Tissue hyperplasia: influence of a paclitaxel-eluting covered stent--preliminary study in a canine urethral model

PURPOSE: To evaluate a paclitaxel-eluting covered stent in reduction of tissue hyperplasia after stent placement in a canine urethral model. MATERIALS AND METHODS: Procedures were performed in accordance with the National Institutes of Health guidelines for humane handling of animals; approval of the committee of animal research was obtained. Twenty paclitaxel-eluting polyurethane-covered stents (drug stents) and 20 polyurethane-covered stents (control stents) were placed alternately between the proximal and distal urethra in 20 male dogs. The dose of paclitaxel was approximately 1800 mug in each drug stent but absent in each control stent. Dogs were sacrificed either 4 (n = 10) or 8 (n = 10) weeks after stent placement. The percentage diameter of stenosis was assessed with follow-up retrograde urethrography and histologic findings obtained after sacrifice and compared between drug stents and control stents and between the proximal and the distal urethra. RESULTS: Two drug stents partially migrated during retrograde urethrography immediately after stent placement; they were removed and replaced with a second stent during the same procedure. There was a strong tendency toward a lower percentage diameter of stenosis and numeric mean values of the four histologic findings, which indicates less formation of tissue hyperplasia in the proximal urethra than in the distal urethra. In particular, thickness of the papillary projection denoting the entire thickness of hyperplastic reaction was significantly less in drug stents than in control stents in the proximal urethra in the 8-week group (P = .016, Mann-Whitney U test). CONCLUSION: Local delivery of paclitaxel via covered stents has the potential to reduce tissue hyperplasia secondary to stent placement in a canine urethral model. With stent placement, there are distinct differences of tissue hyperplasia between the proximal and distal urethra.     

Flexible tantalum stents: Effects in the stenotic canine urethra

Purpose Evaluate the effects of flexible tantalum stents (Strecker) implanted into stenotic canine urethras.Methods Eight conditioned, adult, German shepherd dogs, weighing 30–40 kg, were used. Strictures were created surgically in the bulbar urethra just proximal to the os penis. Two months postsurgery, strictures were documented radiographically and then balloon dilated. Following dilatation, a single Strecker stent was placed across the stricture. Stents were 7 mm in expanded diameter and either 2 or 4 cm in length. Retrograde urethrography was performed immediately after stent placement and then biweekly for up to 12 months. Two dogs were sacrificed at 2, 4, 6, and 12 months post-stenting, and necropsy was performed. The urethra was excised, fixed, and examined by scanning electron and light microscopy.Results Clinical success was achieved without complications in all animals. Hyperplasia of the urothelium was noted 4–6 weeks after stent placement and was most pronounced at 4–6 months. Mucosal folds were found between the stent struts. Restenosis occurred at the distal end of the stent in one dog. Histological alterations were noted in the deeper layers of the urethral wall.Conclusion Strecker stents were well tolerated in all animals and seem useful for the treatment of urethral strictures.Presented at CIRSE Annual Meeting and Postgraduate Course, Budapest, June 20–24, 1993     

Prostatic urethra dilatation with the Gianturco self-expanding metallic stent: a feasibility study in cadaver specimens and dogs.

In an effort to develop a transcatheter technique for dilatation of the prostatic urethra without the use of balloons, the feasibility of using Gianturco self-expanding stents was evaluated. Initially, eight human cadaveric prostatic urethras were stented to evaluate the ability of the stent to dilate the lumen. In all cases, the device attained its unconstrained diameter immediately on placement. Subsequently, stents were placed in the prostatic urethra of 12 dogs and followed up for 1 month (four dogs), 3 months (one dog), and 6 months (seven dogs). Five bare straight-end prostheses, one nylon-covered straight-end device, and six flared-end stents were used. Three of the bare straight-end stents migrated during the follow-up, whereas the nylon-covered and flared-end stents did not. Stent diameters greater than 1.3 times the urethral diameter caused moderate to marked edema and inflammation. After 6 months, white deposits were found on the solder points, presumably from electrolysis. Our experience suggests that placement of Gianturco self-expanding stents may be a useful method of dilating and maintaining the luminal diameter of the prostatic urethra, although care must be taken to select the proper stent size.     

