Luke G. Gutwein

Evaluation of breast tumor margins in vivo with intraoperative photoacoustic imaging

The use of photoacoustic effect is a promising approach for biomedical imaging in living tissues. Photoacoustic tomography (PAT) has been demonstrated to image breast cancer, brain vasculature, arthritis and seizure focus owing to its rich optical contrast and high resolution in a single imaging modality. Here we report a microelectromechanical systems (MEMS)-based intraoperative PAT (iPAT) technique, and demonstrate its ability to accurately map tumors in three-dimension and to inspect the completeness of tumor resection during surgery in a tumor-bearing mouse model. The MEMS imaging probe is small and has the potential to be conveniently used to guide surgical resection of tumors in the breast.

Utilization of minimally invasive breast biopsy for the evaluation of suspicious breast lesions

BACKGROUND Percutaneous needle biopsy, also known as minimally invasive breast biopsy (MIBB), has become the gold standard for the initial assessment of suspicious breast lesions. The purpose of this study is to determine modern rates of MIBB and open breast biopsy. METHODS The Florida Agency for Health Care Administration outpatient surgery and procedure database was queried for patients undergoing open surgical biopsy and MIBB between 2003 and 2008. RESULTS Although there was an increase in the use of MIBB, the overall rate of open surgical biopsy remained high (∼30%). A reduction in the open biopsy rate from 30% to 10% could be associated with a charge reduction of >

Multi-dye theranostic nanoparticle platform for bioimaging and cancer therapy

37.2 million per year. CONCLUSIONS The current rate of open surgical breast biopsy remains high. Interventions and quality initiatives are warranted, which could lead to a reduction in unnecessary operations for women, improved patient care, and a reduction in breast health care costs.

Nanoparticle delivery for metastatic breast cancer

Background Theranostic nanomaterials composed of fluorescent and photothermal agents can both image and provide a method of disease treatment in clinical oncology. For in vivo use, the near-infrared (NIR) window has been the focus of the majority of studies, because of greater light penetration due to lower absorption and scatter of biological components. Therefore, having both fluorescent and photothermal agents with optical properties in the NIR provides the best chance of improved theranostic capabilities utilizing nanotechnology. Methods We developed nonplasmonic multi-dye theranostic silica nanoparticles (MDT-NPs), combining NIR fluorescence visualization and photothermal therapy within a single nanoconstruct comprised of molecular components. A modified NIR fluorescent heptamethine cyanine dye was covalently incorporated into a mesoporous silica matrix and a hydrophobic metallo-naphthalocyanine dye with large molar absorptivity was loaded into the pores of these fluorescent particles. The imaging and therapeutic capabilities of these nanoparticles were demonstrated in vivo using a direct tumor injection model. Results The fluorescent nanoparticles are bright probes (300-fold enhancement in quantum yield versus free dye) that have a large Stokes shift (>110 nm). Incorporation of the naphthalocyanine dye and exposure to NIR laser excitation results in a temperature increase of the surrounding environment of the MDT-NPs. Tumors injected with these NPs are easily visible with NIR imaging and produce significantly elevated levels of tumor necrosis (95%) upon photothermal ablation compared with controls, as evaluated by bioluminescence and histological analysis. Conclusion MDT-NPs are novel, multifunctional nanomaterials that have optical properties dependent upon the unique incorporation of NIR fluorescent and NIR photothermal dyes within a mesoporous silica platform.

Fractionated photothermal antitumor therapy with multidye nanoparticles.

Breast cancer represents a major ongoing public health problem as the most common non-cutaneous malignancy among U.S. women. While significant progress has been made in improving loco-regional treatments for breast cancer, relatively little progress has been made in diagnosing and treating patients with metastatic breast cancer. At present there are limited curative options for patients with breast cancer metastatic beyond regional nodes. Emerging nanotechnologies promise new approaches to early detection and treatment of metastatic breast cancer. Fulfilling the promise of nanotechnologies for patients with metastatic breast cancer will require delivery of nanomaterials to sites of metastatic disease. Future translational approaches will rely on an ever increasing understanding of the biology of breast cancer subtypes and their metastases. These important concepts will be highlighted and elucidated in this manuscript.

