Core needle biopsy with endobronchial ultrasonography: single center experience with 100 cases.

INTRODUCTION: Adequate sampling by endobronchial ultrasound (EBUS)-transbronchial needle aspiration to meet the demands of precision medicine or histologic evaluation is challenging. There is increasing demand for core biopsy specimens with advances in therapy. Franseen enodoscopic ultrasound needles have shown promising results in gastroenterology application for obtaining core biopsies and same design has recently been extended for pulmonary use. We evaluated Franseen needles with EBUS to assess its utility, safety and ability to provide core biopsy specimens. MATERIALS AND METHODS: Retrospective analysis of our database at the University of Utah of patients undergoing EBUS with a Franseen needle was performed to ascertain the performance characteristics of this needle in the first 100 patients after its implementation. Medical records were also reviewed to identify any immediate procedure-related complications. RESULTS: One hundred seventy locations were sampled in 100 patients. A total of 152 lymph nodes and 18 masses were sampled. Core biopsies, as per pathology report, were seen in 87% of patients. A clinically concordant pathological diagnosis was established in 97% of patients. Diagnostic yield for granulomatous lymphadenopathy was 95.6% (22 of 23). No patient-related adverse events were noted. CONCLUSION: The Franseen needle evaluated in this study can safely procure core tissue samples during EBUS bronchoscopy that are adequate for histopathological diagnosis in benign and malignant lesions. Its ability to provide adequate tissue in patients with granulomatous inflammation is encouraging.

Chordoma dedifferentiation after proton beam therapy: a case report and review of the literature.

BACKGROUND: Chordoma is a rare invasive bone tumor that may occur anywhere along the neuraxis. A total of three primary histological varieties have been identified: conventional, chondroid, and dedifferentiated. CASE PRESENTATION: We report a case of an 8-year-old white girl who presented with conventional chordoma, was treated with surgical resection and mixed proton and photon beam therapy, and had a recurrence in the resection cavity 2.5 years later with dedifferentiated morphology. The recurrent tumor did not express brachyury, a recently identified protein specific to tissue of notochordal origin. CONCLUSIONS: The short time period between radiation therapy and dedifferentiation, low dose of photons, and rarity of dedifferentiated skull base chordomas in pediatric patients should alert clinicians to the possibility of chordoma dedifferentiation after proton beam therapy.

Macrophage delivery of nanoformulated antiretroviral drug to the brain in a murine model of neuroAIDS.

Antiretroviral therapy (ART) shows variable blood-brain barrier penetration. This may affect the development of neurological complications of HIV infection. In attempts to attenuate viral growth for the nervous system, cell-based nanoformulations were developed with the focus on improving drug pharmacokinetics. We reasoned that ART carriage could be facilitated within blood-borne macrophages traveling across the blood-brain barrier. To test this idea, an HIV-1 encephalitis (HIVE) rodent model was used where HIV-1-infected human monocyte-derived macrophages were stereotactically injected into the subcortex of severe combined immunodeficient mice. ART was prepared using indinavir (IDV) nanoparticles (NP, nanoART) loaded into murine bone marrow macrophages (BMM, IDV-NP-BMM) after ex vivo cultivation. IDV-NP-BMM was administered i.v. to mice resulting in continuous IDV release for 14 days. Rhodamine-labeled IDV-NP was readily observed in areas of HIVE and specifically in brain subregions with active astrogliosis, microgliosis, and neuronal loss. IDV-NP-BMM treatment led to robust IDV levels and reduced HIV-1 replication in HIVE brain regions. We conclude that nanoART targeting to diseased brain through macrophage carriage is possible and can be considered in developmental therapeutics for HIV-associated neurological disease.

Facilitated monocyte-macrophage uptake and tissue distribution of superparmagnetic iron-oxide nanoparticles.

BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery. METHODS: Monocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was synthesized by covalent linkage and uptake into monocytes and MDM investigated related to size, time, temperature, concentration, and coatings. SPIO and IgG SPIO were infused intravenously into naïve mice. T(2) measures using magnetic resonance imaging (MRI) were used to monitor tissue distribution in animals. RESULTS: Oxidation of dextran on the SPIO surface generated reactive aldehyde groups and permitted covalent linkage to amino groups of murine and human IgG and F(ab')(2) fragments and for Alexa Fluor(R) 488 hydroxylamine to form a Schiff base. This labile intermediate was immediately reduced with sodium cyanoborohydride in order to stabilize the NP conjugate. Optical density measurements of the oxidized IgG, F(ab')(2), and/or Alexa Fluor(R) 488 SPIO demonstrated approximately 50% coupling yield. IgG-SPIO was found stable at 4 degrees C for a period of 1 month during which size and polydispersity index varied little from 175 nm and 200 nm, respectively. In vitro, NP accumulated readily within monocyte and MDM cytoplasm after IgG-SPIO exposure; whereas, the uptake of native SPIO in monocytes and MDM was 10-fold less. No changes in cell viability were noted for the SPIO-containing monocytes and MDM. Cell morphology was not changed as observed by transmission electron microscopy. Compared to unconjugated SPIO, intravenous injection of IgG-SPIO afforded enhanced and sustained lymphoid tissue distribution over 24 hours as demonstrated by MRI. CONCLUSIONS: Facilitated uptake of coated SPIO in monocytes and MDM was achieved. Uptake was linked to particle size and was time and concentration dependent. The ability of SPIO to be rapidly taken up and distributed into lymphoid tissues also demonstrates feasibility of macrophage-targeted nanoformulations for diagnostic and drug therapy.

Ingress of blood-borne macrophages across the blood-brain barrier in murine HIV-1 encephalitis.

Blood-borne macrophage ingress into brain in HIV-1 associated neurocognitive disorders governs the tempo of disease. We used superparamagnetic iron-oxide particles loaded into murine bone marrow-derived macrophages (BMM) injected intravenously into HIV-1 encephalitis mice to quantitatively assess BMM entry into diseased brain regions. Magnetic resonance imaging tests were validated by histological coregistration and enhanced image processing. The demonstration of robust BMM migration into areas of focal encephalitis provide 'proof of concept' for the use of MRI to monitor macrophage ingress into brain.