Search Results (35)

Head and neck squamous cell carcinomas (HNSCCs) are the seventh most common form of cancer worldwide, typically characterized by high mortality and significant morbidity, including pain and speech and swallowing disorders. Complete tumor tissue resection, the common first line of therapy, remains a surgical challenge with room for improvements. Because tumor cells express highly specific surface molecules serving as receptors for ligands, specific targeting ligands can be conjugated to fluorescent molecules in order to better visualize tumor borders. Targeted fluorescence-guided surgery (T-FGS) as well as tumor-targeted and near-infrared (NIR) fluorescence imaging are emerging techniques for real-time intraoperative cancer imaging. Targeting agents include nanodots or fluorophores, which have been conjugated to specific ligands like antibodies, peptides, or other synthetic moieties. This article surveys tumor-targeted ligands in recent and current preclinical studies and clinical trials related to HNSCC, highlighting common NIRF dyes used for molecular imaging and their physical properties, working concentrations, and associated risks. Smaller ligands, nanodots, dual-modality NIR dyes, and activatable agents can enhance tumor-targeting processes, resulting in faster, more penetrable, and clearer imaging, which could lead to improved clinical applications and better tumor removal rates in the future. Full article

Maximal safe surgical resection remains a critical component of glioblastoma (GBM) management, improving both survival and quality of life. However, complete tumor removal is hindered by the infiltrative nature of GBM and its proximity to eloquent brain regions. Fluorescence-guided surgery (FGS) has emerged as a valuable tool to enhance intraoperative tumor visualization and optimize resection outcomes. Currently used fluorophores such as 5-aminolevulinic acid (5-ALA), fluorescein sodium (FS), and indocyanine green (ICG) have distinct advantages but are limited by suboptimal specificity, shallow tissue penetration, and technical constraints. 5-ALA and SF often yield unreliable signals in low-grade tumors or infiltrative regions and also pose challenges such as phototoxicity and poor depth resolution. In contrast, near-infrared (NIR) fluorescence imaging represents a promising next-generation approach, providing superior tissue penetration, reduced autofluorescence, and real-time delineation of tumor margins. This review explores the mechanisms, clinical applications, and limitations of currently approved FGS agents and highlights future directions in image-guided neurosurgery. Full article

Fluorescence-guided surgery (FGS) was pioneered for glioma and is now established as the standard of care. Gliomas are infiltrative tumours with diffuse margins. FGS provides improved intra-operative identification of tumour margins based on tumour-specific emission visible to the operating surgeon, resulting in increased rates of gross total resection. Multiple fluorescence agents may be used including 5-ALA, fluorescein sodium, and indocyanine green (ICG). This review details the indication, required equipment, mechanism of action, evidence base, limitations, and regulatory issues for each fluorophore as utilised in current clinical practice. FGS for glioma is limited by a reliance on subjective interpretation of visible fluorescence, which is often not present in low-grade glioma (LGG) or at the infiltrative tumour margin. Consequently, there has been a drive to develop enhanced, objective FGS techniques utilising both quantitative fluorescence (QF) imaging systems and novel fluorophores. This review provides an overview of emerging QF imaging systems for FGS. The pipeline for novel fluorophore development is also summarised. Full article

Background/Objectives: Glioblastoma (GBM) is the most common primary malignant central nervous system tumor, accounting for 50.9% of malignant CNS diagnoses and carrying a median survival of 15 months despite maximal standard therapy. High recurrence rates are driven by residual infiltrative tumor cells at the resection margin. Fluorescence-guided surgery (FGS) has emerged as a key innovation to improve intraoperative tumor visualization and maximize the extent of resection (EOR). This review examines the historical development, current clinical applications, and future directions of FGS in GBM surgery. Methods: A comprehensive literature review was conducted, covering the evolution of fluorophores (fluorescein, indocyanine green [ICG], and 5-aminolevulinic acid [5-ALA]), visualization technologies (wide- and narrow-field modalities), therapeutic adjuncts (photodynamic and sonodynamic therapies), and clinical adoption patterns and outcomes. Results: Early intraoperative fluorescence using fluorescein dates to 1947. ICG angiography has broad surgical utility, while 5-ALA received FDA approval in 2017, with phase III trials demonstrating gross total resection rates of 65% versus 36% with white-light surgery. Adjunct technologies—3D exoscopes, FGS-compatible loupes, and quantitative spectroscopy probes—enhance detection of residual tumor. Preliminary studies of intraoperative photodynamic and sonodynamic therapies show feasibility and potential survival benefits. Global adoption of 5-ALA FGS exceeds 75% among surveyed neurosurgeons. Conclusions: FGS significantly improves EOR in GBM surgery, translating into better patient outcomes. Ongoing clinical trials and technological refinements—novel fluorophores, quantitative imaging, and therapeutic applications—promise to further optimize tumor visualization and treatment. Full article

