Intraoperative near-infrared imaging can identify sub-centimeter colorectal cancer lung metastases during pulmonary metastasectomy

Newton, Andrew D.; Predina, Jarrod D.; Frenzel-Sulyok, Lydia G; Shin, Michael; Wang, Yiqing; Singhal, Sunil

doi:10.21037/jtd.2018.06.161

Cited by 7 publications

(11 citation statements)

References 22 publications

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“…A patient presented for surgical resection of suspected colorectal adenocarcinoma metastases to the lung. Two lesions (one of which was radiographically occult) were identified intraoperatively, as previously reported [ 13 ]. The specimens were sent for frozen section pathology, with the suspected lesions mounted in OCT for sectioning.…”

Section: Resultsmentioning

confidence: 99%

“…The high PPV of Smart-Cut is due to dye localization to the tissue of interest. For example, molecular imaging with TumorGlow ® is highly effective for visualizing pulmonary metastases of sarcoma or colorectal carcinoma, but relatively ineffective for visualization of metastatic melanoma [ 9 , 13 , 16 ]. Consequently, if imaging exclusively with TumorGlow ® , Smart-Cut is hypothesized to be ineffective for metastatic melanoma in the lungs, and for any lesion not receptive to the contrast agent.…”

Section: Discussionmentioning

confidence: 99%

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Molecular imaging can identify the location to perform a frozen biopsy during intraoperative frozen section consultation

et al. 2021

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Background Intraoperative frozen section (FS) consultation is an important tool in surgical oncology that suffers from sampling error because the pathologist does not always know where to perform a biopsy of the surgical specimen. Intraoperative molecular imaging is a technology used in the OR to visualize lesions during surgery. We hypothesized that molecular imaging can address this pathology challenge in FS by visualizing the cancer cells in the specimen in the pathology suite. Here, we report the development and validation of a molecular-imaging capable cryostat called Smart-Cut. Methods A molecular imaging capable cryostat prototype was developed and tested using a murine model. Tumors grown in mice were targeted with a NIR contrast agent, indocyanine green (ICG), via tail vein injection. Tumors and adjacent normal tissue samples were frozen sectioned with Smart-Cut. Fluorescent sections and non-fluorescent sections were prepared for H&E and fluorescent microscopy. Fluorescent signal was quantified by tumor-to-background ratio (TBR). NIR fluorescence was tested in one patient enrolled in a clinical trial. Results The Smart-Cut prototype has a small footprint and fits well in the pathology suite. Fluorescence imaging with Smart-Cut identified cancerous tissue in the specimen in all 12 mice. No false positives or false negatives were seen, as confirmed by H&E. The mean TBR in Smart-Cut positive tissue sections was 6.8 (SD±3.8). In a clinical application in the pathology suite, NIR imaging identified two lesions in a pulmonary resection specimen, where traditional grossing only identified one. Conclusion Molecular imaging can be integrated into the pathology suite via the Smart-Cut device, and can detect cancer in frozen tissue sections using molecular imaging in a murine model.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular imaging can identify the location to perform a frozen biopsy during intraoperative frozen section consultation

et al. 2021

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“…In clinical settings, the maximum dosage of ICG recommended for intravenous injection is 5.0 mg/kg. 17,[37][38][39][40] The frequency of allergic reactions with doses below 0.5 mg/kg was reported as 0.003%, which increased significantly if the dose exceeded 5.0 mg/kg. 41 In addition, inhalation may be applicable to patients with liver disfunction or kidney disfunction by administering a small amount of fluorescent contrast agent.…”

Section: Discussionmentioning

confidence: 99%

“…9,[14][15][16]18 Although the NIR fluorescence signal has depth limitations, it is a feasible intraoperative technique to provide a rapid intraoperative diagnosis, significantly decrease the total operative time, decrease the rate of conversion to open procedures, and allow for more complete removal of tumors, which has been demonstrated by intravenously injected ICG. 9,13,14,17,34,38,39,42 In addition, compared with other soft tissues, such as skin and liver, the lungs undergo volumetric changes through respiratory movements. Thus, the tumor depth in the collapsed lung during surgery was much less than that measured from preoperative chest In healthy lung tissue, inhaled ICG was distributed into the alveoli and phagocytized by alveolar macrophages.…”

