Evaluation of a New Self-expandable Silicone Stent in an Experimental Tracheal Stenosis

doi:10.1378/chest.115.2.496

Chest

Volume 115, Issue 2, February 1999, Pages 496-501

https://doi.org/10.1378/chest.115.2.496 Get rights and content

Study objectives

To assess the usefulness of an animal model for testing new tracheobronchial stents.

Setting

Animal laboratory of a university hospital.

Animals and interventions

In a series with 12 mini-pigs, we induced a stable fibromalacic tracheal stenosis that was 50% to 70% of the normal tracheal diameter. After dilation we inserted a 16 × 40-mm self-expandable silicone stent into the stenotic part of the trachea in 10 of the mini-pigs. Five of the stents had a smooth outer surface, and five had additional silicone retaining spikes. Because of a long stenosis in two of the mini-pigs, two overlapping stents (one smooth and one with spikes) were inserted.

Measurements and results

Stent deployment was successful and resulted in the disappearance of the slight to moderate stridor in all of the mini-pigs. Over a mean (± SD) observation period of 24 days (range, 10 to 41 days), all of the mini-pigs redeveloped stridor. Three of them died unexpectedly of suffocation: in all three a smooth stent had migrated, leading to total obstruction of the stenosis. In total, five of the six smooth stents migrated, and only one of the six spiked stents migrated. There was considerable granulation tissue formation at the ends of all of the stents. In the two control mini-pigs, a 12 × 35-mm Dumon stent was inserted. Both Dumon stents migrated, and one of them had considerable granuloma formation at its ends. At the end of the observation period, all stents were removed endoscopically and were found not to have deteriorated over time.

Conclusions

Our model proved to be suitable for the evaluation of the technical aspects of the Polyflex stent. Spikes on the outer stent surface are more effective in preventing migration than smooth-surface stents. Long-term compatibility, however, seems to be difficult to test with our model because both the Polyflex and the Dumon stents had excessive granulation tissue formation at both ends, a factor which—in the case of the Dumon stent—does not occur to such a degree in benign human airway stenoses. Our results indicate a need for prospective long-term studies in benign human airway stenoses.

Section snippets

Animals

We used a series of almost fully grown mini-pigs (Göttingen Veterinary Faculty; University of Zurich, Switzerland); all were 18 months of age with a mean weight of 35.5 kg. They were kept in the animal facility of the hospital for at least 1 week prior to the start of the study to allow them sufficient time for acclimatization. The local facilities had been inspected by state veterinarians, and the project was approved by the local ethics committee on animal research.

Anesthesia

All surgical and

Results

The use of our modified experimental model resulted in an easily dilated, stable tracheal stenosis of 50% to 70% of the normal diameter in all of the test animals. A repeat application of NaOH was necessary on two occasions because of an insufficient degree of stenosis, but excessive granulation tissue formation with severe respiratory distress and sudden unexpected suffocation was avoided. Balloon dilation of the stenotic passage prevented the rigid bronchoscope from shearing off mucosa and

Discussion

In this study we were able to adapt successfully the experimental pig model of a tracheal stenosis as described by Marquette et al,¹¹ and to prove its usefulness in evaluating all technical aspects of the new self-expandable Polyflex stent. Contrary to the short-term study of Marquette et al,¹¹ we planned a stent experiment of 3 months duration and, therefore, wanted to have adult animals with fully grown airways. For this purpose mini-pigs presented several advantages. At 18 months they were