Is a flared stent effective for decreasing stent migration in canine prostatic urethra?

Background: Prostatic urethral stents are effective in relieving obstructions caused by benign prostatic hyperplasia (BPH). However, migration of these stents occurs frequently.

Purpose: To evaluate the efficacy of a flared stent for decreasing the migration rate in comparison with a straight stent in a canine prostatic urethral model.

Material and Methods: The flared stent (15 mm in diameter and 20 mm in length) was flared up to 19 mm at both ends to prevent migration. A straight stent with the same size was straight without flaring. Both stents were made of a nitinol wire filament and covered with an expanded polytetrafluoroethylene (ePTFE) membrane. The flared stent was inserted in the prostatic urethra of 10 dogs (group 1) and the straight stent in the prostatic urethra of 12 dogs (group 2). Follow-up retrograde urethrography (RUG) was performed 1, 4, and 8 weeks after stent placement. Fisher's exact test was used to compare the migration rate between the two groups. When stent migration occurred during the follow-up period, the same type of stent was inserted again.

Results: Three of 10 (30.0%) flared stents migrated into the urinary bladder between 1 week and 4 weeks after placement. Seven of 12 (58.3%) straight stents migrated into the urinary bladder 1 (n = 3), 4 (n = 1), and 8 (n = 3) weeks following placement. The flared stent group showed lower migration rate than the straight stent group, but the migration rate did not reach statistical significance (P = 0.231). After the second stent placement, one of three (33.3%) flared stents migrated again after 4 weeks and two of seven straight stents (28.6%) after 1 week.

Conclusion: Although the migration rate was not statistically significant, the flaring of the stent seemed to reduce the migration rate in comparison with straight stents in a canine prostatic urethral model. However, the migration rate of the flared stent was still high, and further developments are required to decrease migration rate.     

X线监视下经尿道植入支架治疗高龄前列腺增生症

目的评价植入网状记忆合金支架治疗高龄前列腺增生症尿道狭窄的临床效果和可行性。方法47例患者,年龄72~93岁,平均78.3岁,排尿困难7~21年。1%利多卡因尿道黏膜麻醉,DSA引导下经尿道将支架放置在前列腺尿道最狭窄处。结果47例患者均一次治疗成功(100%),其中43例支架植入后立即自行排尿,排尿通畅。本组无1例出现尿道再狭窄和结石等情况,排尿通畅率100%。结论记忆合金网状支架治疗前列腺增生引起的排尿困难临床疗效显著,值得临床推广应用。     

尿道内支架置入术初步实验研究

目的：主要了解尿道粘膜对内支架置入后的反应。材料与方法：雄性犬５条。球囊扩张式钽丝支架（Ｓｔｒｅｃｋｅｒｓｔｅｎｔ），内支架扩张后内径６ｍｍ。先行逆行尿道造影后，支架置入前列腺部位尿道内，术后３天、２周和１个月造影复查，取病理检查。结果：造影复查显示尿道通畅，有１例内支架移位。病理巨检见支架与尿道结合紧密，支架网眼内粘膜增生，镜检示粘膜上皮细胞增生，结缔组织内有炎性细胞浸润及小血管增生，电镜下钽丝表面光滑。结论：粘膜上皮对该内支架无明显炎性反应，适用于前列腺成形术。     

Renal cyst pseudoenhancement: evaluation with an anthropomorphic body CT phantom

PURPOSE: To evaluate the feasibility of using a retrievable urethral stent and to evaluate whether granulation tissue resolves after stent removal in a canine urethra. MATERIALS AND METHODS: Polyurethane-covered retrievable 0.10-mm-thick (n = 11) or 0.15-mm-thick (n = 10) nitinol wire stents were placed in the urethras of 20 dogs. In one dog, a second stent was placed in the urethra because of complete migration of the first stent into the urinary bladder. The stents were removed with retrieval hook wires 4 weeks (n = 10) and 8 weeks (n = 10) after placement. Fourteen dogs were sacrificed just after stent removal, and the other six dogs were sacrificed 2 weeks after stent removal. Information concerning procedure success, stent migration, and tissue response was obtained. RESULTS: Stent placement was technically successful in all dogs. Follow-up urethrograms showed partial (n = 4) or complete (n = 1) stent migration. Stent removal failed in two dogs due to partial or complete migration. Granulation tissue was observed at both ends of the stent in 17 dogs. Urethrograms and urethral specimens obtained 2 weeks after stent removal showed diminished granulation tissue and decreased thickness of the papillary projections of the epithelium compared with results obtained immediately after stent removal. CONCLUSION: Although some design modifications are necessary to reduce current complications, the polyurethane-covered retrievable nitinol stent seems feasible for use in the urethra. Stent-induced granulation tissue formation improved after stent removal.     