Section: Limitationsmentioning

confidence: 99%

Evaluation of Intraoperative Near-Infrared Fluorescence Visualization of the Lung Tumor Margin With Indocyanine Green Inhalation

Jung

et al. 2020

JAMA Surg

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Identification of the tumor margin during surgery is important for precise minimal resection of lung tumors. Intravenous injection of indocyanine green (ICG) has several limitations when used for intraoperative visualization of lung cancer.OBJECTIVES To describe a technique for intraoperative visualization of lung tumor margin using ICG inhalation and evaluate the clinical applicability of the technique in mouse and rabbit lung tumor models as well as lung specimens of patients with lung tumors. DESIGN, SETTING, AND PARTICIPANTSIn lung tumor models of both mice and rabbits, the distribution of inhaled ICG in the lung tumor margin was investigated in vivo and ex vivo using a near-infrared imaging system. Lung tumor margin detection via inhalation of ICG was evaluated by comparing the results obtained with those of the intravenous injection method (n = 32, each time point for 4 mice). Based on preclinical data, use of ICG inhalation to help detect the tumor margin in patients with lung cancer was also evaluated (n = 6). This diagnostic study was conducted from May 31, 2017, to March 30, 2019. MAIN OUTCOMES AND MEASURESThe use of tumor margin detection by inhaled ICG was evaluated by comparing the inhaled formulation with intravenous administration of ICG. RESULTSFrom 10 minutes after inhalation of ICG to 24 hours, the distribution of ICG in the lungs was significantly higher than that in other organs (signal to noise ratio in the lungs: 39 486.4; interquartile range [IQR], 36 983.74-43 592.5). Ex vivo and histologic analysis showed that, in both lung tumor models, inhaled ICG was observed throughout the healthy lung tissue but was rarely found in tumor tissue. The difference in the fluorescent signal between healthy and tumor lung tissues was associated with the mechanical airway obstruction caused by the tumor and with alveolar macrophage uptake of the inhaled ICG in healthy tissues. Inhalation at a 20-fold lower dose of ICG had a 2-fold higher efficiency for tumor margin detection than did the intravenous injection (2.9; IQR, 2.7-3.2; P < .001). CONCLUSIONS AND RELEVANCEThe results of this study suggest that lung-specific inhalation delivery of ICG is feasible and may be useful for the intraoperative visualization of lung tumor margin in clinical practice.

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“…This is in comparison to the “second window” use of ICG, where larger amounts of the dye (5 mg/kg) are administered intravenously and imaged after 24 h. This approach has been useful for delineating a number of tumors including tumors in the pancreas [ 41 ], lung [ 41 , 42 ], brain [ 43 , 44 ], and prostate [ 45 ]. High dose ICG labeling was reported as feasible in one case report of a patient with pulmonary CRC metastasis, but this approach has not been used for direct labeling of CRC [ 46 ].…”

Section: Non-targeted Fluorescence Agentsmentioning

confidence: 99%

Fluorescence Molecular Targeting of Colon Cancer to Visualize the Invisible

Lwin

Turner

Amirfakhri

et al. 2022

Cells

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Colorectal cancer (CRC) is a common cause of cancer and cancer-related death. Surgery is the only curative modality. Fluorescence-enhanced visualization of CRC with targeted fluorescent probes that can delineate boundaries and target tumor-specific biomarkers can increase rates of curative resection. Approaches to enhancing visualization of the tumor-to-normal tissue interface are active areas of investigation. Nonspecific dyes are the most-used approach, but tumor-specific targeting agents are progressing in clinical trials. The present narrative review describes the principles of fluorescence targeting of CRC for diagnosis and fluorescence-guided surgery with molecular biomarkers for preclinical or clinical evaluation.

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Intraoperative near-infrared imaging can identify sub-centimeter colorectal cancer lung metastases during pulmonary metastasectomy

Cited by 7 publications

References 22 publications

Molecular imaging can identify the location to perform a frozen biopsy during intraoperative frozen section consultation

Molecular imaging can identify the location to perform a frozen biopsy during intraoperative frozen section consultation

Evaluation of Intraoperative Near-Infrared Fluorescence Visualization of the Lung Tumor Margin With Indocyanine Green Inhalation

Fluorescence Molecular Targeting of Colon Cancer to Visualize the Invisible

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