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      Intraoperative Multispectral Fluorescence Imaging for the Detection of the Sentinel Lymph Node in Cervical Cancer: A Novel Concept

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          Abstract

          Purpose

          Real-time intraoperative near-infrared fluorescence (NIRF) imaging is a promising technique for lymphatic mapping and sentinel lymph node (SLN) detection. The purpose of this technical feasibility pilot study was to evaluate the applicability of NIRF imaging with indocyanin green (ICG) for the detection of the SLN in cervical cancer.

          Procedures

          In ten patients with early stage cervical cancer, a mixture of patent blue and ICG was injected into the cervix uteri during surgery. Real-time color and fluorescence videos and images were acquired using a custom-made multispectral fluorescence camera system.

          Results

          Real-time fluorescence lymphatic mapping was observed in vivo in six patients; a total of nine SLNs were detected, of which one (11%) contained metastases. Ex vivo fluorescence imaging revealed the remaining fluorescent signal in 11 of 197 non-sentinel LNs (5%), of which one contained metastatic tumor tissue. None of the non-fluorescent LNs contained metastases.

          Conclusions

          We conclude that lymphatic mapping and detection of the SLN in cervical cancer using intraoperative NIRF imaging is technically feasible. However, the technique needs to be refined for full applicability in cervical cancer in terms of sensitivity and specificity.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s11307-010-0425-7) contains supplementary material, which is available to authorized users.

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          Most cited references26

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          Technical details of intraoperative lymphatic mapping for early stage melanoma.

          D Morton, D Wen, J Wong … (1992)
          The initial route of metastases in most patients with melanoma is via the lymphatics to the regional nodes. However, routine lymphadenectomy for patients with clinical stage I melanoma remains controversial because most of these patients do not have nodal metastases, are unlikely to benefit from the operation, and may suffer troublesome postoperative edema of the limbs. A new procedure was developed using vital dyes that permits intraoperative identification of the sentinel lymph node, the lymph node nearest the site of the primary melanoma, on the direct drainage pathway. The most likely site of early metastases, the sentinel node can be removed for immediate intraoperative study to identify clinically occult melanoma cells. We successfully identified the sentinel node(s) in 194 of 237 lymphatic basins and detected metastases in 40 specimens (21%) on examination of routine hematoxylin-eosin-stained slides (12%) or exclusively in immunohistochemically stained preparations (9%). Metastases were present in 47 (18%) of 259 sentinel nodes, while nonsentinel nodes were the sole site of metastasis in only two of 3079 nodes from 194 lymphadenectomy specimens that had an identifiable sentinel node, a false-negative rate of less than 1%. Thus, this technique identifies, with a high degree of accuracy, patients with early stage melanoma who have nodal metastases and are likely to benefit from radical lymphadenectomy.
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            The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping.

            Susan Troyan, Vida Kianzad, Summer Gibbs-Strauss … (2009)
            Invisible NIR fluorescent light can provide high sensitivity, high-resolution, and real-time image-guidance during oncologic surgery, but imaging systems that are presently available do not display this invisible light in the context of surgical anatomy. The FLARE imaging system overcomes this major obstacle. Color video was acquired simultaneously, and in real-time, along with two independent channels of NIR fluorescence. Grayscale NIR fluorescence images were converted to visible "pseudo-colors" and overlaid onto the color video image. Yorkshire pigs weighing 35 kg (n = 5) were used for final preclinical validation of the imaging system. A six-patient pilot study was conducted in women undergoing sentinel lymph node (SLN) mapping for breast cancer. Subjects received (99m)Tc-sulfur colloid lymphoscintigraphy. In addition, 12.5 microg of indocyanine green (ICG) diluted in human serum albumin (HSA) was used as an NIR fluorescent lymphatic tracer. The FLARE system permitted facile positioning in the operating room. NIR light did not change the look of the surgical field. Simultaneous pan-lymphatic and SLN mapping was demonstrated in swine using clinically available NIR fluorophores and the dual NIR capabilities of the system. In the pilot clinical trial, a total of nine SLNs were identified by (99m)Tc- lymphoscintigraphy and nine SLNs were identified by NIR fluorescence, although results differed in two patients. No adverse events were encountered. We describe the successful clinical translation of a new NIR fluorescence imaging system for image-guided oncologic surgery.
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              The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States--a 24-year population-based study.

