Stent-induced tracheal stenosis can be predicted by IL-8 expression in rabbits.

BACKGROUND: Bare metal stents may cause complications like fibrous encapsulation, granulation and tracheal stenosis. We investigated the behaviour of three commercially available stents in vivo (rabbits) and in vitro (coculture of those stents with epithelial and fibroblast cell lines). Also, we investigated whether development of tracheal stenosis could be predicted by any biological marker. MATERIALS AND METHODS: The tracheae of 30 rabbits were implanted with either nitinol stents, with or without paclitaxel elution, or a cobalt-based stent. An additional ten rabbits underwent mock implantation (controls). Serial peripheral venous blood samples were taken throughout the study, and several cytokines measured. Animals were euthanized on day 90, with immediate tracheal endoscopy and lavage performed, then necropsy. RESULTS: Rabbits with cobalt-based stent exhibited more inflammation and the highest stenosis incidence, with reduced survival. Both in vivo and in vitro, this stent induced higher IL-8 levels than nitinol stents. Most important, the presence of stent-induced tracheal stenosis was closely associated to increase in IL-8 expression in blood just 1 day after tracheal stent implantation: a 1·19-fold increase vs. baseline had 83% sensitivity, 83% specificity, 77% positive predictive value, 88% negative predictive value and 83% accuracy to predict development of stenosis. CONCLUSIONS: The cobalt-based stent had the highest incidence of tracheal inflammation and stenosis. On the other hand, the paclitaxel-eluting nitinol stent did not prevent those complications and provoked a marked reaction compared with the bare nitinol stent. Early increase in IL-8 expression in blood after stent implantation could predict development of tracheal stenosis in rabbits.

Stents traqueales metálicos autoexpandibles. Estudio comparativo de 3 tipos diferentes de stents en un modelo animal / Tracheal Self-Expandable Metallic Stents: A Comparative Study of Three Different Stents in a Rabbit Model

Introducción: El objetivo de este estudio es evaluar l8mm frea reactividad traqueal tras la implantación de distintos stents metálicos autoexpandibles (SMAE). Material y métodos: Se utilizaron 40 conejos hembra de raza neozelandesa, que se dividieron en 4 grupos. En 3 grupos se implantaron SMAE: de acero (SA), de nitinol (NiTi) o stents liberadores de nitinol (SLF). El cuarto grupo fue el grupo de control (sin stent). Los stents se implantaron por vía percutánea bajo control fluoroscópico. Los animales se evaluaron mediante tomografía axial computarizada (TAC) multicorte y las tráqueas se extirparon para su estudio anatomopatológico (EAP). Los datos de la TAC y el EAP se analizaron estadísticamente y se correlacionaron. Resultados: El grupo que recibió SLF presentaba la mayor longitud de estenosis (20,51 ± 14,0nte a 5,84 ± 12,43 y 6,57 ± 6,54 mm en los grupos NiTi y SA, día 30; p < 0,05) y el mayor índice de formación de granulomas evidenciados mediante TAC (50% de los casos). El grupo al que se implantaron stents NiTi mostró el menor grado de estenosis (2,86 ± 6,91% frente a 11,28 ± 13,98 y 15,54 ± 25,95% en los grupos SLF y SA; p<0,05). En el estudio AP, el grupo SA presentó reactividad proliferativa intensa en comparación con los otros 2 grupos. En el grupo SLF se observó una respuesta destructiva en el 70% de animales, mientras que el stent NiTi fue el que menos reacción provocó. La TAC resultó ser superior para detectar el engrosamiento (correlación positiva de un 68,9%; p < 0,001) que para la observación de granulomas (n.s.). Conclusiones: El grupo SA desarrolló granulomas y estenosis significativas. El stent NiTi fue el que menos reacción indujo, mientras que el SLN provocó lesiones importantes que podrían estar relacionadas con la dosis de fármaco. Por consiguiente, este tipo de SLF no se recomienda para el tratamiento de la estenosis traqueobronquial