Stricture disease: radiology of urethral stents

Self-expanding metal stents are emerging as an effective alternative treatment in the management of urethral obstruction. The radiologic studies of 33 men with anterior urethral strictures (subprostatic, n = 11; bulbar, n = 22) that had recurred despite repeated optical urethrotomy and dilation were reported. In all patients, the stricture was successfully treated with stent insertion. Urethrography performed 1 month later in 19 patients showed an irregular intrastent lumen of varying degrees due to a hyperplastic urothelial reaction confirmed at endoscopy the same day. Available follow-up urethrograms in seven patients at 3 months showed that the hyperplasia was settling, and by 6 months, the intrastent lumen was smooth and of good caliber. Urethrography revealed postoperative structures in 14 patients. Strictures seen at 1 month (n = 6) were due to initial stent misplacement and were treated with the insertion of a second stent. Strictures seen 3 months after insertion (n = 4) occurred within the stent lumen and were considered to be significant at endoscopy in only one patient. Strictures that developed 6-12 months after stent insertion (n = 4) were not within the stent and were considered to represent genuine new strictures.     

Experimental study of the intraurethral placement of expandable metallic stents

Various types of Gianturco expandable metallic stents were implanted into the urethra of four dogs in order to evaluate the suitable expandability of the stents in urethra and also to determine the effect of the stents on the urethral wall. The stent of 1.5 cm in length and constructed of 0.010 inch round stainless steel wire with twelve zigzag bends showed the suitable expandability on the canine urethra compared to the other stents. The urethra remained patent and the inflammatory changes on the urethral wall were moderately noted. No hematuria or calcifications around the stents were noted in any dogs. The experimental data showed a potential clinical application.     

Temporary placement of covered retrievable expandable nitinol stents with barbs in high-risk surgical patients with benign prostatic hyperplasia: work in progress

Purpose

To report the use of a newly constructed, covered, retrievable, expandable nitinol stent with barbs to overcome the problem of stent migration associated with conventional covered prostatic expandable stents and to evaluate prospectively the technical feasibility and clinical effectiveness of the stents in patients with benign prostatic hyperplasia (BPH).

Materials and Methods

A covered retrievable expandable nitinol stent with four barbs was placed with use of an 18-F stent delivery system in seven consecutive patients with symptomatic BPH who had high operative risks. Age range of patients was 62–83 years (mean 74 years). In cases in which the stent migrated, it was replaced with a stent with eight barbs. The stents were routinely removed 4 months after placement using a 21-F stent removal set.

Results

Stent placement was technically successful and well tolerated in six of the seven patients. The remaining patient needed a second stent placement after removal of the first stent. The stent with four barbs migrated into the urinary bladder in four patients (57%); three of these patients received a second stent with eight barbs with good results, and the fourth patient did not need further treatment because his symptoms improved. Routine removal of the stent 4 months after placement was performed in three of the seven patients with good results.

Conclusions

Retrievable stents with eight barbs seem to overcome the problem of stent migration associated with conventional prostatic expandable stents. Preliminary results suggest that stents with barbs are both feasible and effective in patients with BPH.     

Polydioxanone Biodegradable Stent Placement in a Canine Urethral Model: Analysis of Inflammatory Reaction and Biodegradation

