Novel Image-Guided Percutaneous Lung Tissue Excision Device With Integrated Sealing of Blood Vessels and Airways: An In Vivo Preclinical Study.

OBJECTIVE: This study evaluated the efficacy of the Minimally Invasive Targeted Resection (MiTR) device, a novel electrosurgical instrument that allows for targeted excision of a lung abnormality while using bipolar radiofrequency (RF) energy to seal blood vessels and airways. METHODS: The MiTR system was evaluated in 7 acute and 2 chronic porcine (7-day) models to evaluate the efficacy of tissue excision with bipolar RF sealing of blood vessels and airways and application of an autologous blood patch into the excised tissue cavity. Air leak was recorded for all evaluations. The study was approved by the institutional ethical board. RESULTS: Nineteen lung tissue samples, measuring 2.5 cm long × 1.2 cm diameter, were excised. In 8 of 9 animals (89%), hemostasis and pneumostasis were observed visually at the completion of the procedure. In 2 of 2 chronic animals (100%), hemostasis and pneumostasis persisted for the 7-day observation period. Histologic examination of the excised samples showed preservation of the core parenchymal architecture without evident tissue damage of the samples that would impair pathologic analysis. CONCLUSIONS: Percutaneous resection of targeted lung tissue with the MiTR system demonstrated hemostasis and pneumostasis while obtaining a histologically intact sample. After regulatory approval, the use of this device could offer more tissue for analysis than a transthoracic needle biopsy or bronchoscopy and a far less invasive alternative to video-assisted thoracic surgery or thoracotomy. This may also expand patient and physician options for the early diagnosis and treatment of lung cancer.

Phenotypic Basis for Matrix Stiffness-Dependent Chemoresistance of Breast Cancer Cells to Doxorubicin.

The persistence of drug resistant cell populations following chemotherapeutic treatment is a significant challenge in the clinical management of cancer. Resistant subpopulations arise via both cell intrinsic and extrinsic mechanisms. Extrinsic factors in the microenvironment, including neighboring cells, glycosaminoglycans, and fibrous proteins impact therapy response. Elevated levels of extracellular fibrous proteins are associated with tumor progression and cause the surrounding tissue to stiffen through changes in structure and composition of the extracellular matrix (ECM). We sought to determine how this progressively stiffening microenvironment affects the sensitivity of breast cancer cells to chemotherapeutic treatment. MDA-MB-231 triple negative breast carcinoma cells cultured in a 3D alginate-based hydrogel system displayed a stiffness-dependent response to the chemotherapeutic doxorubicin. MCF7 breast carcinoma cells cultured in the same conditions did not exhibit this stiffness-dependent resistance to the drug. This differential therapeutic response was coordinated with nuclear translocation of YAP, a marker of mesenchymal differentiation. The stiffness-dependent response was lost when cells were transferred from 3D to monolayer cultures, suggesting that endpoint ECM conditions largely govern the response to doxorubicin. To further examine this response, we utilized a platform capable of dynamic ECM stiffness modulation to allow for a change in matrix stiffness over time. We found that MDA-MB-231 cells have a stiffness-dependent resistance to doxorubicin and that duration of exposure to ECM stiffness is sufficient to modulate this response. These results indicate the need for additional tools to integrate mechanical stiffness with therapeutic response and inform decisions for more effective use of chemotherapeutics in the clinic.