Alicia Laborda

Magnetic nanoparticles for local drug delivery using magnetic implants

Magnetic nanoparticles are good candidates used for the targeted delivery of anti-tumor agents. They can be concentrated on a desired region, reducing collateral effects and improving the efficiency of the chemotherapy. We propose a method in which permanent magnets are implanted by laparoscopic technique directly in the affected organ. This method proposes the use of Fe@C nanoparticles, which are loaded with doxorubicin and injected intravenously. The particles, once attracted to the magnet, release the drug at the tumor region. This method seems to be more promising and effective than that based on the application of external magnetic fields.

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.

Ten-year Retrospective Study of Treatment of Malignant Colonic Obstructions with Self-expandable Stents

PURPOSE To describe the use of self-expandable metallic stents to manage malignant colorectal obstructions and to compare the radiation dose between fluoroscopic guidance of stent placement and combined endoscopic and fluoroscopic guidance. MATERIALS AND METHODS From January 1998 to December 2007, 467 oncology patients undergoing colorectal stent placement in a single center were included in the study. Informed consent was obtained in all cases. All procedures were performed with fluoroscopic or combined fluoroscopic and endoscopic guidance. Inclusion criteria were total or partial colorectal obstruction of neoplastic origin. Exclusion criteria were life expectancy shorter than 1 month, suspicion of perforation, and/or severe colonic neoplastic bleeding. Procedure time and radiation dose were recorded, and technical and clinical success were evaluated. Follow-up was performed by clinical examination and simple abdominal radiographs at 1 day and at 1, 3, 6, and 12 months. RESULTS Of 467 procedures, technical success was achieved in 432 (92.5%). Thirty-five treatments (7.5%) were technical failures, and the patients were advised to undergo surgery. Significant differences in radiation dose and clinical success were found between the fluoroscopy and combined-technique groups (P < .001). Total decompression was achieved in 372 cases, 29 patients showed remarkable improvement, 11 showed slight improvement, and 20 showed clinical failure. Complications were recorded in 89 patients (19%); the most significant were perforation (2.3%) and stent migration (6.9%). Mean interventional time and radiation dose were 67 minutes and 3,378 dGy·cm(2), respectively. CONCLUSIONS Treatment of colonic obstruction with stents requires a long time in the interventional room and considerable radiation dose. Nevertheless, the clinical benefits and improvement in quality of life justify the radiation risk.

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 subjects health in any of the studied cases.

Influence of breathing movements and Valsalva maneuver on vena caval dynamics

AIM To study changes produced within the inferior vena cava (IVC) during respiratory movements and identify their possible clinical implications. METHODS This study included 100 patients (46 women; 54 men) over 18 years of age who required an abdominal computed tomography (CT) and central venous access. IVC cross-sectional areas were measured on CT scans at three levels, suprarenal (SR), juxtarenal (JR) and infrarenal (IR), during neutral breathing and again during the Valsalva maneuver. All patients were instructed on how to perform a correct Valsalva maneuver. In order to reduce the total radiation dose in our patients, low-dose CT protocols were used in all patients. The venous blood pressure (systolic, diastolic and mean) was invasively measured at the same three levels with neutral breathing and the Valsalva maneuver during venous port implantation. From CT scans, three-dimensional models of the IVC were constructed and a collapsibility index was calculated for each patient. These data were then correlated with venous pressures and cross-sectional areas. RESULTS The mean patient age was 51.64 ± 12.01 years. The areas of the ellipse in neutral breathing were 394.49 ± 85.83 (SR), 380.10 ± 74.55 (JR), and 342.72 ± 49.77 mm(2) (IR), and 87.46 ± 18.35 (SR), 92.64 ± 15.36 (JR) and 70.05 ± 9.64 mm(2) (IR) during the Valsalva (Ps < 0.001). There was a correlation between areas in neutral breathing and in the Valsalva maneuver (P < 0.05 in all areas). Large areas decreased more than smaller areas. The collapsibility indices were 0.49 ± 0.06 (SR), 0.50 ± 0.04 (JR) and 0.50 ± 0.04 (IR), with no significant differences in any region. Reconstructed three-dimensional models showed a flattening of the IVC during Valsalva, adopting an ellipsoid cross-sectional shape. The mean pressures with neutral breathing were 9.44 ± 1.78 (SR), 9.40 ± 1.44 (JR) and 8.84 ± 1.03 mmHg (IR), and 81.08 ± 21.82 (SR), 79.88 ± 19.01 (JR) and 74.04 ± 16.56 mmHg (IR) during Valsalva (Ps < 0.001). There was a negative correlation between cross-sectional caval area and venous blood pressure, but this was not statistically significant in any of the cases. There was a significant correlation between diastolic and mean pressures measured during neutral breathing and in Valsalva. CONCLUSION Respiratory movements have a major influence on IVC dynamics. The increase in intracaval pressure during Valsalva results in a significant decrease in the IVC cross-sectional area.

