Stereotactic core needle breast biopsy marker migration: An analysis of factors contributing to immediate marker migration.

OBJECTIVES: To evaluate breast biopsy marker migration in stereotactic core needle biopsy procedures and identify contributing factors. METHODS: This retrospective study analyzed 268 stereotactic biopsy markers placed in 263 consecutive patients undergoing stereotactic biopsies using 9G vacuum-assisted devices from August 2010-July 2013. Mammograms were reviewed and factors contributing to marker migration were evaluated. Basic descriptive statistics were calculated and comparisons were performed based on radiographically-confirmed marker migration. RESULTS: Of the 268 placed stereotactic biopsy markers, 35 (13.1%) migrated ≥1 cm from their biopsy cavity. Range: 1-6 cm; mean (± SD): 2.35 ± 1.22 cm. Of the 35 migrated biopsy markers, 9 (25.7%) migrated ≥3.5 cm. Patient age, biopsy pathology, number of cores, and left versus right breast were not associated with migration status (P> 0.10). Global fatty breast density (P= 0.025) and biopsy in the inner region of breast (P = 0.031) were associated with marker migration. Superior biopsy approach (P= 0.025), locally heterogeneous breast density, and t-shaped biopsy markers (P= 0.035) were significant for no marker migration. CONCLUSIONS: Multiple factors were found to influence marker migration. An overall migration rate of 13% supports endeavors of research groups actively developing new biopsy marker designs for improved resistance to migration. KEY POINTS: • Breast biopsy marker migration is documented in 13% of 268 procedures. • Marker migration is affected by physical, biological, and pathological factors. • Breast density, marker shape, needle approach etc. affect migration. • Study demonstrates marker migration prevalence; marker design improvements are needed.

Polymer film-nanoparticle composites as new multimodality, non-migrating breast biopsy markers.

OBJECTIVES: To develop a breast biopsy marker that resists fast and slow migration and has permanent visibility under commonly used imaging modalities. METHODS: A polymer-nanoparticle composite film was prepared by embedding superparamagnetic iron oxide nanoparticles and a superelastic Nitinol wire within a flexible polyethylene matrix. MRI, mammography, and ultrasound were used to visualize the marker in agar, ex vivo chicken breast, bovine liver, brisket, and biopsy training phantoms. Fast migration caused by the "accordion effect" was quantified after simulated stereotactic, vacuum-assisted core biopsy/marker placement, and centrifugation was used to simulate accelerated long-term (i.e., slow) migration in ex vivo bovine tissue phantoms. RESULTS: Clear marker visualization under MRI, mammography, and ultrasound was observed. After deployment, the marker partially unfolds to give a geometrically constrained structure preventing fast and slow migration. The marker can be deployed through an 11G introducer without fast migration occurring, and shows substantially less slow migration than conventional markers. CONCLUSION: The polymer-nanoparticle composite biopsy marker is clearly visible on all clinical imaging modalities and does not show substantial migration, which ensures multimodal assessment of the correct spatial information of the biopsy site, allowing for more accurate diagnosis and treatment planning and improved breast cancer patient care. KEY POINTS: Polymer-nanoparticle composite biopsy markers are visualized using ultrasound, MRI, and mammography. Embedded iron oxide nanoparticles provide tuneable contrast for MRI visualization. Permanent ultrasound visibility is achieved with a non-biodegradable polymer having a distinct ultrasound signal. Flexible polymer-based biopsy markers undergo shape change upon deployment to minimize migration. Non-migrating multimodal markers will help improve accuracy of pre/post-treatment planning studies.

Stretch-Induced Drug Delivery from Superhydrophobic Polymer Composites: Use of Crack Propagation Failure Modes for Controlling Release Rates.

The concept of using crack propagation in polymeric materials to control drug release and its first demonstration are reported. The composite drug delivery system consists of highly-textured superhydrophobic electrosprayed microparticle coatings, composed of biodegradable and biocompatible polymers poly(caprolactone) and poly(glycerol monostearate carbonate-co-caprolactone), and a cellulose/polyester core. The release of entrapped agents is controlled by the magnitude of applied strain, resulting in a graded response from water infiltration through the propagating patterned cracks in the coating. Strain-dependent delivery of the anticancer agents cisplatin and 7-ethyl-10-hydroxycamptothecin to esophageal cancer cells (OE33) in vitro is observed. Finally the device is integrated with an esophageal stent to demonstrate delivery of fluorescein diacetate, using applied tension, to an ex vivo esophagus.

The self-assembly of anticancer camptothecin-dipeptide nanotubes: a minimalistic and high drug loading approach to increased efficacy.