Background/Objectives: Targeted and non-targeted fluorescent molecular probes (FMPs) can be used intra-operatively to visualise tumour tissue. Multiple probes have been clinically approved for fluorescence-guided surgery (FGS) in adult oncology, and the translation of these technologies to paediatric neuroblastoma may provide novel strategies for optimising tumour resection whilst minimising morbidity. We aimed to identify clinically approved FMPs with potential utility for FGS in neuroblastoma. Methods: A systematic review of the literature was performed in accordance with the PRISMA guidelines (PROSPERO CRD42024541623). PubMed and Web of Science databases were searched to identify studies investigating clinically approved FGS probes and/or their targets in the context of neuroblastoma. Pre-clinical and clinical studies looking at human neuroblastoma were included. The primary outcomes were that the FGS probe was tested in patients with neuroblastoma, the probe selectively accumulated in neuroblastoma tissue, or that the target of the probe was selectively over-expressed in neuroblastoma tissue. Results: Forty-two studies were included. Four were clinical studies, and the remainder were pre-clinical studies using human neuroblastoma cell lines, human tumour tissue, or xenograft models using human neuroblastoma cells. The only FMP clinically evaluated in neuroblastoma is indocyanine green (ICG). FMP targets that have been investigated in neuroblastoma include poly-ADP ribose polymerase (PARP) (targeted by PARPiFL), endothelial growth factor receptor (EGFR) (targeted by Panitumumab-IRDye800CW, Cetuximab-IRDye800CW, Nimotuzumab-IRDye800CW and QRHKPRE-Cy5), vascular endothelial growth factor receptor (VEGFR) (targeted by Bevacizumab IRDye800CW), and proteases such as cathepsins and matrix metalloproteinases that activate the fluorescent signal of FMPs, such as LUM015 and AVB-620. Of the clinical studies included, all were found to have a high risk of bias. Conclusions: ICG is the only clinically approved fluorescent dye currently used for FGS in neuroblastoma; however, studies suggest that its ability to recognise neuroblastoma tissue is inconsistent. There are several clinically approved FMPs, or FMPs in clinical trials, that are used in adult oncology surgery that have targets expressed in neuroblastoma. Further research should validate these probes in neuroblastoma to enable their rapid translation into clinical practice. Full article

Maximal safe surgical resection is the gold standard in brain tumor surgery. Fluorescence-guided surgery (FGS) is one of many intraoperative techniques that have been designed with the intention of accomplishing this goal. 5-aminolevulinic acid (5-ALA) is one of the main fluorophores that facilitates FGS in neurosurgical oncology. Multiple different types of brain tumors can take in and metabolize 5-ALA into protoporphyrin IX (PpIX) through the mitochondria heme biosynthesis pathway. PpIX then selectively accumulates in brain tumor cells due to decreased ferrochelatase activity and emits red fluorescence (630–720 nm) when excited with blue light (375–440 nm). This mechanism allows neurosurgeons to better visualize tumor burden and increase extent of resection while preserving non-cancerous brain parenchyma and, specifically, eloquent white matter tracts, if combined with mapping techniques, thereby minimizing morbidity while improving survival. While 5-ALA use is well established in the treatment of high-grade gliomas, its applicability in recurrent high-grade and non-enhancing IDH-mutant low-grade gliomas, as well as non-glial tumors, is less established or limited by certain features of their cellular and molecular biology. This review aims to discuss the current landscape of 5-ALA utility across the diverse range of brain tumors, practical considerations that optimize its current use in neurosurgery, modern clinical limitations of 5-ALA, and how its application can be expanded by combining its use with other techniques that overcome current limitations. Full article

Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye with unique photoluminescent properties, is a helpful tool in many medical applications. ICG produces fluorescence when excited by NIR light, enabling accurate tissue visualization and real-time imaging. This study investigates the fundamental processes behind ICG’s photoluminescence as well as its present and possible applications in treatments and medical diagnostics. Fluorescence-guided surgery (FGS) has been transformed by ICG’s capacity to visualize tumors, highlight blood flow, and facilitate lymphatic mapping, all of which have improved surgical accuracy and patient outcomes. Furthermore, the fluorescence of the dye is being studied for new therapeutic approaches, like photothermal therapy, in which NIR light can activate ICG to target and destroy cancer cells. We go over the benefits and drawbacks of ICG’s photoluminescent qualities in therapeutic contexts, as well as current studies that focus on improving its effectiveness, security, and adaptability. More precise disease detection, real-time monitoring, and tailored therapy options across a variety of medical specialties are made possible by the ongoing advancement of ICG-based imaging methods and therapies. In the main part of our work, we strive to take into account the latest reports; therefore, we used clinical articles going back to 2020. However, for the sake of the theoretical part, the oldest article used by us is from 1995. Full article

Fluorescence-guided surgery (FGS) is an innovative technique for accurately localizing tumors during surgery, particularly valuable in brain tumor detection. FGS uses advanced spectral and imaging tools to provide precise, quantitative fluorescence measurements that enhance surgical accuracy. However, the current challenge with these advanced tools lies in their lack of miniaturization, which limits their practicality in complex surgical environments. In this study, we present a miniaturized fluorescence detection system, developed using state-of-the-art CMOS color sensors, to overcome this challenge and improve brain tumor localization. Our 3.1 × 3 mm multispectral sensor platform measures fluorescence intensity ratios at 635 nm and 514 nm, producing a high-resolution fluorescence distribution map for a 16 mm × 16 mm area. This device shows a high correlation (R2 > 0.98) with standard benchtop spectrometers, confirming its accuracy for real-time, on-chip fluorescence detection. With its compact size, our system has strong potential for integration with existing handheld surgical tools, aiming to improve outcomes in tumor resection and enhance intraoperative tumor visualization. Full article

Background: The objective in epithelial ovarian cancer is to reach maximal cytoreduction with no visible residual tumor. Tumor detection during cytoreductive surgery depends on visual inspection, palpation, or blind biopsy, methods that lack reliability for identifying microscopic disease. Although the importance of microscopic disease in epithelial ovarian cancer is controversial, it may harbor chemoresistant cells and explain the high recurrence rates. Fluorescence-guided surgery (FGS) is an emerging approach. However, the potential in ovarian cancer remains underexplored; the majority of the existing evidence pertains to gastrointestinal tumors and a limited group of ovarian cancer patients. Their comparative effectiveness is still uncertain. Objective: To systematically review and evaluate the role of fluorescence-guided surgical techniques in detecting microscopic disease in ovarian cancer and compare their efficacy to total peritonectomy. Data Sources: A systematic search was made in three databases (PubMed, Web of Science, and Embase). The search was conducted from 1975 to 2024, including randomized controlled trials, observational studies, and conference abstracts in the last 25 years. Study Selection: Clinical studies published in English involving ovarian cancer patients undergoing FGS or total peritonectomy were included. Case reports, reviews, animal studies, and studies involving mixed cancer populations without ovarian cancer-specific data were excluded. Two independent reviewers screened 631 studies, yielding 12 eligible studies for final analysis. Data Extraction and Synthesis: Data were extracted and synthesized in accordance with PRISMA and MOOSE guidelines, using random-effects models for independent analysis. Sensitivity, specificity, positive predictive value (PPV), and odds ratios (ORs) were grouped, accompanied by subgroup analyses based on the fluorescence agent employed. For quality assessment, we utilized the NIH quality tool. Main Outcome(s) and Measure(s): The primary outcome was the rate of change in surgical management due to fluorescence guidance or total peritonectomy. Secondary outcomes comprised lesion-level sensitivity, specificity, and PPV. Safety outcomes included adverse events associated with fluorescence agents. Results: There were 12 studies involving 429 ovarian cancer patients. FGS improved the detection of microscopic disease compared to standard visualization methods, with a pooled sensitivity of 0.77. Folate receptor-targeted agents had high sensitivity (84%) but low specificity (26%). Aminolevulinic acid (5-ALA) showed superior diagnostic accuracy with a sensitivity of 84% and a specificity of 96%. Total peritonectomy showed no significant advantage over FGS for detecting microscopic disease. The adverse events were mild, with no serious events reported. We observed a high heterogeneity across studies and methodologies. Conclusions and Relevance: Fluorescence-guided surgery utilizing fluorescence tracers demonstrates potential in improving the detection of microscopic disease and may change surgical management in epithelial ovarian cancer, particularly with 5-ALA. Variability in performance and limited data on survival outcomes necessitates additional research. Total peritonectomy does not offer further advantage in the detection of microscopic disease. Future trials should focus on standardizing methodology and evaluating the effects of microscopic disease removal on survival outcomes. Registration: The study was registered to PROSPERO as CRD42024578274. Full article

