Fundamentals and developments in fluorescence-guided cancer surgery

Mieog, J. Sven D.; Achterberg, Friso B.; Zlitni, Aimen; Hutteman, Merlijn; Burggraaf, Jacobus; Swijnenburg, Rutger-Jan; Gioux, Sylvain; Vahrmeijer, Alexander L.

doi:10.1038/s41571-021-00548-3

Cited by 202 publications

(149 citation statements)

References 165 publications

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“…Advances in intraoperative nodal diagnosis are also expected. Indeed, recent studies have attempted to detect tumor antigens, enzymes produced by tumors, or stromal reactions surrounding metastases using fluorescence observation for rapid intraoperative diagnosis of metastasis (134)(135)(136)(137)(138)(139)(140).…”

Section: Current State and Future Developments In The Evaluation Of Lymph Node Metastasis In Gastric Cancermentioning

confidence: 99%

Significance of Lymph Node Metastasis in the Treatment of Gastric Cancer and Current Challenges in Determining the Extent of Metastasis

2022

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The stomach exhibits abundant lymphatic flow, and metastasis to lymph nodes is common. In the case of gastric cancer, there is a regularity to the spread of lymph node metastasis, and it does not easily metastasize outside the regional nodes. Furthermore, when its extent is limited, nodal metastasis of gastric cancer can be cured by appropriate lymph node dissection. Therefore, identifying and determining the extent of lymph node metastasis is important for ensuring accurate diagnosis and appropriate surgical treatment in patients with gastric cancer. However, precise detection of lymph node metastasis remains difficult. Most nodal metastases in gastric cancer are microscopic metastases, which often occur in small-sized lymph nodes, and are thus difficult to diagnose both preoperatively and intraoperatively. Preoperative nodal diagnoses are mainly made using computed tomography, although the specificity of this method is low because it is mainly based on the size of the lymph node. Furthermore, peripheral nodal metastases cannot be palpated intraoperatively, nodal harvesting of resected specimens remains difficult, and the number of lymph nodes detected vary greatly depending on the skill of the technician. Based on these findings, gastrectomy with prophylactic lymph node dissection is considered the standard surgical procedure for gastric cancer. In contrast, several groups have examined the value of sentinel node biopsy for accurately evaluating nodal metastasis in patients with early gastric cancer, reporting high sensitivity and accuracy. Sentinel node biopsy is also important for individualizing and optimizing the extent of uniform prophylactic lymph node dissection and determining whether patients are indicated for function-preserving curative gastrectomy, which is superior in preventing post-gastrectomy symptoms and maintaining dietary habits. Notably, advancements in surgical treatment for early gastric cancer are expected to result in individualized surgical strategies with sentinel node biopsy. Chemotherapy for advanced gastric cancer has also progressed, and conversion gastrectomy can now be performed after downstaging, even in cases previously regarded as inoperable. In this review, we discuss the importance of determining lymph node metastasis in the treatment of gastric cancer, the associated difficulties, and the need to investigate strategies that can improve the diagnosis of lymph node metastasis.

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Section: Current State and Future Developments In The Evaluation Of Lymph Node Metastasis In Gastric Cancermentioning

confidence: 99%

Significance of Lymph Node Metastasis in the Treatment of Gastric Cancer and Current Challenges in Determining the Extent of Metastasis

2022

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“…There are several other targets showing great promise in fluorescence labeling including antibodies to TAG 72 [ 61 ], other CEACAMs [ 62 ], VEGF [ 63 ], and mucins, as well as several different delivery vehicles (e.g., nanobody [ 64 ], small particles [ 65 ]) and different labels (e.g., quantum dots [ 64 ]). Excellent reviews have already been done on these topics [ 1 , 2 , 58 , 59 , 66 ]. Given the absence of published head-to-head trials, no method is widely accepted as superior to the other.…”

Section: Discussionmentioning

confidence: 99%

“…Surgical resection remains a cornerstone of treatment for solid organ tumors. To achieve complete (R0) resection, the surgeon relies upon tactile and visual cues, preoperative imaging and his or her own experience [ 1 , 2 ]. The presence or absence of metastatic disease is critical in determining appropriate surgical treatment.…”

Section: Introductionmentioning

confidence: 99%

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The Use of Fluorescent Anti-CEA Antibodies to Label, Resect and Treat Cancers: A Review

et al. 2021

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A major barrier to the diagnosis and effective treatment of solid-tumor cancers is the difficulty in detection and visualization of tumor margins in primary and metastatic disease. The use of fluorescence can augment the surgeon’s ability to detect cancer and aid in its resection. Several cancer types express carcinoembryonic antigen (CEA) including colorectal, pancreatic and gastric cancer. Antibodies to CEA have been developed and tagged with near-infrared fluorescent dyes. This review article surveyed the use of CEA antibodies conjugated to fluorescent probes for in vivo studies since 1990. PubMed and Google Scholar databases were queried, and 900 titles and abstracts were screened. Fifty-nine entries were identified as possibly meeting inclusion/exclusion criteria and were reviewed in full. Forty articles were included in the review and their citations were screened for additional entries. A total of 44 articles were included in the final review. The use of fluorescent anti-CEA antibodies has been shown to improve detection and resection of tumors in both murine models and clinically. The cumulative results indicate that fluorescent-conjugated anti-CEA antibodies have important potential to improve cancer diagnosis and surgery. In an emerging technology, anti-CEA fluorescent antibodies have also been successfully used for photoimmunotherapy treatment for cancer.

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“…However, the complex and heterogeneous tumor characteristics of PDAC with its extensive desmoplastic reaction and locoregional changes resulting from NT as well as its retroperitoneally anatomical location make this very challenging [ 31 ]. Near-infrared fluorescence (NIRF) imaging, also called fluorescence-guided surgery (FGS), a novel technique, can offer a solution by providing real-time intraoperative guidance by enhancing visual contrast for localization of the tumor and discrimination between malignant and benign tissue [ 40 , 41 ]. FGS uses a fluorescent dye conjugated to a molecular tracer designed to bind specific molecular features on (tumor)-target cells (i.e., tumor tissue, tumor stroma, etc.)…”

Section: Introductionmentioning

confidence: 99%

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

Dam

Vuijk

Stibbe

et al. 2021

Cancers

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Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient’s treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.

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Fundamentals and developments in fluorescence-guided cancer surgery

Cited by 202 publications

References 165 publications

Significance of Lymph Node Metastasis in the Treatment of Gastric Cancer and Current Challenges in Determining the Extent of Metastasis

Significance of Lymph Node Metastasis in the Treatment of Gastric Cancer and Current Challenges in Determining the Extent of Metastasis

The Use of Fluorescent Anti-CEA Antibodies to Label, Resect and Treat Cancers: A Review

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

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