Introduction: The objective of this study was to assess tracheal reactivity after the deployment of different self-expandable metal stents (SEMS). Material and methods: Forty female New Zealand rabbits were divided into four groups. Three groups received three different SEMS: steel (ST), nitinol (NiTi), or nitinol drug-eluting stent (DES); the fourth group was the control group (no stent). Stents were deployed percutaneously under fluoroscopic guidance. Animals were assessed by multi-slice, computed tomography (CT) scans, and tracheas were collected for anatomical pathology (AP) study. Data from CT and AP were statistically analyzed and correlated. Results: The DES group had the longest stenosis (20.51 ± 14.08 mm vs. 5.84 ± 12.43 and 6.57 ± 6.54 mm in NiTi and ST, respectively, day 30; P < .05), and higher granuloma formation on CT (50% of cases). The NiTi group showed the lowest grade of stenosis (2.86 ± 6.91% vs. 11.28 ± 13.98 and 15.54 ± 25.95% in DES and ST, respectively; P<.05). The AP study revealed that the ST group developed intense proliferative reactivity compared to the other groups. In the DES group, a destructive response was observed in 70% of the animals, while the NiTi was the least reactive stent. CT was more effective in detecting wall thickening (positive correlation of 68.9%; P < .001) than granuloma (not significant). Conclusions: The ST group developed granulomas and significant stenosis. NiTi was the least reactive stent, while DES caused significant lesions that may be related to drug dosage. This type of DES stent is therefore not recommended for the treatment of tracheobronchial stenosis

Tracheal Self-Expandable Metallic Stents: A Comparative Study of Three Different Stents in a Rabbit Model.

INTRODUCTION: The objective of this study was to assess tracheal reactivity after the deployment of different self-expandable metal stents (SEMS). MATERIAL AND METHODS: Forty female New Zealand rabbits were divided into four groups. Three groups received three different SEMS: steel (ST), nitinol (NiTi), or nitinol drug-eluting stent (DES); the fourth group was the control group (no stent). Stents were deployed percutaneously under fluoroscopic guidance. Animals were assessed by multi-slice, computed tomography (CT) scans, and tracheas were collected for anatomical pathology (AP) study. Data from CT and AP were statistically analyzed and correlated. RESULTS: The DES group had the longest stenosis (20.51±14.08mm vs. 5.84±12.43 and 6.57±6.54mm in NiTi and ST, respectively, day 30; P<.05), and higher granuloma formation on CT (50% of cases). The NiTi group showed the lowest grade of stenosis (2.86±6.91% vs. 11.28±13.98 and 15.54±25.95% in DES and ST, respectively; P<.05). The AP study revealed that the ST group developed intense proliferative reactivity compared to the other groups. In the DES group, a destructive response was observed in 70% of the animals, while the NiTi was the least reactive stent. CT was more effective in detecting wall thickening (positive correlation of 68.9%; P<.001) than granuloma (not significant). CONCLUSIONS: The ST group developed granulomas and significant stenosis. NiTi was the least reactive stent, while DES caused significant lesions that may be related to drug dosage. This type of DES stent is therefore not recommended for the treatment of tracheobronchial stenosis.

Pharmacokinetic Study of Paclitaxel Concentration after Drug-Eluting Balloon Angioplasty in the Iliac Artery of Healthy and Atherosclerotic Rabbit Models.

PURPOSE: To assess whether the presence of an atherosclerotic lesion may alter the deposition kinetics of paclitaxel on the arterial wall after drug-eluting balloon (DEB) angioplasty, as well as paclitaxel concentrations in serum and in the recovered balloons. MATERIALS AND METHODS: Three New Zealand White rabbit models were created: an atheroma group (arterial mechanical injury and hyperlipidic diet; group A), a prelesional group (fat arterial infiltration, hyperlipidic diet; group B), and a control healthy group (group C). Forty-five animals underwent DEB angioplasty in the iliac artery. Arteries and serum samples were analyzed by liquid chromatography/tandem mass spectrometry at 1, 24, 48, 72, and 96 hours (arteries) and at 1, 6, 12, and 24 hours (serum). Recovered balloons were analyzed by UV chromatography. Histologic and statistical analyses were also performed. RESULTS: Group A showed significantly higher arterial paclitaxel concentrations in the first hour after DEB angioplasty (632.05 ng/mg ± 125.75 in group A vs 179.55 ng/mg ± 45.64 and 168.54 ng/mg ± 83.48 in groups B and C, respectively; P < .05). Paclitaxel was undetectable in serum at 24 hours in all groups, but the amount was significantly higher (P < .05) in group B at 1, 6, and 12 hours. The paclitaxel amount in navigated balloons from group A was significantly lower than in other groups (P < .05). CONCLUSIONS: Paclitaxel concentration in an atherosclerotic lesion model immediately after DEB angioplasty is nearly fourfold higher than in a healthy artery. Paclitaxel remains in the bloodstream longer when a universal state of fat arterial infiltration is achieved. These findings could have clinical implications, as studies testing commercial drug-eluting devices on healthy animals may be underestimating paclitaxel arterial uptake.

Laparoscopic demonstration of vena cava wall penetration by inferior vena cava filters in an ovine model.