              Darcey Smith, John M Tiffany, C Qualls … (2000)
              The aim of this study was to compare the age-adjusted incidence and survival for invasive adenocarcinoma and squamous cell carcinoma of the uterine cervix using population-based data. The SEER database was used to identify all cases of cervical cancer registered between 1973 and 1996. Stage was defined as localized, regional, or distant. Age-adjusted incidence rates were analyzed statistically using the Jonchkeere-Terpstra exact test for trends. Relative and observed survival rates, respectively, were compared using z tests and log-rank tests. The age-adjusted incidence rates per 100,000 for all invasive cervical cancers decreased by 36.9% over 24 years [12.35 (1973-1977) vs 7.79 (1993-1996)]. Similarly, the age-adjusted incidence rates for squamous cell carcinoma declined by 41.9% [9.45 (1973-1977) vs 5.49 (1993-1996)]. In contrast, the age-adjusted incidence rates for adenocarcinoma increased by 29.1% [1.34 (1973-1977) vs 1.73 (1993-1996)]. The proportion of adenocarcinoma increased 107.4% relative to all cervical cancer, 95.2% relative to squamous cell carcinoma, and 49.3% relative to the population of women at risk [10. 8% vs 22.4% (P < 0.001), 12.4% vs 24.0% (P < 0.001), and 1.40 vs 2. 09 per 100,000 women (P < 0.001), respectively]. Observed survival rates for adenocarcinoma vs squamous cell carcinoma were poorer for regional (P = 0.04), but not localized or distant disease. Over the past 24 years, the incidence of all cervical cancer and squamous cell carcinoma has continued to decline. However, the proportion of adenocarcinoma relative to squamous cell carcinoma and to all cervical cancers has doubled, and the rate of adenocarcinoma per population at risk has also increased. These results suggest that current screening practices in the United States are insufficient to detect a significant proportion of adenocarcinoma precursor lesions. Copyright 2000 Academic Press.
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                Author and article information

                Contributors
                : +31-50-3612283 , +31-50-3614873 , g.m.van.dam@chir.umcg.nl
                Journal
                Journal ID (nlm-ta): Mol Imaging Biol
                Title: Molecular Imaging and Biology
                Publisher: Springer-Verlag (New York )
                ISSN (Print): 1536-1632
                ISSN (Electronic): 1860-2002
                Publication date (Electronic): 11 September 2010
                Publication date PMC-release: 11 September 2010
                Publication date (Print): October 2011
                Volume: 13
                Issue: 5
                Pages: 1043-1049
                Affiliations
                [1 ]Department of Surgery, University Medical Center Groningen, Groningen, the Netherlands
                [2 ]Department of Surgery, BioOptical Imaging Center Groningen (BICG), University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands
                [3 ]Department of Obstetrics and Gynaecology, University Medical Center Groningen, Groningen, the Netherlands
                [4 ]Technical University Munich and Helmholtz Zentrum Munich, Institute for Biological and Medical Imaging (IBMI), Munich, Germany
                Article
                Publisher ID: 425
                DOI: 10.1007/s11307-010-0425-7
                PMC ID: 3179588
                PubMed ID: 20835767
                SO-VID: 640cc94b-7196-42d9-8592-f234c0d5003b
                Copyright © © The Author(s) 2010
                History
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © World Molecular Imaging Society 2011

                ScienceOpen disciplines: Molecular biology
                Keywords: multispectral intraoperative imaging,cervical cancer,near-infrared fluorescence,sentinel lymph node
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: multispectral intraoperative imaging, cervical cancer, near-infrared fluorescence, sentinel lymph node

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