Glioblastoma (GB) is among the most aggressive and difficult-to-treat brain tumors, with a median survival of only 12–15 months despite maximal treatments, including surgery, radiotherapy, and chemotherapy. Extensive surgical resection improves survival in glioblastoma patients; however, achieving complete resection is often hindered by limitations in neurosurgical guidance technologies for accurate tumor margin detection. Recent advancements in fluorescence-guided surgery (FGS) and imaging techniques have significantly enhanced the precision and extent of glioblastoma resections. This study evaluates the impact of NIR fluorescence imaging on tumor visualization, surgical precision, cost-effectiveness, and patient survival. A systematic review of PubMed, Scopus, Google Scholar, and Embase was conducted to identify studies on the role of NIR fluorescence in glioblastoma surgery. A total of 135 studies were included, comprising 10 reviews, three clinical studies, 10 randomized controlled trials (RCTs), 10 preclinical studies, and four case reports, all focused on NIR fluorescence imaging in glioblastoma surgery. The findings indicate that NIR fluorescence imaging significantly improves tumor visualization, resulting in an 18–22% increase in gross total resection (GTR) rates in clinical studies. NIR fluorescence provides continuous real-time feedback, minimizing repeat imaging, reducing operational costs, and increasing GTR. These improvements contribute to better patient outcomes, including extended progression-free survival, improved overall survival, and reduced postoperative neurological deficits. This review underscores the potential of NIR imaging to establish a new standard for intraoperative glioblastoma management. Full article

Background: Surgical resection for pancreatic ductal adenocarcinoma (PDAC) entails the excision of the primary tumour and regional lymphadenectomy. This traditional strategy is challenged by the high rate of early recurrence, suggesting inadequate disease staging. Novel methods of intra-operative staging are needed to allow surgical resection to be tailored to the disease’s biology. Methods: A search of published articles on the PubMed and Embase databases was performed using the terms ‘pancreas’ OR ‘pancreatic’ AND ‘intra-operative staging/detection’ OR ‘guided surgery’. Articles published between January 2000 and June 2023 were included. Technologies that offered intra-operative staging and tailored treatment were curated and summarised in the following integrative review. Results: lymph node (LN) mapping and radioimmunoguided surgery have shown promising results but lacked practicality to facilitate real-time intra-operative staging for PDAC. Fluorescence-guided surgery (FGS) offers high contrast and sensitivity, enabling the identification of cancerous tissue and positive LNs with improved precision following intravenous administration of a fluorescent agent. The unique properties of optical coherence tomography and ultrasound elastography lend themselves to be platforms for virtual biopsy intra-operatively. Conclusions: Accurate intra-operative staging of PDAC, localisation of metastatic LNs, and identification of extra-pancreatic disease remain clinically unmet needs under current detection methods and staging standards. Tumour-specific FGS combined with other diagnostic and therapeutic modalities could improve tumour detection and staging in patients with PDAC. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Currently, surgical resection is the only potentially curative treatment. Unfortunately, less than 20% of PDAC patients are eligible for surgical resection at diagnosis. In the past few decades, neoadjuvant chemotherapy treatment (NCT) has been investigated as a way to downstage PDAC tumors for surgical resection. Fluorescence-guided surgery (FGS) is a technique that can aid in increasing complete resection rates by enhancing the tumor through passive or active targeting of a contrast agent. In active targeting, a probe (e.g., antibody) binds a protein differentially upregulated in the tumor compared to normal tissue. Mucin 16 (MUC16), a transmembrane glycoprotein, has recently been explored as an FGS target in preclinical tumor models. However, the impact of chemotherapy on MUC16 expression is unknown. Methods: To investigate this issue, immunohistochemistry was performed on PDAC patient samples. Results: We found that MUC16 expression was retained after NCT in patient samples (mean expression = 5.7) with minimal change in expression between the matched diagnostic (mean expression = 3.66) and PDAC NCT patient samples (mean expression = 4.5). Conclusions: This study suggests that MUC16 is a promising target for FGS and other targeted therapies in PDAC patients treated with NCT. Full article