PURPOSE: To verify the penetration of struts and hooks of two inferior vena cava (IVC) filters (Günther tulip retrievable filter [GTF] and Celect filter) through the vena cava wall and to assess local or systemic complications resulting from this penetration. MATERIALS AND METHODS: Eight IVC filters were placed in the IVC of four ewes for 30 days (1 GTF and 1 Celect filter in each ewe). Angiographic and laparoscopic examinations of the animals were performed to demonstrate the penetration through the vena cava wall, and the filters were removed under laparoscopic control. Specimens were extracted for anatomicopathological and histologic examination. RESULTS: Two-projection cavography showed a filter leg seemingly out of the vena cava in 19 of 32 legs (59.3%). Laparoscopy showed 7 real penetrating legs (5 Celect filters and 2 GTFs) out of the 14 legs that could be identified by laparoscopy owing to technique limitations. Neither laparoscopy nor necropsy showed any sign of wall hemorrhage or other injuries. Histologic examination showed intimal remodeling and slight thickening of adventitial tissue around filter legs. CONCLUSIONS: GTFs and Celect filters can produce a real penetration 1 month after implantation. This penetration did not lead to any complications in the IVC or surrounding tissues and did not compromise the subject's health in any of the studied cases.

[Removal of retrievable inferior vena cava filters 90 days after implantation in an ovine model: is there a time limit for removal?]. / Cuál es el tiempo límite para retirar un filtro de vena cava? Filtros opcionales de vena cava inferior: recuperación 90 días después de su implantación. Modelo ovino.

OBJECTIVE: To study the feasibility and safety of removing retrievable Günther-Tulip vena cava filters (GTFs) 90 days after their implantation in an ovine model. MATERIAL AND METHODS: Thirty GTFs were implanted in 30 ewes and retrieval was attempted at 90 days. Conventional cavography was performed in all cases before and after retrieval in order to evaluate inferior vena cava patency and record dimensions. The presence of complications related to placement and retrieval of the filter from the inferior vena cava was also recorded. The force required to remove the filters was measured using a modified commercial dynamometer adapted to the GTF retrieval set. Histologic study focused on the inferior vena cava wall. RESULTS: Implantation was performed successfully in all cases (100%). One ewe developed a small focus of thrombosis around 1 of the legs of the filter and another presented a small thrombus within the filter. Retrieval of the filter was attempted in all 30 sheep at 90 days and the result was satisfactory in all but 1 case (96.6%). None of the GTFs required a force greater than 12 N to disengage the hooks of the filter from the wall. No complications were detected on venacavography or at autopsy. Variable degrees of fibrosis were observed in the histologic study. CONCLUSIONS: Retrieval of GTFs 90 days after implantation in an ovine model was feasible, safe, and easy, and required little force (median, 4.2 N).

¿Cuál es el tiempo límite para retirar un filtro de vena cava? Filtros opcionales de vena cava inferior: recuperación 90 días después de su implantación. Modelo ovino / Removal of retrievable inferior vena cava filters 90 days after implantation in an ovine model: is there a time limit for removal?

OBJETIVO: Estudiar la posibilidad y la seguridad de recuperarfiltros opcionales de vena cava Günther-Tulip (FGT)a los 90 días de su implantación inicial en un modelo animalovino.MATERIAL Y MÉTODOS: Se implantaron 30 FGT en otrastantas ovejas hembras y se intentó recuperarlos 90 días despuésde su implantación. Se realizó cavografía convencionalen todos los casos antes y después de la recuperación, paraevaluar la permeabilidad de la vena cava. Se obtuvieron medidasde la vena cava y se documentó la presencia de complicacionesrelativas a la implantación y recuperación delfiltro de vena cava inferior (VCI). Se midió la fuerza requeridapara recuperar los filtros de vena cava con un dinamómetrocomercial modificado y adaptado al equipo de recuperaciónde FGT. El estudio histológico se centró en lapared de la VCI.RESULTADOS: La implantación se efectuó con éxito en todoslos casos (100%). Una oveja desarrolló un pequeño focode trombosis en una de las patas del filtro y otra presentó untrombo pequeño en el interior del filtro. Se intentó la recuperacióndel filtro en las 30 ovejas y, excepto en un caso, elresultado fue satisfactorio (96,6%). En la recuperación delos 30 FGT, la fuerza necesaria para desenganchar las patasdel filtro de la VCI fue menor de 12 newtons (N). No se observóninguna complicación en los cavogramas ni en la autopsia.Se observaron diferentes grados de fibrosis en el estudiohistológico.CONCLUSIONES: En un modelo animal ovino, la recuperaciónde FGT a los 90 días de su implantación es posible, seguray fácil, y requiere poca fuerza (mediana: 4,2 N)

