DOI of original article:10.1016/j.eururo.2005.12.008
M.M. van Dijk *, C.A. Mochtar, H. Wijkstra, M.P. Laguna, J.J.M.C.H. de la Rosette
Department of Urology, Academic Medical Center, University of Amsterdam, the Netherlands

Abstract

Objectives: To assess the efficacy, safety, and durability of the bellshaped nitinol prostatic stent in the treatment of moderate to severe lower urinary tract symptoms caused by benign prostatic enlargement in otherwise healthy patients.

Methods: Stents were inserted in an outpatient setting under local anaesthesia. Assessments included maximum urinary flow (Qmax), postvoid residual (PVR) urine volume, International Prostate Symptom Score (IPSS), including quality of life (QoL) item, at baseline and follow-up visits.

Results: 108 men were enrolled in the trial. Stents were successfully inserted in 97% of the patients. Spontaneous voiding was achieved in all patients. After one month Qmax (+3.7 ml/s), PVR (
99 ml), IPSS (
12) and QoL (
1.7) all showed statistically significant improvements compared to baseline. Substantial improvements, however, were maintained for only one to two months. The main complications were haematuria (19%), urge incontinence (22%), and migration (15%). The median indwelling time was 105 days. The main reason for removal of stents was worsening of symptoms, which might be attributable to the tilting of stents within the prostatic urethra, found upon removal.

Conclusions: Insertion of the bell-shaped nitinol prostatic stent temporarily improves voiding parameters and symptom scores. Because of the limited durability, however, the bell-shaped prostatic stent is not suitable for clinical practice.

1. Introduction

Prostatic stents aim at rapid alleviation of lower urinary tract symptoms (LUTS) in patients with benign prostatic enlargement (BPE) by relieving obstruction. In the literature, prostatic stents have been classified into two categories: permanent and temporary. The major characteristic of prostatic stents meant for permanent use is that they allow tissue ingrowth, which results in the stent being embedded in the urethral wall. In contrast, temporary stents are made of non-absorbable material which prevents epithelialization, thereby facilitating easy removal. They were primarily designed for short-term application, ranging from a few weeks to several months. However, longer term use with a follow-up period of eight years has also been described [1].

One example of a stent designed for temporary use is the spiral stent. Early spiral stents [2?9] were non-expandable coiled wires made of stainless steel; spiral stents of the second generation [1,10?12] are made of an alloy of nickel and titanium (nitinol), which is either self- or thermoexpandable. In a previous report [12], we described our experience with one of the nitinol spiral stents with a thermal shape memory, the hourglassshaped prostatic stent, in 35 patients with LUTS caused by BPE. Because of a high migration rate, this stent appeared not to be suitable for clinical practice. An explanation for this was sought in the design of the stent. It had an increasing diameter towards both ends and the proximal wide end might have caused it to be pulled into the bladder, instead of anchoring it in the prostatic fossa. Therefore, the successor of the hourglassshaped stent was designed with an increasing diameter towards the distal end only (bell-shaped), with the purpose of fixing it at the apex of the prostatic fossa.

Because of significant complications such as encrustation, infection, migration, and chronic pain, the current guidelines on benign prostatic hyperplasia recommend the use of prostatic stents in patients with high operating risk only [13]. Since the bell-shaped prostatic stent was especially designed to prevent such complications, this study was performed in a group of patients without significant co-morbidities.

A prospective study was conducted to determine the efficacy, safety, and durability of the bell-shaped nitinol prostatic stent as a treatment option for moderate to severe LUTS caused by BPE in otherwise healthy patients.

2. Materials and methods

2.1. Patients

The study was conducted in accordance with the regulations of the local ethical committee. A written informed consent was given by all patients before any study-related proceedings were conducted. Men with moderate to severe LUTS (defined as an International Prostate Symptom Score [IPSS] >7) caused by BPE were included in the study. Exclusion criteria were a history of urinary tract malignancies, previous pelvic irradiation or surgery, prior medical, minimally invasive, or surgical treatment for LUTS caused by BPE, urolithiasis, insufficient detrusor contractions (measured by urodynamic investigation), and urinary tract infections.