This study aims to review the status of the clinical use of monoclonal antibodies (mAbs) that have completed or are in ongoing clinical trials for targeted fluorescence-guided surgery (T-FGS) for the intraoperative identification of the tumor margins of extra-hematological solid tumors. For each of them, the targeted antigen, the mAb generic/commercial name and format, and clinical indications are presented, together with utility, doses, and the timing of administration. Based on the current scientific evidence in humans, the top three mAbs that could be prepared in a GMP-compliant bank ready to be delivered for surgical purposes are proposed to speed up the translation to the operating room and produce a few readily available “off-the-shelf” injectable fluorescent probes for safer and more effective solid tumor resection. Full article

Introduction: There are scarce papers about the use of fluorescence-guided surgery (FGS) in the open surgical field. This study aimed to assess the usefulness of FGS in an open setting in the pediatric population and to report our preliminary experience using the Rubina^® Lens system. Methods: All patients undergoing ICG fluorescence-assisted open surgery over the period September 2022–September 2023 were enrolled. Each surgical procedure was performed using the Rubina^® Lens for ICG fluorescence visualization. Results: A total of 25 patients, 14 boys and 11 girls with a median age at surgery of 5.8 years-old (range 0–15), were enrolled. Surgical indications were dermoid/epidermoid cysts of the head (n = 7), lymphangiomas of the head/neck (n = 2), thyroglossal duct cysts (n = 7), gynecomastia (n = 3), preauricular fistula (n = 2), second branchial cleft fistula (n = 1), fibrolipoma of the shoulder (n = 1) and myofibroma of the gluteal/perineal region (n = 2). In all procedures, an intralesional injection of 2.5 mg/mL ICG solution using a 30-gauge needle was administered. No adverse reactions to ICG occurred. Median operative time was 68.6 min (range 35–189). The visualization of ICG-NIRF with the Rubina^® Lens was achieved in all cases. No intraoperative complications were reported. Postoperative complications occurred in 3/25 patients (12%), with gynecomastia (n = 1), thyroglossal duct cyst (n = 1) and neck lymphangioma (n = 1), who developed a fluid collection in the surgical site, requiring needle aspiration in outpatient care (Clavien–Dindo 2). Complete mass excision was confirmed with pathology reports. Conclusions: Based on this initial experience, FGS using the Rubina^® Lens was very helpful in open surgery, providing enhanced visualization of anatomy and identification of margins, real-time reliability and low complication rate. It was easy to use, time saving, feasible and clinically safe. Previous experience in MIS is necessary to adopt this technology. The accuracy of the injection phase is important to avoid diffusion of the ICG into the perilesional tissue. Full article

Fluorescence-guided surgery (FGS), based on fluorescent tracers binding to tumor-specific biomarkers, could assist surgeons to achieve complete tumor resections. This study evaluated potential biomarkers for FGS in pediatric Ewing sarcoma (ES). Immunohistochemistry (IHC) was performed to assess CD99, CXCR4, CD117, NPY-R-Y1, and IGF-1R expression in ES biopsies and resection specimens. LINGO-1 and GD2 evaluation did not work on the acquired tissue. Based on the immunoreactive scores, anti-CD99 and anti-CD117 were evaluated for binding specificity using flow cytometry and immunofluorescence microscopy. Anti-GD2, a tracer in the developmental phase, was also tested. These three tracers were topically applied to a freshly resected ES tumor and adjacent healthy tissue. IHC demonstrated moderate/strong CD99 and CD117 expression in ES tumor samples, while adjacent healthy tissue had limited expression. Flow cytometry and immunofluorescence microscopy confirmed high CD99 expression, along with low/moderate CD117 and low GD2 expression, in ES cell lines. Topical anti-CD99 and anti-GD2 application on ES tumor showed fluorescence, while anti-CD117 did not show fluorescence for this patient. In conclusion, CD99-targeting tracers hold promise for FGS of ES. CD117 and GD2 tracers could be potential alternatives. The next step towards development of ES-specific FGS tracers could be ex vivo topical application experiments on a large cohort of ES patients. Full article