¿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

Objetivo Estudiar la posibilidad y la seguridad de recuperar filtros opcionales de vena cava Gunther-Tulip (FGT) a los 90 dias de su implantacion inicial en un modelo animal ovino. Material y metodos Se implantaron 30 FGT en otras tantas ovejas hembras y se intento recuperarlos 90 dias despues de su implantacion. Se realizo cavografia convencional en todos los casos antes y despues de la recuperacion, para evaluar la permeabilidad de la vena cava. Se obtuvieron medidas de la vena cava y se documento la presencia de complicaciones relativas a la implantacion y recuperacion del filtro de vena cava inferior (VCI). Se midio la fuerza requerida para recuperar los filtros de vena cava con un dinamometro comercial modificado y adaptado al equipo de recuperacion de FGT. El estudio histologico se centro en la pared de la VCI. Resultados La implantacion se efectuo con exito en todos los casos (100%). Una oveja desarrollo un pequeno foco de trombosis en una de las patas del filtro y otra presento un trombo pequeno en el interior del filtro. Se intento la recuperacion del filtro en las 30 ovejas y, excepto en un caso, el resultado fue satisfactorio (96,6%). En la recuperacion de los 30 FGT, la fuerza necesaria para desenganchar las patas del filtro de la VCI fue menor de 12 newtons (N). No se observo ninguna complicacion en los cavogramas ni en la autopsia. Se observaron diferentes grados de fibrosis en el estudio histologico. Conclusiones En un modelo animal ovino, la recuperacion de FGT a los 90 dias de su implantacion es posible, segura y facil, y requiere poca fuerza (mediana: 4,2 N).

Tratamiento de la hipertensión arterial pulmonar postembólica mediante técnicas mínimamente invasivas guiadas por imagen

Objetivo Aunque la tromboendarterectomia pulmonar quirurgica es el tratamiento de eleccion en la hipertension arterial cronica de origen tromboembolico, cuando no hay indicacion quirurgica o el paciente rechaza la cirugia se puede recurrir a tecnicas endovasculares de minima invasion (angioplastia y protesis metalica) con aceptables resultados. Pacientes y metodos Se trato a 8 pacientes (5 varones y 3 mujeres) con una media de edad de 62,6 anos, en clase III o IV de la clasificacion de la New York Heart Association (NYHA), con presion arterial pulmonar media de 40 mmHg o superior, presion capilar enclavada de 15 mmHg o menor e indice de Miller mayor de 0,5. En todos los casos el diagnostico se establecio por ecografia Doppler cardiaca, angio-grafia pulmonar, estudio hemodinamico y gammagrafia de ventilacion-perfusion. Se realizo tratamiento fibrinolitico seguido de angioplastia en todos los casos, y se coloco una protesis metalica en 3. Se realizaron revisiones clinicas al cabo de 1; 3; 6, y 12 meses mediante ecografia y gammagrafia. Resultados El exito tecnico del procedimiento fue del 100%. El seguimiento medio fue de 18,7 meses. Como complicaciones menores se produjeron extrasistoles en 3 casos; hematoma leve en la zona de puncion en un caso, y rectorra-gia, que remitio sin tratamiento, en otro. Una paciente murio por causa desconocida al cabo de 24 h. En todos los casos revisados se observaron una mejoria en la clasificacion de la NYHA, mejora hemodinamica evidenciada por ecografia y mejora morfologica objetivada por arteriografia y gammagrafia. Conclusiones Las tecnicas endovasculares de minima invasion pueden contribuir a mejorar la hipertension arterial pulmonar cronica debida a tromboembolia en la que no es posible otro tratamiento (farmacologico o quirurgico).

Stents traqueales metálicos autoexpandibles. Estudio comparativo de 3 tipos diferentes de stents en un modelo animal

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.

Removal of Retrievable Inferior Vena Cava Filters 90 Days After Implantation in an Ovine Model: Is There a Time Limit for Removal?

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).