The pre-treatment evaluation included transrectal ultrasonography to determine prostate volume, uroflowmetry to measure maximum urinary flow (Qmax), ultrasonography of the bladder to assess postvoid residual (PVR) urine volume and the IPSS questionnaire, including the Quality of Life (QoL) item. Follow-up evaluations of voiding parameters, symptom scores, and complications were performed at one week and one, three, six, 12, 18, 24, and 30 months after stent insertion.

2.2. Stents

The stent was made of nitinol with a temperature-based memory for the shape, making the stent pliable when cooled (10?15 8C), returning to its original shape when heated (38? 42 8C). The stent was a circular coil with a larger diameter at the distal end of the stent (Fig. 1) and was available in six different lengths, ranging from 3.5 to 6.0 cm. The stent length was chosen to be 0.5 cm longer than the prostatic urethra, which was measured cystoscopically using a calibration catheter from the bladder neck to the verumontanum. The diameter of all stent sizes was 1.5 cm at the distal and 0.8 cm at the proximal end when expanded.

2.3. Insertion

The stent was pre-mounted in a delivery system consisting of three co-axially placed plastic sheaths (Fig. 1). The stent was placed between the inner and the middle sheath and attached to two wire restrainers which prevented the stent from deploying until properly positioned. The inside diameter of the system was slightly larger than 12 Fr to accommodate a 12 Fr rigid cystoscope. The procedure took place in an outpatient setting under antibiotic prophylaxis and local anaesthesia. The delivery system and cystoscope were advanced into the urethra. At approximately 0.5 cm beyond the bladder neck, the stent was released by unfastening the restraining wires while irrigating with heated solution, which allowed the stent to fully expand. After the procedure, urethroscopy was performed to verify correct placement. At the follow-up visits, the position of the stent was checked with abdominal sonography of the bladder. To evaluate the intensity of pain during the procedure, a visual analogue scale (VAS) ranging from 0 (no pain) to 10 (the worst pain imaginable) was administered to the patient.

2.4. Removal

Stents were removed in case of migration, other severe complications, or when symptoms worsened considerably. Removal was performed under local anaesthesia and antibiotic prophylaxis in the outpatient department using a rigid 08 cystoscope. The stent was irrigated with cooled solution which caused it to become pliable. It was pushed into the bladder, after which it was grasped with a forceps and pulled outside through the sheath of the cystoscope. All insertions and removals were performed by the same urologist. The ease of both procedures was scored from 1 (very easy) to 5 (very difficult) by the urologist performing the procedure.

2.5. Statistics

The significance of longitudinal changes in voiding parameters and symptom scores was assessed by repeated measures analysis using a linear mixed model, in which missing data and patient dependency are taken into account. Kaplan-Meier analysis was used to assess the survival of the stent. A multivariable Cox regression model was used to analyse differences in risk of stent removal by increasing prostate volume, age, and stent size. In these analyses, the endpoint was defined as removal of the stent; patients in whom stents were not placed were not taken into account. Spearman?s test was used to assess the correlation between the difficulty of stent removal and the number of days of removed stents in situ. Chi-squared test was employed to determine the relation between urge incontinence and migration. All inferential statistical tests were significant at p < 0.05. Statistical analyses were executed with the statistical software SPSS for Windows, version 11.5.1, SPSS Inc. Chicago, IL, USA.

3. Results

3.1. Patients Between July and November 2002, 108 patients underwent placement of the bell-shaped prostatic stent. Table 1 presents an overview of mean patient baseline characteristics. At baseline, two patients had an indwelling urinary catheter because of urinary retention. Throughout the course of the study, two patients were lost to follow-up.

3.2. Insertion Stents were successfully inserted in 97% of the cases. In three patients (3%) stent placement was not possible because of a steep bladder neck (two) and bad deployment of the delivery system (one). In 11 patients, two placement attempts were needed to accomplish correct placement. Cystoscopy after the procedure showed that all stents had properly expanded. The ease of the insertion was graded with a mean (SD) score of 2.2 (1.0) by the urologist performing the procedure. The mean (SD) pain intensity score on the VAS administered directly after the procedure was 3.7 (2.3). All patients experienced transient haematuria directly after the placement. In most patients, the haematuria was only minimal; in five patients, however, a clot retention occurred within the first week.

