274. Near-infrared Needle-based Confocal Laser Endomicroscopy (NIR-nCLE) May Identify Malignant Cells at Parenchymal Staple Lines in Real-time
University Hospitals Cleveland Medical Center
Cleveland, OH
United States - Contact Me
Dr. Linden attended the University of Pennsylvania School of Medicine and trained in general surgery and cardiothroacic surgery at Brigham and Women's Hospital and Harvard Medical School. He was a staff surgeon at Brigham and Women's Hospital and Harvard Medical School before starting the Division of Thoracic and Esophageal Surgery at University Hospitals of Cleveland. He is currently Chief of Thoracic Surgery at University Hospitals Cleveland Medical Center and Professor of Surgery at The Case Western Reserve University School of Medicine. He started the cardiothoracic fellowship at Case Western Reserve University and is currently the Program Director. He is the Surgical Director of the Seidman Comprehensive Cancer Center of Cleveland.
The Ohio State University
United States - Contact Me
Patrick Bou-Samra completed his third-year of general surgery resident at The Ohio State University. He was a merit scholar at the American University of Beirut where he received his BSc in Biology and graduated summa cum laude. He then completed medical school at the American University of Beirut Medical Center after which he pursued a post-doc research fellowship at The University of Pittsburgh Medical Center. There, he studied frailty and oncologic outcomes in the hepatopancreaticobiliary cohort and psychosocial determinants of health. He then completed his first 2 years of general surgical residency training at The Johns Hopkins Hospital prior to joining The Ohio State University. He is currently in the Singhal lab at Penn interested in improving oncologic outcomes in thoracic malignancies and in intraoperative molecular imaging. He is involved in basic, clinical, and translational research. He also has an interest in surgical education. He plans to pursue a career in academic thoracic surgery.
Abstract
During wedge resections of ground glass opacities, it can be difficult to ascertain negative margins on the parenchymal staple lines by palpation or visualization alone. Frozen section is prone to human error, time consumptive and often difficult to remove staples real-time. We propose a new technology, near-infrared needle-based confocal laser endomicroscopy (NIR-nCLE) to study the presence of cancer cells along the staple line real time during surgery. Our technology utilizes intraoperative molecular imaging with a targeted fluorescent dye and a NIR confocal probe.
Method:
A549 cells (human lung adenocarcinoma cell lines) were co-cultured with a targeted fluorescent probe to cathepsin activity (VGT-309) in an Eppendorf and were compared to a negative and positive control. Fluorescence was measured after 2 hours using Iridium Vision Sense Imaging System (Vision Sense, New York, NY). As a proof of concept, we used normal lung parenchyma from a patient with a negative staple line and injected it with A549-VGT309 cells at two separate locations with 3 x106 and 4.5 x 106 cells. We then translated this data into a murine lung cancer model. Finally, the probe was used over the staple line of a resected tumor from patients who received VGT-309 to assess for any residual disease in real-time. NIR-nCLE probe and ImageJ were used to measure the mean fluorescence intensity (MFI).
Results:
Fluoresce intensity in A549-VGT in an Eppendorf was 71.8a.u, compared to 12.84a.u in our negative control, confirming selective fluorescence in cancer cells. In our proof of concept model, the sites injected with A549-VGT had a MFI of 147.55 arbitrary units (a.u) and 145.37a.u respectively, which was significantly higher than the negative staple line mean of 55.4a.u (p<0.001). Finally, in our pilot clinical model (n=3), tumor MFI was 175.42a.u and 218.78a.u compared to 49.2a.u and 54.6a.u respectively in normal lung parenchyma (p<0.001). We also had an MFI of 55.83a.u on normal parenchyma compared to 50.55a.u on a negative staple line margin (p=0.2) (figure 1).
Conclusion:
NIR-nCLE can detect VGT-targeted cancer cells along a staple line, providing surgeons with a rapid confirmation of their R0 resection. We hypothesize that this technology can be integrated into the OR workflow to expedite surgical decision making and minimize waiting time on pathology with real-time feedback to the surgeon.