Consensus Statement on the Use of Near-Infrared Fluorescence Imaging during Pancreatic Cancer Surgery Based on a Delphi Study: Surgeons’ Perspectives on Current Use and Future Recommendations

Abstract

Indocyanine green (ICG) is one of the only clinically approved near-infrared (NIR) fluorophores used during fluorescence-guided surgery (FGS), but it lacks tumor specificity for pancreatic ductal adenocarcinoma (PDAC). Several tumor-targeted fluorescent probes have been evaluated in PDAC patients, yet no uniformity or consensus exists among the surgical community on the current and future needs of FGS during PDAC surgery. In this first-published consensus report on FGS for PDAC, expert opinions were gathered on current use and future recommendations from surgeons’ perspectives. A Delphi survey was conducted among international FGS experts via Google Forms. Experts were asked to anonymously vote on 76 statements, with ≥70% agreement considered consensus and ≥80% participation/statement considered vote robustness. Consensus was reached for 61/76 statements. All statements were considered robust. All experts agreed that FGS is safe with few drawbacks during PDAC surgery, but that it should not yet be implemented routinely for tumor identification due to a lack of PDAC-specific NIR tracers and insufficient evidence proving FGS’s benefit over standard methods. However, aside from tumor imaging, surgeons suggest they would benefit from visualizing vasculature and surrounding anatomy with ICG during PDAC surgery. Future research could also benefit from identifying neuroendocrine tumors. More research focusing on standardization and combining tumor identification and vital-structure imaging would greatly improve FGS’s use during PDAC surgery.

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“…Der Einsatz von gezielten Kontrastmitteln (z. B. antikörpergebunden) kann eine höhere Spezifität für bestimmte Strukturen oder pathologische Zustände bedeuten [37]. Fluoreszenzfarbstoffe haben die Eigenschaft, größtenteils vaskulär proteingebunden zu migrieren und somit Perfusion anzuzeigen [38,39,40].…”

Global trends in the application of fluorescence imaging in pancreatic diseases: a bibliometric and knowledge graph analysis

“…Despite some limitations in its application to pancreatic diseases, ICG still possesses tremendous potential for development. Future research should focus on leveraging ICG’s characteristics to develop targeted probes ( 31 ). By combining ICG with artificially synthesized antibodies against tumor markers, we can enhance the probe’s fluorescence development efficiency and targeting accuracy while ensuring good biocompatibility.…”

“…II. Problems with ICG application dose: In liver tumors, the injection dose of ICG is usually 0.25-0.50 g/kg, while in pancreatic tumors, it is 2-5 mg/kg ( 31 ). However, excessive doses may lead to serious complications such as anaphylaxis.…”

Near-Infrared Fluorescence Imaging of Pancreatic Cancer Using a Fluorescently Labelled Anti-CEA Nanobody Probe: A Preclinical Study

“…During surgery, margin assessment is of utmost importance since tumor-positive resection margins are encountered in up to 70% of the cases [ 4 , 5 ]. Distinguishing tumor tissue from benign surrounding tissues using an imaging technique that is easy to use, such as NIR fluorescence imaging, is one of the key elements to improve the quality of pancreatic surgery [ 6 ] of the most commonly targeted and studied biomarkers for pancreatic cancer is the carcinoembryonic antigen (CEA), which is a glycoprotein involved in cell adhesion and is overexpressed in more than 90% of pancreatic cancers [ 7 , 8 , 9 ]. CEA is still overexpressed in tumor tissue after neoadjuvant therapy, which makes this an excellent target moiety, and therefore an interesting candidate for targeted fluorescence imaging, since more patients are being treated with neoadjuvant therapy followed by surgery and/or adjuvant chemotherapy [ 10 ].…”