OBJECTIVE: To study the feasibility and safety of removingretrievable Günther-Tulip vena cava filters (GTFs) 90 daysafter their implantation in an ovine model.MATERIAL AND METHODS: Thirty GTFs were implanted in30 ewes and retrieval was attempted at 90 days. Conventionalcavography was performed in all cases before and afterretrieval in order to evaluate inferior vena cava patency andrecord dimensions. The presence of complications related toplacement and retrieval of the filter from the inferior vena cavawas also recorded. The force required to remove the filters wasmeasured using a modified commercial dynamometer adaptedto the GTF retrieval set. Histologic study focused on the inferiorvena cava wall.RESULTS: Implantation was performed successfully inall cases (100%). One ewe developed a small focus ofthrombosis around 1 of the legs of the filter and anotherpresented a small thrombus within the filter. Retrieval ofthe filter was attempted in all 30 sheep at 90 days and theresult was satisfactory in all but 1 case (96.6%). None ofthe GTFs required a force greater than 12 N to disengage thehooks of the filter from the wall. No complications weredetected on venacavography or at autopsy. Variable degreesof fibrosis were observed in the histologic study.CONCLUSIONS: Retrieval of GTFs 90 days after implantationin an ovine model was feasible, safe, and easy, and requiredlittle force (median, 4.2 N)

Retrieval of Gunther Tulip optional vena cava filters 30 days after implantation: a prospective clinical study.

PURPOSE: To report on the feasibility and safety of retrieval of the Günther Tulip optional vena cava filter 30 days after initial implantation. MATERIALS AND METHODS: From March 2004 to September 2005, a single-center prospective study was undertaken in 35 patients who required inferior vena cava (IVC) filtration. All the Günther Tulip filters (GTFs) were implanted with the intention to be removed 30 days after initial implantation. A modified commercial dynamometer was used to measure the force required to remove the device. The degree of difficulty to remove the GTF was classified into four levels: N (no difficulty, force of 0-4.41 N), M (medium difficulty, force of 4.41-5.88 N), G (great difficulty, force of 5.88-9.8 N), and U (unable to remove). Clinical follow-up was performed 1, 3, 6, and 12 months after filter retrieval by review of medical records and imaging. RESULTS: Two of the 35 patients experienced extensive thrombosis in the IVC as revealed by abdominal computed tomography, and their filters were left in place on a permanent basis. One patient died of respiratory and cardiac failure during follow-up within the first 30 days after GTF insertion. Filter retrieval was attempted in the remaining 32 patients, and 31 of these attempts were successful (98%). The force necessary to disengage the GTF from the caval wall was less than 9.8 N (N, 79%; M, 13%; G, 6%). Attempts to remove the GTF failed in only one patient (2%). On follow-up times ranging between 14 and 640 days (mean, 342.5 d), no complications or cases of recurrent pulmonary embolism were observed in this patient population. CONCLUSION: The Günther Tulip optional IVC filter can be safely placed and retrieved percutaneously 30 days after initial implantation.

Retrievability of uncoated versus paclitaxel-coated Günther-Tulip IVC filters in an animal model.

PURPOSE: To compare in a pilot study, the retrievability and inferior vena cava (IVC) wall reaction elicited by uncoated and paclitaxel-coated Günther-Tulip filters in the animal model. MATERIALS AND METHODS: Three groups with five pigs each underwent infrarenal IVC implantation of Günther-Tulip filters. Paclitaxel-coated filters were used in Groups A and B and uncoated filters were used in Group C. Filters were removed at 14, 19, 22, 26, and 30 days after implantation. A laparotomy was performed to remove filters from animals in group A and filters from animals in groups B and C that could not be retrieved via the right transjugular approach. Filter-induced venous wall changes were evaluated by examination of IVC venography, feasibility of filter removal at different implantation times, and laparotomy and microscopic findings. Feasibility of filter retrieval and venous wall changes were correlated. RESULTS: IVC cavography showed no abnormality. Filters in animals in group B were uneventfully removed by a right jugular approach. Uncoated filter removal was not feasible in three of five animals in group C (19, 22, and 26 days). Microscopically, animals in group A had absent filter-induced IVC wall changes at 14, 19, 22, and 26 days and minimal changes at 30 days post implantation; animals in group B had absent filter-induced IVC wall changes at 14, 19, and 22 days and minimal changes at 26 and 30 days; animals in group C had moderate filter-induced IVC wall changes at 14 days and severe changes at 19, 22, 26, and 30 days. CONCLUSIONS: This pilot study suggests that endothelial reaction to the presence of IVC filters in the porcine model is diminished by addition of paclitaxel coating to these filters. Further studies are necessary to substantiate these results.