Fluorescence-guided surgery for hepatocellular carcinoma: From clinical practice to laboratories

Introduction

Hepatocellular carcinoma (HCC) is a major global health issue, with significant morbidity and mortality rates. As the sixth most common cancer and the third leading cause of cancer-related deaths, HCC poses substantial treatment challenges. Effective management often involves hepatectomy, where the precise identification and complete removal of tumor lesions are critical for achieving a favorable prognosis. However, limitations exist in traditional imaging techniques, which often fail to provide real-time guidance during surgery. This has spurred the exploration of fluorescence-guided surgery (FGS) as a potential tool for enhancing surgical precision.

Fluorescence-Guided Surgery in HCC

Fluorescence-guided surgery utilizes fluorescent dyes to improve the visualization of tumor tissues during surgery, providing real-time guidance for surgeons. One of the most widely used agents in FGS is indocyanine green (ICG), a near-infrared fluorescent dye. ICG binds to plasma proteins, allowing it to be absorbed by liver cells. Due to the impaired bile excretion function of HCC cells, ICG tends to accumulate in tumor tissues, making them detectable during surgery. Despite its widespread use, ICG has limitations, such as poor specificity for distinguishing malignant from benign tumors and difficulty in visualizing deep lesions.

Advances in Fluorescent Probes

To address the limitations of ICG, recent developments have focused on novel fluorescent probes. These include enzymes, reactive oxygen species (ROS), reactive sulfur species (RSS), and pH-sensitive probes, which show promise for more specific and sensitive detection of HCC. Among these, aggregation-induced emission (AIE) probes represent a significant advancement. AIE probes are unique because they do not emit fluorescence in dilute solutions but exhibit strong fluorescence when aggregated, making them highly effective for real-time surgical navigation. These probes offer several advantages, such as excellent biocompatibility, high photostability, and low background signals, thus overcoming the shortcomings of traditional fluorescent agents.

Clinical Applications and Challenges

ICG-based fluorescence guidance has shown significant success in clinical settings, allowing surgeons to better identify tumor boundaries and detect small, otherwise undetectable, lesions. However, challenges remain in clinical application. For example, ICG is not effective for deep tissue visualization, and its uptake is influenced by factors such as cirrhosis or blood flow, which can complicate its use in different patient populations. Moreover, the fluorescence signal from ICG can be compromised by the presence of benign liver conditions, making it difficult to differentiate between malignant and non-malignant tissues.

Future Directions

The future of FGS in HCC treatment lies in the development of next-generation fluorescent probes with improved characteristics. Research is ongoing to enhance tissue penetration depth and probe specificity, particularly through the development of near-infrared (NIR) fluorophores in the NIR-II region (1,000-1,700 nm). Furthermore, integrating fluorescence imaging with other imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) may offer multimodal approaches to surgery, improving both diagnostic accuracy and surgical outcomes. The ultimate goal is to enable surgeons to achieve more precise resections, reduce recurrence, and improve patient survival rates.

Conclusion

Fluorescence-guided surgery represents a promising advancement in the treatment of HCC. By offering real-time tumor visualization, FGS improves the accuracy of tumor resection, ultimately contributing to better clinical outcomes. As fluorescent probe technology continues to evolve, its application in HCC surgery is expected to become increasingly sophisticated, providing a powerful tool for oncologic surgeons in the battle against liver cancer.

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https://www.xiahepublishing.com/2310-8819/JCTH-2024-00375

The study was recently published in the Journal of Clinical and Translational Hepatology.

The Journal of Clinical and Translational Hepatology (JCTH) is owned by the Second Affiliated Hospital of Chongqing Medical University and published by XIA & HE Publishing Inc. JCTH publishes high quality, peer reviewed studies in the translational and clinical human health sciences of liver diseases. JCTH has established high standards for publication of original research, which are characterized by a study’s novelty, quality, and ethical conduct in the scientific process as well as in the communication of the research findings. Each issue includes articles by leading authorities on topics in hepatology that are germane to the most current challenges in the field. Special features include reports on the latest advances in drug development and technology that are relevant to liver diseases. Regular features of JCTH also include editorials, correspondences and invited commentaries on rapidly progressing areas in hepatology. All articles published by JCTH, both solicited and unsolicited, must pass our rigorous peer review process.

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