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      Near-infrared fluorescence imaging for sentinel lymph node identification in colon cancer: a prospective single-center study and systematic review with meta-analysis

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          Abstract

          Background

          Near-infrared (NIR) fluorescence imaging has the potential to overcome the current drawbacks of sentinel lymph node mapping (SLNM) in colon cancer. Our aim was to provide an overview of current SLNM performance and of factors influencing successful sentinel lymph node (SLN) identification using NIR fluorescence imaging in colon cancer.

          Methods

          A systematic review and meta-analysis was conducted to identify currently used methods and results. Additionally, we performed a single-center study using indocyanine green (ICG) as SLNM dye in colon cancer patients scheduled for a laparoscopic colectomy. SLNs were analyzed with conventional hematoxylin-and-eosin staining and additionally with serial sectioning and immunohistochemistry (extended histopathological assessment). A true-positive procedure was defined as a tumor-positive SLN either by conventional hematoxylin-and-eosin staining or by extended histopathological assessment, independently of regional lymph node status. SLN procedures were determined to be true negatives if SLNs and regional lymph nodes revealed no metastases after conventional and advanced histopathology. SLN procedures yielding tumor-negative SLNs in combination with tumor-positive regional lymph nodes were classified as false negatives. Sensitivity, negative predictive value and detection rate were calculated.

          Results

          This systematic review and meta-analysis included 8 studies describing 227 SLN procedures. A pooled sensitivity of 0.63 (95% CI 0.51–0.74), negative predictive value 0.81 (95% CI 0.73–0.86) and detection rate of 0.94 (95% CI 0.85–0.97) were found. Upstaging as a result of extended histopathological assessment was 0.15 (95% CI 0.07–0.25). In our single-center study, we included 30 patients. Five false-negative SLNs were identified, resulting in a sensitivity of 44% and negative predictive value of 80%, with a detection rate of 89.7%. Eight patients had lymph node metastases, in three cases detected after extended pathological assessment, resulting in an upstaging of 13% (3 of 23 patients with negative nodes by conventional hematoxylin and eosin staining).

          Conclusions

          Several anatomical and technical difficulties make SLNM with NIR fluorescence imaging in colon cancer particularly challenging when compared to other types of cancer. As a consequence, reports of SLNM accuracy vary widely. Future studies should try to standardize the SLNM procedure and focus on early-stage colon tumors, validation of tracer composition, injection mode and improvement of real-time optical guidance.

          Electronic supplementary material

          The online version of this article (10.1007/s10151-019-02107-6) contains supplementary material, which is available to authorized users.

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          Most cited references41

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          Sentinel Node Mapping Guided by Indocyanine Green Fluorescence Imaging: A New Method for Sentinel Node Navigation Surgery in Gastrointestinal Cancer

          Background: Recently, gastrointestinal cancer has also been identified as a target for sentinel node navigation surgery (SNNS). This study is the first to determine the feasibility of sentinel node (SN) mapping guided by indocyanine green (ICG) fluorescence imaging in gastrointestinal cancer. Methods: Our series consisted of 22 patients with gastric cancer and 26 patients with colorectal cancer who had undergone standard surgical resection. ICG solution was injected intraoperatively into the subserosa around the tumor. Fluorescence imaging was obtained by a charge-coupled device (CCD) camera with a light-emitting diode with a wavelength of 760 nm as the light source and a cut filter to filter out light with wavelengths below 820 nm as the detector. Results: Immediately after the ICG injection, lymphatic vessels draining the tumor and round-shaped SNs were visualized by their bright fluorescence. Even SNs that were not green in color could be easily and clearly visualized by ICG fluorescence imaging. The SN detection rate and mean number of SNs were 90.9% and 3.6 ± 4.5 (mean ± SD), respectively, in patients with gastric cancer, and 88.5% and 2.6 ± 2.4, respectively, in patients with colorectal cancer. Among the patients with gastric cancer, the accuracy and false-negative rates were 88.9 and 33.3%, respectively, in patients with T 1 stage cancer, and 70.0 and 60.0%, respectively, overall, in all the patients. Among the patients with colorectal cancer, the corresponding values were 100 and 0%, respectively, in patients with T 1 stage cancer, and 82.6 and 66.7%, respectively, overall, in all the patients. Conclusions: Our preliminary results show that ICG fluorescence imaging allows easy, highly sensitive and real-time imaging-guided SN mapping in patients with gastric or colorectal cancer. SN mapping guided by ICG fluorescence imaging could be a promising tool deserving further clinical exploration.
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            Micrometastases and survival in stage II colorectal cancer.