PurposeTo investigate the inflammatory reaction and perform quantitative analysis of biodegradation after placement of a polydioxanone (PDO) biodegradable stent in a canine urethral model.Materials and MethodsPDO biodegradable stents were placed in the proximal and distal urethra of nine male mongrel dogs. The dogs were euthanized 4 weeks (group A; n = 3), 8 weeks (group B; n = 3), or 12 weeks (group C; n = 3) after stent placement. The luminal diameter of the stent-implanted urethra was assessed by follow-up retrograde urethrography, and histologic findings were obtained after the dogs were killed. Stents were removed after euthanasia, and their surface morphology and molecular weight were evaluated. Hematologic examination was performed to evaluate inflammatory reaction.ResultsStent placement was technically successful in all dogs. The average luminal diameter gradually decreased. The average number of epithelial layers (2.93 vs 4.42; P < .001), the average thickness of papillary projection (0.80 mm vs 1.28 mm; P < .001), and the average thickness of submucosal fibrosis (0.34 mm vs 0.49 mm ; P < .001) were significantly increased in group B versus group A. There were no significant differences between group B and group C. The average inflammatory cell infiltration did not differ significantly in the three groups. Molecular weight losses were 54% in group A and 84% in group B. In group C, PDO stents were completely decomposed.ConclusionsAn experimental study in a canine urethral model has demonstrated acceptable inflammatory reaction with gradually increasing granulation tissue but no luminal obstruction within 12 weeks.     

Imaging of male urethra

The male urethral imaging and pathology is not widespread in the radiology literature because this part of the urinary tract is easily studied by urologists with clinical or endoscopic examinations. Ultrasonography and MR imaging are increasingly being used in association with voiding cystourethrography and retrograde urethrography. The posterior urethra is being studied with voiding cystourethrography or voiding sonography which allows the detection of bladder neck pathology, post-surgical stenosis, and neoplasms. The functional aspects of the bladder neck and posterior urethra can be monitored continuously in patients with neuromuscular dysfunction of the bladder. The anterior urethral anatomy and pathology is commonly explored by retrograde urethrography, but recently sonourethrography and MR imaging have been proposed, distending the lumen with simple saline solution instead of iodinated contrast media. They are being used to study the urethral mucosa and the periurethral spongy tissue which can be involved in the urethral pathologies such as strictures, diverticula, trauma, and tumors. Imaging has an important role to play in the study of the diseases of the male urethra since it can detect pathology not visible on urethroscopy. The new imaging techniques in this area, such as sonography and MR, can provide adjunct information that cannot be obtained with other modalities.     

Reduction of tissue hyperplasia with a rhenium-188 mercaptoacetyltriglycine-3-filled balloon: preliminary study in a canine urethral model

PURPOSE: To evaluate the efficacy of beta-radiation therapy with rhenium-188 mercaptoacetyltriglycine-3 (MAG(3))-filled balloons to reduce tissue hyperplasia secondary to stent placement in 18 canine urethras. MATERIALS AND METHODS: Eight dogs were treated with 188-Re MAG(3)-filled balloon dilation immediately after stent placement and were killed 4 weeks later (group I, n = 4) or 8 weeks later (group II, n = 4). Five dogs were treated with 188-Re MAG(3)-filled balloon dilation 2 weeks after stent placement and were killed 4 weeks after stent placement (group III). The remaining five dogs were treated with conventional balloon dilation immediately after stent placement and were killed 4 weeks later; these animals formed the control group (group IV). Retrograde urethrography (RUG) was performed during follow-up and three histologic parameters were investigated: the number of epithelial layers, papillary projection thickness, and degree of submucosal inflammatory cell infiltration. The areas inside and outside the ends of the stents were evaluated in each case after animal sacrifice. After testing statistical significance of data for RUG and histologic findings in the four study groups, the Mann-Whitney U test was used to compare groups I and II to determine delayed effects of irradiation, groups I and III to determine benefits of delayed irradiation, groups I and IV to determine efficacy of immediate irradiation for reducing tissue hyperplasia, and groups III and IV to determine efficacy of delayed irradiation for reducing tissue hyperplasia. RESULTS: There were no significant differences in the four study groups on RUG before animal sacrifice. Between groups I and II, group II showed significantly lower mean values in five of six histologic comparisons. Between groups I and III, group III showed significantly lower mean values in only papillary projection thickness inside the stent ends. Between groups I and IV, group I showed significantly lower mean values in all three histologic parameters outside the stent ends. Between groups III and IV, group III showed significantly lower mean values in only two histologic parameters (papillary projection thickness in the in-stent area and inflammatory cell infiltration outside the stent edges). CONCLUSION: beta-Irradiation with use of a 188-Re MAG(3)-filled balloon shows the potential to reduce tissue hyperplasia secondary to stent placement in a canine urethral model. Treatment with 188-Re MAG(3)-filled balloons at the time of stent placement shows not only favorable outcomes for reducing tissue hyperplasia but also improved delayed effects until 8 weeks.     