The promise of nanotechnology for solving clinical problems in breast cancer

Purpose Photothermal therapy is an emerging cancer treatment paradigm which involves highly localized heating and killing of tumor cells, due to the presence of nanomaterials that can strongly absorb near-infrared (NIR) light. In addition to having deep penetration depths in tissue, NIR light is innocuous to normal cells. Little is known currently about the fate of nanomaterials post photothermal ablation and the implications thereof. The purpose of this investigation was to define the intratumoral fate of nanoparticles (NPs) after photothermal therapy in vivo and characterize the use of novel multidye theranostic NPs (MDT-NPs) for fractionated photothermal antitumor therapy. Methods The photothermal and fluorescent properties of MDT-NPs were first characterized. To investigate the fate of nanomaterials following photothermal ablation in vivo, novel MDT-NPs and a murine mammary tumor model were used. Intratumoral injection of MDT-NPs and real-time fluorescence imaging before and after fractionated photothermal therapy was performed to study the intratumoral fate of MDT-NPs. Gross tumor and histological changes were made comparing MDT-NP treated and control tumor-bearing mice. Results The dual dye-loaded mesoporous NPs (ie, MDT-NPs; circa 100 nm) retained both their NIR absorbing and NIR fluorescent capabilities after photoactivation. In vivo MDT-NPs remained localized in the intratumoral position after photothermal ablation. With fractionated photothermal therapy, there was significant treatment effect observed macroscopically (P = 0.026) in experimental tumor-bearing mice compared to control treated tumor-bearing mice. Conclusion Fractionated photothermal therapy for cancer represents a new therapeutic paradigm enabled by the application of novel functional nanomaterials. MDT-NPs may advance clinical treatment of cancer by enabling fractionated real-time image guided photothermal therapy.

Nanoparticle delivery for metastatic breast cancer.

Approaches for breast cancer treatment are invasive, disfiguring, have significant side‐effects, and are not always curative. Nanotechnology is an emerging area which is focused on engineering of materials <100 × 10−9 m. There is significant promise for advancing nanotechnology to improve breast cancer diagnosis and treatment including non‐invasive therapy, monitoring response to therapy, advanced imaging, treatment of metastatic disease, and improved nodal staging. Current approaches and important future directions are discussed. J. Surg. Oncol. 2011; 103:317–325.

Use of video-assisted thoracoscopic surgery in penetrating chest trauma

Breast cancer represents a major ongoing public health problem as the most common non-cutaneous malignancy among U.S. women. While significant progress has been made in improving loco-regional treatments for breast cancer, relatively little progress has been made in diagnosing and treating patients with metastatic breast cancer. At present there are limited curative options for patients with breast cancer metastatic beyond regional nodes. Emerging nanotechnologies promise new approaches to early detection and treatment of metastatic breast cancer. Fulfilling the promise of nanotechnologies for patients with metastatic breast cancer will require delivery of nanomaterials to sites of metastatic disease. Future translational approaches will rely on an ever increasing understanding of the biology of breast cancer subtypes and their metastases. These important concepts will be highlighted and elucidated in this manuscript.

Tumor Endothelial Marker 8 Expression in Triple-negative Breast Cancer

FIGURE 2. Thoracoscopic view of a foreign body penetrating the chest wall and lung. A 27-year-old man, alert and previously healthy, was evaluated at the emergency department immediately after a laboratory explosion. Physical examination revealed normal hemodynamics, a burn injury to his face, and small lacerations across the patient’s chest and abdomen. Visible glass was removed, and the lacerations were irrigated. Computed tomographic images of the chest, abdomen, and pelvis indicated the presence of a large foreign body in the musculature of the right side of the chest, extending into the upper lobe of the right lung (Figure 1). The patient underwent video-assisted thoracoscopic surgery on the right side of the chest and thoracostomy tube placement. He was found to have a foreign body penetrating the chest wall and right lung (Figure 2). Gross examination revealed glass, consistent with a beaker fragment. The patient was discharged home on postoperative day 4 with no complications. As compared with thoracotomy, video-assisted thoracoscopic surgery has many advantages: lower incidence of wound and pulmonary complications, less analgesia required, a shorter time to resumption of normal activity, and higher patient satisfaction. Video-assisted thoracoscopic surgery has proved to be an alternative approach to treating patients in hemodynamically stable condition with blunt and penetrating thoracic injuries. In a metaanalysis, thoracoscopy was shown to prevent 62% of trauma patients from undergoing a thoracotomy or laparotomy, with a 2% complication rate and a 0.8%missed injury rate.