular collagen in dilated ureters can lead to increased wall stiffness and reduced distensibility. ¹⁰

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FIG. 1.

Schematic showing the experimental setup, with details of a single ureter–stent unit (including the angle of deformation, θ°).

Experiments were carried out using Double-J (pigtail) stents (Boston Scientific^® Percuflex Plus) with 4.8F, 6F, 7F, and 8F diameters. The proximal pigtail end was inserted into a glass vessel representing a renal unit (volume ∼25 mL), while the distal pigtail was removed so that the stented ureter drained freely into a glass vessel representing a bladder unit (volume ∼30 mL). Note that the distal pigtail is not expected to have any effect on the dynamics investigated here given that the focus is on fluid and colloid flow dynamics from the inlet and through the critical region in the vicinity of the EUO-induced deformation and compression.

A piezometer connected to the renal unit allows measurement of pressure changes within the entire stented ureter system; the height of the outlet from the bladder unit is fixed to maintain a fully saturated system and stable piezometer measurements over time. The region of deformation and compression is established by passing the stented ureter through a molded, curved screw clamp design that controls the angle of deformation (set at θ = 40°, as shown in Fig. 1) and compression (set at 2000 g (≈19.6 N) over the clamped arc, about 3.5 cm in length, located in the region of maximum deformation). The clamping pressure was confirmed using a force meter (Lutron, Model FG-5000A). The angle of deformation and compressive pressure were prescribed on the basis of the analysis by Shilo et al. ⁷ Stented ureter units with no deformation or compression were also employed as controls for the experiments to clearly separate the effects of colloidal flow from those with synergy between deformation/compression and colloidal flow.

The 12-stent system is shown schematically in Figure 2a and as a photograph in Figure 2b. This system consists of 12 of the units shown in Figure 1. The units are placed within a temperature-controlled chamber, with two thermostat units that maintain the environment at 37°C. A large reservoir (6 L) supplies the colloidal solution to a smaller reservoir within the chamber, which then feeds each of the 12 units separately through a 12-channel peristaltic pump (Ismatec^® Model IPC 12-channel pump). The fluid volume in the renal unit damped small pressure fluctuations induced by the pump.

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FIG. 2.

(a) Schematic showing the experimental setup, with details of the 12-stent system with replicate and control (no deformation or compression) units. (b) Photograph of the full experimental setup, with (left to right) two replicate units each of 4.8F, 6F, 7F, and 8F stents under deformation and compression and one control unit of each stent size with no deformation or compression (straight).

Results

First, in a preliminary analysis using the experimental setup and protocol of Shilo et al., ⁷ we confirmed that the 8F stent shows absolutely no decrease in flow (or increase in renal pressure) up to 5000 g compression. We showed previously in tests with 4.8F, 6F, and 7F stents that deformation and compression alone are not generally sufficient to lead to stent failure under EUO. ⁷

Based on the two complete sets of experiments, monitoring four replicates of stented ureters under deformation and compression and two replicates of the control (unperturbed) stented ureters, the average time for stent failure in the 4.8F and 6F stents was 44 hours (range 31–59 hours) and 66 hours (range 24–92 hours), respectively, as shown in Table 1. The 7F ureteral stent failed in two of the repetitions after an average time of 75 hours and continued to drain in the other two repetitions with a mild rise in renal unit pressure throughout the experiment. The 8F ureteral stent showed no change in renal unit pressure in any of the repetitions. Significantly, none of the control stents with no deformation or compression (4.8F, 6F, 7F, and 8F) exhibited any change in renal pressure in any of the replicates. It is noted that throughout the experiments, small rises (as much as 1–1.5 cm)—and then falls—were observed in some of the piezometers, evidently as pressure builds up and colloids are then released or rearranged in the stented ureter system.

Discussion

The fact is that polymeric ureteral stents often fail under EUO. ² While it may be intuitive to attribute stent failure to deformation of the ureter and external pressure, which lead to occlusion of the stent lumen, it appears that reality is more complex. We showed previously ⁷ that deformation and compression alone do not generally cause stent failure, at least over periods of days. Other authors ¹ suggested that colloids or debris play a role in obstructing stents and thus stent failure. In this experiment, based on the control stented ureter system, we find that colloids alone do not cause stent failure over the same duration. Rather, it is the combination of external pressure, deformation, and colloid concentration that can lead to stent failure. For a stented ureter under EUO, the main path for urine to flow down into the bladder, in the vicinity of the EUO, is through the ureteral stent lumen. We find that the 4.8F stents fail consistently, as do the 6F stents. The 7F stent also shows a tendency to failure, while the 8F stent is not prone to failure (at least relative to the time scales for failure of the other stents). Variability in time to failure is evident, even among stents with the same size: this behavior is reasonable given the random nature of colloid inflow, aggregation, and trapping within the stent lumen and within the ureter–stent annular lumen, as well as the possible impact of the stent side holes and their potential blockage. These findings, which support the use of large lumen stents in EUO, are consistent with opinions of other authors ^1,15 who concluded that the use of stents with maximal diameters is preferable as they are more resistant to (or less likely to suffer from) obstruction.