3.3. Voiding function Spontaneous voiding was achieved in all patients directly after insertion of the stent. Fig. 2 shows the



results of voiding parameters at baseline and at each follow-up visit. At one week and one month after insertion, Qmax statistically significantly improved compared to baseline (+5.5 and +3.7 ml/ s respectively; p < 0.001). At the three months visit, the improvement in Qmax did not reach statistical significance (+0.5 ml/s; p = 0.518). Thereafter, except for the visit at 24 months, mean Qmax showed a varying decline compared to baseline; these differences were not statistically significant. PVR also immediately significantly improved compared to baseline (
115 ml; p < 0.001). Although the differences became less obvious over time, mean PVR remained below baseline values throughout the entire follow-up period. The only visit at which these improvements were not statistically signifi- cant was at 24 months (
41 ml; p = 0.054).

3.4. Symptom scores

The courses of mean IPSS and QoL scores throughout the entire follow-up period are shown in Fig. 3. One week after placement, IPSS improved only slightly compared to baseline (
1; p = 0.157). After onemonth, however, a substantial and statistically significant improvement in IPSS (
12; p < 0.001)was

observed. Thereafter, improvements in symptom scores became less obvious, although still statistically significant until 24months (
6; p = 0.001). QoL did improve significantly (
0.8; p < 0.001) right away compared to baseline. It took one month to reach the maximumimprovement (
1.7; p < 0.001), however. Decreases in QoL score remained statistically significant throughout the entire course of the study.

3.5. Complications

Twenty-four (22%) patients reported intermittent episodes of urge incontinence; one of these patients had mentioned incontinence at baseline as well. Seventy-five percent of these episodes were observed at the last visit before removal. In all cases, the incontinence was mild, and none of the patients needed protective pads. The incontinence was not related to migration ( p = 0.13). From a follow-up of one month onwards, transient haematuria was observed by 21 (19%) patients. In seven patients, the haematuria seemed to be related to physical exercise such as cycling and jogging. In one patient, in which the haematuria had started after a fall, a clot retention occurred, which was resolved by transurethral catheterisation by the general practitioner. Retrograde ejaculation was reported by 18 (17%) patients and another seven (6%) patients complained of painful ejaculation. Only one of these patients was known with retrograde ejaculation at baseline. Urinary tract infections were experienced by seven (6%) patients.

3.6. Survival analysis

The median time to removal of the stent was 105 days. The mean (SD) indwelling time was 301 (352) days. Kaplan-Meier survival analysis shows that at one month after insertion of the stent, 87% of the stents were still in situ. At three, six, 12, 18, 24, and 30 months follow-up, the survival rate was 54%, 37%, 32%, 26%, 22%, and 18%, respectively. The curve presenting the Kaplan-Meier analysis is shown in Fig. 3. There was no difference in risk for stent removal over time with increasing prostate volume (p = 0.81), age ( p = 0.31), or stent size ( p = 0.56).

3.7. Removal

The main motive for removal of the stents was worsening of symptoms (75%). Other reasons were migration (14%), clot retention (6%), haematuria (3%), and acute urinary retention (2%). Removal took place in the outpatient department under local anaesthesia in 94% of the patients. In two patients with severe co-morbidities, the stents were removed in the operating room in order to be able to monitor them more intensively. In another four patients, the procedure was too painful under local anaesthesia, whereupon removal was performed under spinal (two) or general anaesthesia (two).

Upon removal, 13 (15%) of the stents appeared to have migrated into the bladder and 17 (20%) had partially migrated towards the bladder. The other stents had remained their position in the prostatic urethra. However, these stents had tilted within the prostatic urethra, with the distal end of the stent angled dorsally.

Bullous epithelial hyperplasia was seen in two patients (2%). Mild encrustation was found on 13 (15%) of the removed stents. Haematuria occurred in 66 (76%) of the patients after the procedure and 30 (35%) of the patients were given a catheter to prevent urinary retention.

