Background Over 80,000 people undergo pulmonary resection for a lung nodule in the United States each year. Small nodules are frequently missed or difficult to find despite preoperative imaging. We hypothesized that near-infrared (NIR) imaging technology could be used to identify and locate lung nodules during surgery. Methods We enrolled 18 patients who were diagnosed with a pulmonary nodule that required resection. All patients had a fine-cut 1mm computed tomography scan preoperatively. The patients were given systemic 5 mg/kg indocyanine green (ICG) and then underwent an open thoracotomy 24 hours later. NIR imaging was used to identify the primary nodule and search for additional nodules that were not found by visual inspection or manual palpation of the ipsilateral lung. Results Manual palpation and visual inspection identified all 18 primary pulmonary nodules and no additional lesions. Intraoperative NIR imaging detected 16 out of the 18 primary nodules. NIR imaging also identified 5 additional subcentimeter nodules: 3 metastatic adenocarcinomas and 2 metastatic sarcomas. This technology could identify nodules as small as 0.2 cm and as deep as 1.3 cm from the pleural surface. This approach discovered 3 nodules that were in different lobes than the primary tumor. Nodule fluorescence was independent of size, metabolic activity, histology, tumor grade and vascularity. Conclusions This is the first-in-human demonstration of identifying pulmonary nodules during Thoracic surgery with NIR imaging without a priori knowledge of their location or existence. NIR imaging can detect pulmonary nodules during lung resections that are poorly visualized on computed tomography and difficult to discriminate on finger palpation.

IntroductionDefining tumor from non-tumor tissue is one of the major challenges of cancer surgery. Surgeons depend on visual and tactile clues to select which tissues should be removed from a patient. Recently, we and others have hypothesized near-infrared (NIR) imaging can be used during surgery to differentiate tumors from normal tissue.MethodsWe enrolled 8 canines and 5 humans undergoing cancer surgery for NIR imaging. The patients were injected with indocyanine green (ICG), an FDA approved non-receptor specific NIR dye that accumulates in hyperpermeable tissues, 16–24 hours prior to surgery. During surgery, NIR imaging was used to discriminate the tumor from non-tumor tissue.ResultsNIR imaging identified all tumors with a mean signal-to-background ratio of 6.7. Optical images were useful during surgery in discriminating normal tissue from cancer. In 3 canine cases and 1 human case, the tissue surrounding the tumor was inflamed due to obstruction of the vascular supply due to mass effect. In these instances, NIR imaging could not distinguish tumor tissue from tissue that was congested, edematous and did not contain cancer.ConclusionsThis study shows that NIR imaging can identify tumors from normal tissues, provides excellent tissue contrast, and it facilitates the resection of tumors. However, in situations where there is significant peritumoral inflammation, NIR imaging with ICG is not helpful. This suggests that non-targeted NIR dyes that accumulate in hyperpermeable tissues will have significant limitations in the future, and receptor-specific NIR dyes may be necessary to overcome this problem.

Systemic ICG reliably accumulates in breast cancers in murine models as well as human breast cancer. While NIR imaging is helpful for detection of retained tumor margins in our animal model, intraoperative imaging for precise margin detection will need further refinement before clinical value can be obtained. J. Surg. Oncol. 2016;113:508-514. © 2016 Wiley Periodicals, Inc.

Background Over 80,000 people undergo resection of a pulmonary tumor each year, and the only method to determine if the tumor is malignant is histological analysis. We propose that a targeted molecular contrast agent could bind lung adenocarcinomas and then identify these tumors by real-time optical imaging at the time of surgery. Methods Fifty patients with a biopsy-proven lung adenocarcinoma were enrolled. Prior to surgery, patients were systemically administered 0.1 mg/kg of a fluorescent folate receptor alpha (FRα)-targeted molecular contrast agent by intravenous infusion. During surgery, tumors were imaged in situ and ex vivo after dissecting the lung parenchyma to directly expose the tumor to the imaging system. Results Tumors ranged from 0.3—7.5 cm (mean 2.6cm), and 46/50 (92%) lung adenocarcinomas were fluorescent. There was no false uptake, and in 2 cases, intraoperative imaging discovered tumor metastases (3mm and 6mm) that were not recognized preoperatively. Four adenocarcinomas were not fluorescent, and immunohistochemistry showed these adenocarcinomas did not express FRα. Tumor fluorescence was independent of nodule size, 18FDG uptake, histology, and tumor differentiation. Molecular imaging could only identify 7 out of the 50 adenocarcinomas in situ in the patient without bisection. The most important predictor of molecular imaging to locate the tumor in situ was the distance of the nodule from the pleural surface. Conclusions Intraoperative molecular imaging with a targeted contrast agent can identify lung adenocarcinomas, and this technology is currently useful in patients with subpleural tumors irrespective of size. With further refinements, this tool may prove useful in locating adenocarcinomas deeper in the lung parenchyma, lymph nodes and at pleural and resection margins.

INBU is feasible in the SICU and is equivalent to central venous pressure in assessing volume status. Noninvasive methods to assess volume status may decrease the need for invasive procedures.

No abstract

These data suggest that combining IMI with PET may provide superior oncologic outcomes for patients with resectable lung cancer.

Abstract. Surgery is the most effective method to cure patients with solid tumors, and 50% of all cancer patients undergo resection. Local recurrences are due to tumor cells remaining in the wound, thus we explore near-infrared (NIR) fluorescence spectroscopy and imaging to identify residual cancer cells after surgery. Fifteen canines and two human patients with spontaneously occurring sarcomas underwent intraoperative imaging. During the operation, the wounds were interrogated with NIR fluorescence imaging and spectroscopy. NIR monitoring identified the presence or absence of residual tumor cells after surgery in 14∕15 canines with a mean fluorescence signal-to-background ratio (SBR) of ∼16. Ten animals showed no residual tumor cells in the wound bed (mean SBR < 2, P < 0.001). None had a local recurrence at >1-year follow-up. In five animals, the mean SBR of the wound was >15, and histopathology confirmed tumor cells in the postsurgical wound in four/five canines. In the human pilot study, neither patient had residual tumor cells in the wound bed, and both remain disease free at >1.5-year follow up. Intraoperative NIR fluorescence imaging and spectroscopy identifies residual tumor cells in surgical wounds. These observations suggest that NIR imaging techniques may improve tumor resection during cancer operations.