Oversizing of self-expanding stents: influence on the development of neointimal hyperplasia of the carotid artery in a canine model

BACKGROUND AND PURPOSE: In carotid artery stent placement, marked oversizing of the stent relative to the internal carotid artery lumen is common. This study was performed to determine the influence of using oversized self-expanding nitinol stents on neointimal hyperplasia. METHODS: In six greyhound dogs, 24 self-expanding nitinol stents (eight SMART stents, eight Easy Wallstents, eight Sinus-Flex stents) were inserted into both common carotid arteries (CCAs). In each CCA, two stents were deployed; a stent of the appropriate diameter was implanted distally and an oversized stent proximally. After 4 months, transverse sections of each stent were examined histologically and at computerized image analysis. Neointimal hyperplasia was determined as the proportion of the residual diameter of the patent vessel lumen compared with the stent lumen. RESULTS: The amount of neointimal hyperplasia did not differ between the normal-sized and oversized stents. The mean preserved luminal diameter (+/-SEM) with normal- and oversized stents, respectively, were as follows: Easy Wallstent, 94% +/- 1.0 and 96% +/- 1.5; SMART stent, 92% +/- 1.6 and 93% +/- 1.8; and Sinus-Flex stent, 93% +/- 2.7 and 93% +/- 2.6. The mean preserved patent lumen with the 12 normal-sized stents (93% +/-1.0) was not significantly different from that of the 12 oversized stents (94% +/- 1.1, P =.502). CONCLUSION: Under experimental conditions, use of self-expanding stents oversized by 30-40% appeared to result in neointimal hyperplasia comparable to that caused by normal-sized stents. All three stent types appeared to have similarly low neointimal responses.     

MR imaging of the male and female urethra.

Conventional radiographic contrast material-enhanced studies (eg, retrograde urethrography [RUG], voiding cystourethrography [VCUG], double-balloon catheter urethrography) and ultrasonography are useful in evaluating the anatomy of the urethra but are limited in demonstrating anatomic derangement of adjacent structures. Since the anatomic details of both the urethra and periurethral tissues can be evaluated noninvasively with magnetic resonance (MR) imaging, this modality can be used as an adjunctive tool for evaluation of urethral abnormalities. In patients with congenital anomalies, MR imaging is reserved for cases of intersex anomalies or complex genitourinary anomalies, in which evaluation of internal organs is essential. MR imaging may demonstrate diverticula that are not seen on radiographic contrast-enhanced studies, including VCUG, RUG, or double-balloon catheter study. In cases of inflammation, MR imaging can demonstrate not only inflammatory infiltration around the urethra but also the presence of a periurethral abscess or sinus tract. In cases of trauma, MR imaging is helpful in assessing the presence and extent of anterior or posterior urethral injury and predicting the occurrence of complications. At MR imaging, a fistula can be seen as a direct communicating channel with an adjacent organ. In patients with urethral tumors, the major role of MR imaging is in local staging.     

MRI of prostatic urethral mucinous urothelial carcinoma: Expanding the differential diagnosis for T2 hyperintense prostatic masses

We report the case of a 66-year-old previously healthy man presenting with blood and mucus in his urine. Cystoscopy revealed a mass in the prostatic urethra, and endoscopic biopsy showed adenocarcinoma in situ with mucinous features. Endorectal multiparametric prostate MRI demonstrated a 1.9 cm T2 hyperintense mass in the peripheral zone of the left prostatic apex with extension into the urethral lumen. No diffusion restriction or early enhancement was seen in the mass. Radical prostatectomy was performed, and final pathology demonstrated a mucin-producing urothelial adenocarcinoma arising from the prostatic urethra. The peripheral zone T2 hyperintense abnormality correlated with abundant pools of mucin extending into the prostatic stroma and surrounded by neoplastic prostatic glandular cells. We conclude prostatic urethral mucinous urothelial carcinoma should be included in the differential diagnosis for T2 hyperintense prostatic masses.     