The advantage of larger luminal stents under EUO may be related to several possible explanations, but largely to the fact that flow is facilitated through stents with a larger inner diameter. Noting that urine can flow along (often interconnected) pathways through the stent (intraluminal) and through the ureteral lumen (between the stent and the ureter wall, extraluminal), for example, Brewer et al. ¹⁵ measured intraluminal, extraluminal, and total flow rates of urine in stented ureters of minipigs through in vivo experiments. These authors noted that larger luminal stents had higher intraluminal and total flow rates compared with narrower stents. Additionally, in this context, the authors emphasized the significance of the internal stent diameter rather than its external diameter. This fact should be emphasized given reported differences of ureteral stent wall thicknesses among different manufacturers, and even among various sizes of stents by the same manufacturer, which lead to stents of the same (e.g., 6F) size having different internal diameters. ^7,16

Another advantage of large luminal ureteral stents under EUO derives from the influence of external pressure over the stented ureter. Because the internal diameter improves luminal flow, it is important for the stent to be resistant to outer and radial pressure to prevent partial occlusion of the stent. Hendlin et al. ¹⁷ noted that larger luminal stents are less resistant to radial compression that can lead to stent occlusion. However, their model used a two-point opposing pressure rather than areal pressure, which was placed directly on the stent rather on a stented ureter. Davis et al., ¹⁶ on the other hand, showed a 6F ureteral stent to be more resistant to radial pressure than a 4.8F stent, underlining the resistance of larger ureteral stents to radial compression; the wall thickness of the 4.8F stent, too, was smaller than that of the 6F and 7F stents.

In our experiments, visual examination of the obstructed stented ureter units indicated that colloids accumulated both within the stent (insertion of a guidewire released colloidal aggregates; measuring the length of the inserted guidewire confirmed the approximate location of the aggregates) and in the ureter–stent lumen, at and proximal to the region of compression as well as further proximal to it. In addition, larger colloids were seen to accumulate near the region connecting the renal unit to the stented ureter (the simulated ureteropelvic junction), particularly for the larger (7F, 8F, and in some cases, the 6F) stents. A possible explanation for this finding is that the lumen between the stent and the ureter is relatively narrow so that some larger colloids (and colloid aggregates) can accumulate in this region, while others can travel through the stent. In contrast, the wider lumen between the ureter and the 4.8F stent enables the passage of larger colloids. When considering colloids (and colloid aggregates), it should also be noted that hole diameters along the stent walls vary in size, being largest for the 7F and 8F stents, smaller for the 6F stent, and even smaller for the 4.8F stent. A combined (in vitro) experimental and computational fluid dynamics study by Mosayyebi et al. ¹⁸ demonstrated similar particle accumulation behavior in a stented ureter around inactive stent holes and ureteral cavities formed by occlusions. These obstructed regions, with low wall shear stress, facilitate encrustation, particularly at lower flow rates. Indeed, we believe that stent encrustation and incrustation may resemble the process in which debris and colloids obstruct the stent–ureter lumen.

Finally, we note that results obtained here for colloid accumulation, in both the stent and the stent–ureter lumen, are supported by the fluid dynamics theory. First, fluid flow in a curved annulus having a local constriction at the outer wall—such as in the case of a curved and deformed stented ureter subjected to EUO—is prone to significant variations in the pressure gradient and frictional resistance, which lead to a highly nonuniform flow pattern. ¹⁹ Second, and especially for strong laminar flow such as in our system, ⁷ quantitative analysis ^20,21 of colloid suspensions in tubular flow shows that colloids can accumulate particularly in regions where curvature, deformation, and compression alter the cylindrical cross section of a tube and/or annulus (such as in the vicinity of an EUO in a stented ureter).

There are several limitations to our study. The latex tubing simulating a ureter has physical characteristics that are different from real ureteral walls (which vary among patients and in response to different treatments) and the lack of (even minimal) peristaltic motion may have some effect on the results. Moreover, dynamic ureteral responses caused by indwelling stents and EUO will likely further affect the flow dynamics over time, such as reflux or retrograde pressure transmission through and/or around the stent. Moreover, the results here are a function of the type and concentration of colloid material and the use of DDW containing no other salts, enzymes, and organic materials. As such, stent mineralization, various colloid aggregation properties, and biological activity remain unaccounted for. Clearly, the occurrence of blockage and the actual time to blockage (and variability among replicate experiments) are also affected by colloid concentration. Another limitation is our use of single polymer stents, while metal and tandem (polymer) ureteral stents are currently reported ^22,23 to treat the EUO with encouraging success rates. On the other hand, larger diameter stents and tandem stents might be less tolerable for patients. Notwithstanding the above, we note that to the best of our knowledge, this is the first study to systematically measure effects of colloidal fluid flow in stented ureter systems, both under and without EUO, while also accounting for the relative impact on stents of different sizes.

Conclusions

The phenomenon of stent failure under EUO is commonly attributed to extrinsic pressure placed on the ureter and stent. We suggest that the presence of colloids in urine may play a critical synergetic role in stent failure. We evaluated the efficacy of different ureteral stent diameters under EUO in the presence of colloidal material in the fluid, demonstrating that large-diameter stents are more effective in ureteral drainage under EUO. We conclude that colloidal fluid may play a critical role in stent failure under EUO. These experiments may assist in selection of the most effective stent for drainage.

Future experiments using different colloid compositions and concentrations, and/or employing urine, as well as examining other types of ureteral stents (e.g., metal and [polymer] tandem) to further understand and confirm factors that control stent failure under EUO remain to be undertaken.