20-(S)-Camptothecin (CPT)-conjugated dipeptides are reported that preassemble into nanotubes with diameters ranging from 80-120 nm. These nanoassemblies maintain a high (∼47 %) drug loading and exhibit greater drug stability (i.e., resistance to lactone hydrolysis), and consequently greater efficacy against several human cancer cells (HT-29, A549, H460, and H23) in vitro compared with the clinically used prodrug irinotecan. A key and defining feature of this system is the use of the CPT-conjugated dipeptide as both the drug and precursor to the nanostructured carrier, which simplifies the overall fabrication process.

Imparting superhydrophobicity to biodegradable poly(lactide-co-glycolide) electrospun meshes.

The synthesis of a family of new poly(lactic acid-co-glycerol monostearate) (PLA-PGC18) copolymers and their use as biodegradable polymer dopants is reported to enhance the hydrophobicity of poly(lactic acid-co-glycolic acid) (PLGA) nonwoven meshes. Solutions of PLGA are doped with PLA-PGC18 and electrospun to form meshes with micrometer-sized fibers. Fiber diameter, percent doping, and copolymer composition influence the nonwetting nature of the meshes and alter their mechanical (tensile) properties. Contact angles as high as 160° are obtained with 30% polymer dopant. Lastly, these meshes are nontoxic, as determined by an NIH/3T3 cell biocompatibility assay, and displayed a minimal foreign body response when implanted in mice. In summary, a general method for constructing biodegradable fibrous meshes with tunable hydrophobicity is described for use in tissue engineering and drug delivery applications.

Mechanoresponsive materials for drug delivery: Harnessing forces for controlled release.

Mechanically-activated delivery systems harness existing physiological and/or externally-applied forces to provide spatiotemporal control over the release of active agents. Current strategies to deliver therapeutic proteins and drugs use three types of mechanical stimuli: compression, tension, and shear. Based on the intended application, each stimulus requires specific material selection, in terms of substrate composition and size (e.g., macrostructured materials and nanomaterials), for optimal in vitro and in vivo performance. For example, compressive systems typically utilize hydrogels or elastomeric substrates that respond to and withstand cyclic compressive loading, whereas, tension-responsive systems use composites to compartmentalize payloads. Finally, shear-activated systems are based on nanoassemblies or microaggregates that respond to physiological or externally-applied shear stresses. In order to provide a comprehensive assessment of current research on mechanoresponsive drug delivery, the mechanical stimuli intrinsically present in the human body are first discussed, along with the mechanical forces typically applied during medical device interventions, followed by in-depth descriptions of compression, tension, and shear-mediated drug delivery devices. We conclude by summarizing the progress of current research aimed at integrating mechanoresponsive elements within these devices, identifying additional clinical opportunities for mechanically-activated systems, and discussing future prospects.

Prevention of lung cancer recurrence using cisplatin-loaded superhydrophobic nanofiber meshes.

For early stage lung cancer patients, local cancer recurrence after surgical resection is a significant concern and stems from microscopic disease left behind after surgery. Here we apply a local drug delivery strategy to combat local lung cancer recurrence after resection using non-woven, biodegradable nanofiber meshes loaded with cisplatin. The meshes are fabricated using a scalable electrospinning process from two biocompatible polymers--polycaprolactone and poly(glycerol monostearate-co-caprolactone)--to afford favorable mechanical properties for use in a dynamic tissue such as the lung. Owing to their rough nanostructure and hydrophobic polymer composition, these meshes exhibit superhydrophobicity, and it is this non-wetting nature that sustains the release of cisplatin in a linear fashion over ∼90 days, with anti-cancer efficacy demonstrated using an in vitro Lewis Lung carcinoma (LLC) cell assay. The in vivo evaluation of cisplatin-loaded superhydrophobic meshes in the prevention of local cancer recurrence in a murine model of LLC surgical resection demonstrated a statistically significant increase (p = 0.0006) in median recurrence-free survival to >23 days, compared to standard intraperitoneal cisplatin therapy of equivalent dose. These results emphasize the importance of supplementing cytoreductive surgery with local drug delivery strategies to improve prognosis for lung cancer patients undergoing tumor resection.

Self-assembly of a 5-fluorouracil-dipeptide hydrogel.

The self-assembly of 5-fluorouracil dilysine conjugates into self-supporting hydrogels, comprised of entangled nanofibers or rigid nanotubes with diameters of 10 and 16 nm, respectively, is reported. The rate of release of 5-Fu from the conjugates was highly dependent on concentration in solution, whereas, release from the fully formed hydrogels was significantly slower. The 5-Fu conjugate also exhibited promising in vitro cytotoxicity against human tumor cell lines A549, H460 and H23.