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Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection.

ABSTRACT: BACKGROUND:More than 80,000 people undergo resection of a pulmonary tumor each year, and the only method to determine if the tumor is malignant is histologic analysis. We propose that a targeted molecular contrast agent could bind lung adenocarcinomas, which could be identified using real-time optical imaging at the time of surgery. METHODS:Fifty patients with a biopsy-proven lung adenocarcinoma were enrolled. Before surgery, patients were systemically administered 0.1 mg/kg of a fluorescent folate receptor alpha (FR?)-targeted molecular contrast agent by intravenous infusion. During surgery, tumors were imaged in situ and ex vivo, after the lung parenchyma was dissected to directly expose the tumor to the imaging system. RESULTS:Tumors ranged from 0.3 to 7.5 cm (mean: 2.6 cm), and 46 of 50 (92%) lung adenocarcinomas were fluorescent. No false uptake occurred, and in 2 cases, intraoperative imaging revealed tumor metastases (3 mm and 6 mm) that were not recognized preoperatively. Four adenocarcinomas were not fluorescent, and immunohistochemistry showed that these adenocarcinomas did not express FR?. Tumor fluorescence was independent of nodule size, uptake of 2-deoxy-2-((18)F)fluoro-D-glucose, histology, and tumor differentiation. Molecular imaging could identify only 7 of the 50 adenocarcinomas in situ in the patient without bisection. The most important predictor of the success of molecular imaging in locating 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 that are deeper in the lung parenchyma, in lymph nodes, and at pleural and resection margins.

SUBMITTER: Okusanya OT

PROVIDER: S-EPMC4828933 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection.

Okusanya Olugbenga T OT DeJesus Elizabeth M EM Jiang Jack X JX Judy Ryan P RP Venegas Ollin G OG Deshpande Charuhas G CG Heitjan Daniel F DF Nie Shuming S Low Philip S PS Singhal Sunil S

The Journal of thoracic and cardiovascular surgery 20150507 1

<h4>Background</h4>More than 80,000 people undergo resection of a pulmonary tumor each year, and the only method to determine if the tumor is malignant is histologic analysis. We propose that a targeted molecular contrast agent could bind lung adenocarcinomas, which could be identified using real-time optical imaging at the time of surgery.<h4>Methods</h4>Fifty patients with a biopsy-proven lung adenocarcinoma were enrolled. Before surgery, patients were systemically administered 0.1 mg/kg of a ...[more]

PMID: 26126457

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Project description:BACKGROUND:Intraoperative catastrophes during robotic anatomical pulmonary resections are potentially devastating events. The present study aimed to assess the incidence, management, and outcomes of these intraoperative catastrophes for patients with primary lung cancers. METHODS:This was a retrospective, multiinstitutional study that evaluated patients who underwent robotic anatomical pulmonary resections. Intraoperative catastrophes were defined as events necessitating emergency thoracotomy or requiring an additional unplanned major surgical procedure. Standardized data forms were collected from each institution, with questions on intraoperative management strategies of catastrophic events. RESULTS:Overall, 1810 patients underwent robotic anatomical pulmonary resections, including 1566 (86.5%) lobectomies. Thirty-five patients (1.9%) experienced an intraoperative catastrophe. These patients were found to have significantly higher clinical TNM stage (P = .031) and lower forced expiratory volume in 1 second (81% vs 90%; P = .004). A higher proportion of patients who had a catastrophic event underwent preoperative radiotherapy (8.6% vs 2.3%; P = .048), and the surgical procedures performed differed significantly compared with noncatastrophic patients. Patients in the catastrophic group had higher perioperative mortality (5.7% vs 0.5%; P = .018), longer operative duration (195 minutes vs 170 minutes; P = .020), and higher estimated blood loss (225 mL vs 50 mL; P < .001). The most common catastrophic event was intraoperative hemorrhage from the pulmonary artery, followed by injury to the airway, pulmonary vein, and liver. Detailed management strategies were discussed. CONCLUSIONS:The incidence of catastrophic events during robotic anatomical pulmonary resections was low, and the most common complication was pulmonary arterial injury. Awareness of potential intraoperative catastrophes and their management strategies are critical to improving clinical outcomes.

Project description:PURPOSE:Intraoperative localization and resection of ill-defined pulmonary ground-glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near-infrared molecular imaging with a folate receptor-targeted agent, OTL38, to improve localization of GGOs and confirmation of resection margins. METHODS:In a human trial, 20 subjects with pulmonary GGOs who were eligible for video-assisted thoracoscopic surgery (VATS) resection received 0.025 mg/kg of OTL38 before the resection. The primary objectives were to (1) determine whether use of OTL38 allows safe localization of GGOs and assessment of margins during VATS and (2) determine patient, radiographic, and histopathologic variables that predict the amount of fluorescence during near-infrared imaging. RESULTS:We observed no toxicity. Of the 21 GGOs, 20 accumulated OTL38 and displayed fluorescence upon in situ or back table evaluation. Intraoperatively, near-infrared imaging localized 15 of 21 lesions whereas VATS alone localized 10 of 21 (p = 0.05). The addition of molecular imaging affected care of nine of 21 subjects by improving intraoperative localization (n = 6) and identifying close margins (n = 3). This approach was most effective for subpleural lesions measuring less than 2 cm. For lesions deeper than 1.5 cm from the pleural surface, intraoperative localization using fluorescent feedback was limited. CONCLUSIONS:This approach provides a safe alternative for intraoperative localization of small, peripherally located pulmonary lesions. In contrast to alternative localization techniques, use of OTL38 also allows confirmation of adequate margins. Future studies will compare this approach to alternative localization techniques in a clinical trial.

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Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection.

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Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection.

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