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Evaluation of cover effects on bare stent mechanical response
2016, Journal of the Mechanical Behavior of Biomedical Materials
Citation Excerpt :
However, these methods are difficult to repeat due to the natural variation in tissue properties. Animal models with surgically created benign stenoses have also been developed (Hugo Marquette et al., 1995; Korpela, 1999; Bolliger et al., 1999) to simulate the loading seen clinically, though useful for examining stent behaviour these methods are neither repeatable nor practical for stent testing. The second aspect of this work investigates the use of a simple bench-top test that could be used to evaluate the effect of airway geometry and deformation on stent response.
Covered tracheobronchial stents are used to prevent tumour growth from reoccluding the airways. In the present work a combination of experimental and computational methods are used to present the mechanical effects that adhered covers can have on stent performance. A prototype tracheobronchial stent is characterised in bare and covered configurations using radial force, flat plate and a novel non-uniform radial force test, while computational modelling is performed in parallel to extensively inform the physical testing. Results of the study show that cover configuration can have a significant structural effect on stent performance, and that stent response (bare or covered) is especially loading specific, highlighting that the loading configuration that a stent is about to be subjected to should be considered before stent implantation.
A rat tracheal model to investigate stent-induced tissue hyperplasia: A pilot study
2010, Journal of Vascular and Interventional Radiology
To evaluate the feasibility of stent placement and the formation of stent-induced tissue hyperplasia and to verify matrix metalloproteinase (MMP) expression in stent-induced tissue hyperplasia in a rat tracheal model.
In a pilot study, four rats were used to verify MMP expression in stent-induced tracheal tissue hyperplasia based on zymography and Western blot analysis. In the main experiment, 12 rats were divided into two groups with different stent-mesh gap sizes (group I, 1.23 × 1.92 mm; group II, 0.80 × 1.80 mm). The stent was 4 mm in diameter and 8 mm long. Follow-up tracheogram was performed before sacrifice 3 weeks after stent placement. The gross and the microscopic findings were evaluated.
Stent placement was technically successful in all rats. During follow-up, two rats (one from each group) died within 4 days after stent placement, and one stent in group II was placed outside the trachea. MMP-9 expression was significantly higher in tissue hyperplasia than in control normal tissue. The excised specimens showed tissue hyperplasia through the mesh, and all of the stents had become incorporated into the wall of the trachea. The papillary projection thickness, granulation tissue area, percentage of granulation tissue area, and degree of inflammatory cell infiltration were higher in group II than in group I, but there was no statistically significant difference.
In this study, stent placement was feasible, and the formation of stent-induced tissue hyperplasia was evident in a rat tracheal model. MMP-9 overexpression was evident in the stent-induced tracheal tissue hyperplasia.
Regulatory acceptability of the minipig in the development of pharmaceuticals, chemicals and other products
2010, Journal of Pharmacological and Toxicological Methods
As part of the RETHINK European FP6 Project an overview of the acceptability and usefulness of minipigs has been carried out in the regulatory arenas of human and veterinary pharmaceuticals, food additives, cosmetics, biocides and agrochemicals, chemicals and medical devices.
The safety of new pharmaceuticals for human use should be tested in non-rodents, but the regulatory world is not too prescriptive regarding the choice of species. The choice is most often dogs through long tradition. When dogs are not appropriate, in many cases non-human primates are chosen as an alternative.
From information in the public domain as well as literature from the EMA and FDA, it is clear that minipigs have already been identified as suitable to take the role of non-rodent species in toxicity testing of pharmaceutical products.
In the field of foodstuffs, the pig is used more extensively because of the apparent similarity in the omnivorous food pattern and digestive tract between humans and pigs. The extensive use of pigs in this field provides historical data.
In the field of medical devices the ISO Guidelines indicate that the pig is regarded as a suitable animal model because of its haematological and cardiovascular similarities to man. The pig is also mentioned as suitable for testing local effects after implantation.
Political and societal support for using nonhuman primates is decreasing, and it is an appropriate time to consider the role of the minipig.
We have reviewed the costs of testing in minipigs, and these are not significantly higher than the costs for a study in dogs. Economical reasons should therefore not be used to argue against the use of minipigs instead of dogs or monkeys.
For most purposes, minipigs may be considered an acceptable choice as non-rodent species, provided adequate justification for this choice is made.
Congenital Malformations of the Lungs and Airways
2008, Pediatric Respiratory Medicine
Polyflex™ stenting of tracheomalacia after surgery for congenital tracheal stenosis
2007, International Journal of Pediatric Otorhinolaryngology
Citation Excerpt :
However, in normal bronchial airways of sheep, two of four stents dislodged within 6 months and all dislodged by 12 months [11]. In experimental fibromalacic tracheal stenosis in small pigs, five of six ‘smooth’ stents migrated (three causing fatal obstruction) while one of six ‘spiked’ stents migrated [12]. We used the smooth version of the Polyflex stent.
Polyflex™ self-expanding stents (Rüsch, Germany) were used in three young children who had presented with life-threatening long-segment tracheal stenosis with bronchial stenosis in two cases. Two children had slide tracheoplasties and subsequently aortic homografts and another tracheal resection and autotracheoplasty. However, in all cases persistent lower tracheal malacia necessitated stenting. Complications of granuloma, stent migration or dislodgement occurred in all cases. A fatal tracheo-aortic fistula occurred in one child. Granuloma in one was treated successfully with steroids. One child survives.
Performance of a self-expanding silicone stent in palliation of benign airway conditions
2006, Chest
Citation Excerpt :
This was the basis of our selection of the Polyflex silicone stent. Besides its thin wall structure, its self-expanding property and radioopaque ends were appealing.5,6 We were also intrigued by its performance in patients with malignancies.6,7
The Polyflex stent (Boston Scientific; Boston, MA) is a self-expanding, thin-walled, silicone stent. Its use has been described in the management of patients with malignant airway obstruction, yet reports of its use for treatment of benign airway conditions are rare.
We report a retrospective review of our experience with the Polyflex stent in the management of benign airway conditions.
A total of 16 stents were deployed in 12 patients. The indications for the stent placement included the following: anastomotic stenosis following lung transplantation (LTR) [four patients]; tracheal stenosis (three patients); tracheobronchomalacia (two patients); tracheobronchopathiaosteochondroplastica (one patient); relapsing polychondritis (one patient); and bronchopleural fistula (one patient). Even though immediate palliation was established in most cases (90%), the incidence of complications was 75%. Stent migration was the most common consequence, with time to the event ranging from < 24 h to 7 months. One stent was expectorated within < 24 h. One patient coughed up a portion of the inner lining of the stent 7 months after its placement. Emergent bronchoscopy was required in four patients for mucous impaction. The complication rate was 100% in patients with LTR-related anastomotic stenosis.
The use of the Polyflex stent for the treatment of benign airway conditions is associated with a high complication rate. We have abandoned its use under such conditions in our practice.

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Supported by the Foundation of Pneumology, Basel, Switzerland; and Rüsch AG, Kernen, Germany

For related material see pages 490 and 532.

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Chest

Laboratory and Animal InvestigationsEvaluation of a New Self-expandable Silicone Stent in an Experimental Tracheal Stenosis

Study objectives

Setting

Animals and interventions

Measurements and results

Conclusions

Section snippets

Animals

Anesthesia

Results

Discussion

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Airway stents

Semin Respir Crit Care Med

Laboratory and Animal Investigations
Evaluation of a New Self-expandable Silicone Stent in an Experimental Tracheal Stenosis