Comparison of a New Polytetrafluoroethylene-Covered Metallic Stent to a Noncovered Stent in Canine Ureters

The aim of this study was to determine the feasibility of using a newly designed polytetrafluoroethylene (PTFE)-covered metallic stent in the ureter by comparing its effectiveness with that of the noncovered stent in a canine model. We placed 14 stents in the ureters of seven mongrel dogs that weighed 30–40 kg each. The covered and noncovered stents were deployed in the right and left ureters, respectively, of six dogs. In the seventh dog, a covered stent and a double-J catheter were inserted in the right ureter, and a covered stent only was inserted in the left ureter. The first six dogs were sacrificed at 5, 10, and 15 weeks after deployment of the stents (two for each follow-up period), and the seventh dog was sacrificed at 30 weeks. There was no migration or poor expansion of any of the stents observed on plain radiography. On intravenous pyelogram and retrograde pyelogram, all of the covered stents at each follow-up period had patent lumens at the stented segments without hydronephrosis, and the passage of contrast material through it was well preserved. The noncovered stents in the dogs sacrificed at 5 and 10 weeks and one of the two dogs sacrificed at 15 weeks showed near-complete occlusion of the stent lumen due to ingrowth of the soft tissue, and severe hydronephrosis was also noted. The noncovered stent in the other dog sacrificed at 15 weeks showed the passage of contrast material without hydronephrosis, but the lumen of the stent was still nearly occluded by the soft tissue. There was no evidence of hydronephrosis or passage disturbance of the contrast material in both ureters of the dog sacrificed at 30 weeks. We conclude that the newly designed PTFE-covered stent effectively prevented the luminal occlusion caused by urothelial hyperplasia compared to the near-total occlusion of the noncovered stents, and no migration of the covered stents was noted.     

Role of MDCT in evaluation of urethral lesions

Objectives

To evaluate the role of multidetector computed tomography (MDCT) in the diagnosis of urethral lesions.

Methods

Thirteen CT urethrography examinations on 13 male patients were performed with 4-MDCT, over a 15 month duration. These patients were clinically examined and a urethral lesion was suspected. The study included recently traumatized patients and patients with suspected urethral lesions. The study was performed by retrograde urethral injection or during micturition after IV contrast injection. 3D-volume rendering (VR) images and VR-multiplanar reconstruction (MPR) sagittal images and virtual images were done.

Results

Out of the 13 patients, two patients were diagnosed having avulsed prostatic urethra.Nine patients were diagnosed having urethral strictures: two at the bulbous urethra (one of them associated with fistulous stricture), five at the membranous urethra (one of them having associated hypospadias) and two at the prostatic urethra. Two postoperative patients with hypospadias were evaluated, one with glans collection and the other with urethral stricture. One patient was diagnosed having urethral neoplasm.

Conclusion

MDCT urethrography is an accurate method in delineating small lesions, site, length, degree of strictures and extraluminal structures.     

Endovaginal magnetic resonance imaging of the female urethra

Magnetic resonance imaging (MRI) is playing an important role in the clinical evaluation of women presenting with urethral symptoms. Voiding cystourethrography, direct urethrography, and pelvic sonography provide limited information on abnormalities that are in continuity with the urethra. On the other hand, urethra and periurethral tissues can be noninvasively evaluated by high-resolution endocavitary MRI. Because of its multiplanar capability and high tissue contrast, endovaginal MRI is an extremely reliable diagnostic test in the evaluation of urethral abnormalities. In this article, the utility of endovaginal MRI in the detection and characterization of a wide spectrum of urethral pathologic conditions, such as congenital anomalies, diverticula, urethritis, and benign and malignant neoplasms, is discussed.     

Imaging the urethra in men and women

This review describes and illustrates the radiologic techniques, normal anatomy, and common congenital and acquired lesions of the urethra in men and women. Voiding cystourethrography and retrograde urethrography are the most common imaging modalities employed in the diagnosis of anatomic lesions of the urethra. The appearance of the urethra may then dictate the need for further functional evaluation with urodynamic studies. Congenital lesions in men include posterior and anterior urethral valves and duplicated urethra. In women, ectopic insertion of the ureter into the urethra is the usual congenital lesion. Acquired urethral lesions include benign prostatic hypertrophy in men and strictures and diverticula in both men and women.