The urologist performing the procedure rated the level of difficulty of the removal with a mean (SD) of 2.9 (1.4). There was no significant relationship between the difficulty of stent removal and the number of days of the removed stents in situ ( p = 0.364). The removal was significantly more difficult than the insertion ( p < 0.001; Wilcoxon signed ranks test). 4. Discussion Since the first use of prostatic stents, described by Fabian in 1980 [9], a variety of indications has been a subject of study. Most studies have assessed the technique of stenting the prostatic urethra in patients with high operating risks. Another indication is the use after various thermotherapy treatments to prevent postoperative urinary retention caused by oedema [14,15]. Some studies, including our former study with the hourglass-shaped stent, investigated prostatic stents as a treatment option in patients without significant co-morbidities [12,16?18]. Because the bell-shaped stent was specifically designed to solve the problems encountered with the hourglass-shaped stent, the present study was conducted in a comparable group of otherwise healthy patients with LUTS caused by BPE. The ideal prostatic stent should be easy to insert and remove under local anaesthesia. Since the ease of the insertion and removal of stents in this study was scored by only one urologist experienced in this procedure, the results of these scores should be construed with care. Insertion of the bell-shaped stent was easy. It was performed in an ambulant setting in all patients, who experienced only mild to moderate pain during the procedure. Although the removal was more difficult than the insertion, it needed to be performed in the operating theatre in only 6% of the patients. These results are comparable to the former study with the hourglass-shaped nitinol stent [12].

Placement of the stent resulted in immediate spontaneous voiding in all patients with significant improvements in voiding parameters and symptom scores. The statistically significant improvement in IPSS was not seen in the first week after placement of the stent. The maximum improvement in QoL was also not achieved until one month after placement. These results are not compatible with the results of Qmax and PVR, which did show significant improvements at one week after insertion. An elucidation for this might be that the stent caused irritation of the trigone, which can also been seen the first days after an indwelling catheter is inserted.

The durability of the bell-shaped prostatic stent was limited; whereas one month after insertion 87% of the stents were still in situ, after three months, the survival rate had declined to 56%. The main reason for removal was worsening of symptoms. In our opinion, the phenomenon of tilting of stents within the prostatic urethra could be a contributory factor with respect to the worsening of symptoms and decrease in voiding function after one to two months. The tilting might be attributable to the fact that the stents are not tailored to the variety of shapes of the prostatic urethra. The prostatic urethra is frequently curved (concave anteriorly) to varying degrees, whereas the bell-shaped stent is completely straight. In addition, the prostatic urethra does not always conform to the cylindrical shape of these stents [19].

The main complications encountered in this trial were haematuria, urge incontinence, and migration. The haematuria directly after the insertion procedure was probably the result of small lesions of the urethra caused by delivery system manipulation. An explanation for the transient haematuria occurring during the course of the trial might be that physical activity caused friction of the stent within the prostatic urethra, leading to damage of the urethral lining. In studies on other spiral stents of the second generation, haematuria occurred in 3?23% of the patients [1,11].

The urge incontinence was mostly experienced at the last visit before removal of the stent. It was probably one of the contributing aspects of the worsening of symptoms, which was the reason for stent removal in most patients. In papers on other types of temporary prostatic stents, urge incontinence was described in 0?23% of the patients [1,10,11,16,20?22]. Displacement of stents, which could sometimes be resolved by cystoscopical repositioning of the stent, was mentioned as a possible reason for this [10]. In the current study, incontinence did not occur more often in patients whose stent had migrated; it might have been caused by foreign body irritation of the external sphincter.

The migration rate into the bladder of the bellshaped stent (15%) was considerably lower than that of the hourglass-shaped stent (93%), although it was still not negligible. Since the first description of prostatic stents by Fabian in 1980 [9], migration has been an important impediment to widespread clinical application of prostatic stents. Migration was particularly a problem in the non-expandable first-generation spiral stents (10?38%) [2?8], but reports on other temporary stents showed varying high migration rates [14,16,20,21,23] as well. The Memokath prostatic stent, which is a thermoexpandable spiral stent with a comparable shape to the bell-shaped stent, migrated less often (0?13%) [1,11].

The limited durability and the complications encountered in this study make the bell-shaped stent unattractive for clinical application. To move towards a more durable use, modifications in stent design are required.

5. Conclusions

The bell-shaped nitinol prostatic stent is easy to insert and remove under local anaesthesia. It immediately improves voiding function and signifi- cantly alleviates symptoms. Substantial improvements, however, are maintained for only one to two months, which might be attributable to the tilting of stents within the prostatic urethra. Therefore, the bell-shaped prostatic stent in its current design is not suitable for clinical practice. To minimize displacement of stents and improve the durability of this treatment, advanced adjustments in stent design are indispensable.

Acknowledgments

The bell-shaped nitinol prostatic stents were provided free of charge by Endocare, Inc. The authors would like to thank A.S. Glas, M.D., Ph.D. for her contribution to the statistical analysis. References
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Source: European Urology February 2006