# Fluorescence-Guided Surgery in Colorectal Cancer: State-of-the-Art and Translational Perspectives

**Authors:** Florin-Alexandru Ruse, Dumitru-Cristinel Badiu, Cristian-Gabriel Popescu, Andreea-Ramona Treteanu, Anca Zgura, Octavian Andronic

PMC · DOI: 10.3390/curroncol33030160 · 2026-03-11

## TL;DR

This review explores how fluorescence-guided surgery improves colorectal cancer operations, focusing on current uses and future needs for wider adoption.

## Contribution

The paper provides a comprehensive review linking clinical maturity to translational steps needed for routine adoption of fluorescence-guided surgery in colorectal cancer.

## Key findings

- ICG fluorescence angiography improves anastomotic perfusion assessment but its effect on leak prevention is protocol-dependent.
- ICG improves lymphatic mapping but cannot reliably distinguish benign from metastatic nodes.
- Targeted probes and multimodal approaches show promise for detecting peritoneal and hepatic metastases.

## Abstract

Fluorescence-guided surgery is increasingly used in colorectal cancer to improve real-time intraoperative visualization. Near-infrared imaging with indocyanine green is already applied to assess anastomotic perfusion and map lymphatic drainage, while newer tumor-targeted tracers are being developed for lesion identification, margin assessment, and detection of peritoneal and hepatic metastases. This review summarizes current evidence across these applications and highlights the main barriers to wider adoption, particularly protocol standardization, objective fluorescence quantification, and validation of targeted probes.

Background: Fluorescence-guided surgery based on near-infrared imaging, most often using indocyanine green (ICG), is increasingly used in colorectal cancer (CRC) surgery. This narrative review integrates current evidence across four clinically relevant domains-anastomotic perfusion, lymphatic mapping, tumor localization, and metastasis detection and emphasizes the technical and translational factors that will determine broader implementation. Methods: We performed a structured narrative review of clinical and translational studies identified through PubMed and citation tracking, with emphasis on ICG-based workflows and emerging targeted tracers. Because the literature spans heterogeneous interventions, imaging platforms, and endpoints, no de novo meta-analysis or formal risk-of-bias assessment was undertaken. Results: ICG fluorescence angiography is the most mature application and can refine transection-line selection, although its effect on anastomotic leak appears protocol dependent. In lymphatic mapping, ICG improves visualization of drainage pathways and nodal basins but does not reliably distinguish benign from metastatic nodes. For tumor localization, ICG supports lesion marking and dynamic tissue characterization, while targeted probes and contrast-free adjuncts may improve oncologic specificity. For metastatic disease, ICG is most useful for liver margin guidance and for excluding residual disease, whereas CEA-targeted and multimodal approaches appear particularly promising for peritoneal metastases. Conclusions: The added value of this review lies in linking current clinical maturity to the translational steps still required for routine adoption. In CRC surgery, fluorescence imaging is already useful in selected settings, but broader implementation will depend on standardized protocols, objective real-time quantification, and multicenter validation of targeted tracers against clinically meaningful outcomes.

## Linked entities

- **Chemicals:** indocyanine green (PubChem CID 5282412), ICG (PubChem CID 5282412)
- **Diseases:** colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** CD68 (CD68 molecule) [NCBI Gene 968] {aka GP110, LAMP4, SCARD1}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, MET (MET proto-oncogene, receptor tyrosine kinase) [NCBI Gene 4233] {aka AUTS9, DA11, DFNB97, HGFR, RCCP2, c-Met}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CTSS (cathepsin S) [NCBI Gene 1520]
- **Diseases:** hepatic metastasis (MESH:D009362), intestinal (MESH:D007410), polyps (MESH:D011127), retroperitoneal lymphadenopathy (MESH:D012186), thyroid hyperfunction (MESH:C566386), T3-T4 cancers (MESH:D009369), weight loss (MESH:D015431), carcinogenesis (MESH:D063646), colorectal peritoneal (MESH:D010538), PCI (MESH:D010534), T4 (MESH:D005067), injury to (MESH:D014947), hepatic (MESH:D056486), Colorectal cancer (MESH:D015179), AL (MESH:D057868), ischemia (MESH:D007511), diabetes mellitus (MESH:D003920), T3 (MESH:C537047), oncologic (MESH:D000072716), inflammation (MESH:D007249), hypersensitivity (MESH:D004342), leak (MESH:D019559), benign lesions (MESH:D001932), toxicity (MESH:D064420), cardiovascular disease (MESH:D002318), MSI-H (MESH:D000848), hepatic or renal impairment (MESH:D008107), mucosal injury (MESH:D052016), PALN metastases (MESH:D008207), intestinal polyposis (MESH:D044483), rectal cancer (MESH:D012004), dysplasia (MESH:D015792)
- **Chemicals:** sotorasib (MESH:C000706028), Atezolizumab (MESH:C000594389), IRDye800CW (MESH:C562366), iodine (MESH:D007455), xenon (MESH:D014978), EMI- (-), FA (MESH:D005492), ICG (MESH:D007208), Se (MESH:D012643), AOM (MESH:D001397), Panitumumab (MESH:D000077544)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** G12C
- **Cell lines:** Colo205 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0218), LS174T — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_1384), SW948 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0632), Balb/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), HT-29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), RKO — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0504), HCT8 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_2478)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC13024970/full.md

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Source: https://tomesphere.com/paper/PMC13024970