            Standard treatment of colorectal cancer includes adjuvant chemotherapy for patients with stage III disease (defined by the presence of lymph-node metastases), but not for patients with stage II tumors (who have no lymph-node metastases). However, 20 percent of patients with stage II tumors die of recurrent disease. We investigated whether the detection of micrometastases can be used to identify patients with stage II disease who are at high risk for recurrence. We analyzed 192 lymph nodes from 26 consecutive patients with stage II colorectal cancer, using a carcinoembryonic antigen-specific nested reverse-transcriptase polymerase chain reaction. Five-year follow-up information was obtained on all patients. Observed and adjusted survival rates were assessed in the patients with and the patients without micrometastases. Micrometastases were detected in one or more lymph nodes from 14 of 26 patients (54 percent). The adjusted five-year survival rate (for which only cancer-related deaths were considered) was 50 percent in this group, whereas in the 12 patients without micrometastases, the survival rate was 91 percent (P=0.02 by the log-rank test). The observed five-year survival rates were 36 percent and 75 percent, respectively (P=0.03). The groups were similar with respect to age, sex, tumor side (location in relation to the flexura lienalis), degree of tumor differentiation (grade), and diameter of the primary tumor. Molecular detection of micrometastases is a prognostic tool in stage II colorectal cancer.
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              Near-infrared (NIR) laparoscopy for intraoperative lymphatic road-mapping and sentinel node identification during definitive surgical resection of early-stage colorectal neoplasia.

              Appropriate lymphatic assessment is a cornerstone of definitive surgical resection for colorectal cancer. Near-infrared (NIR) laparoscopy may allow real-time intraoperative identification of territorial lymphatic drainage and sentinel nodes in patients with early-stage disease prior to radical basin resection.
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                Author and article information

                Contributors
                +31 20 4445234 , m.ankersmit1@vumc.nl
                Journal
                Tech Coloproctol
                Tech Coloproctol
                Techniques in Coloproctology
                Springer International Publishing (Cham )
                1123-6337
                1128-045X
                18 November 2019
                18 November 2019
                2019
                : 23
                : 12
                : 1113-1126
                Affiliations
                [1 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of Surgery, Cancer Center Amsterdam, , Amsterdam UMC-Vrije Universiteit Amsterdam, ; De Boelelaan 1117, Amsterdam, The Netherlands
                [2 ]GRID grid.10417.33, ISNI 0000 0004 0444 9382, Department of Operating Rooms and MITeC Technology Center, , Radboud University Medical Center, ; Nijmegen, The Netherlands
                [3 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Medical Library, , Amsterdam UMC, Vrije Universiteit Amsterdam, ; Amsterdam, The Netherlands
                [4 ]GRID grid.414725.1, ISNI 0000 0004 0368 8146, Department of Surgery, , Meander Medisch Centrum, ; Amersfoort, The Netherlands
                Author information
                http://orcid.org/0000-0002-4256-3720
                Article
                2107
                10.1007/s10151-019-02107-6
                6890578
                31741099
                478fe166-28fd-4d5f-b26b-8fc09ebd3d55
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 17 February 2019
                : 26 October 2019
                Categories
                Original Article
                Custom metadata
                © Springer Nature Switzerland AG 2019

                Gastroenterology & Hepatology
                sentinel lymph node,indocyanine green,irdye800cw,colon cancer
                Gastroenterology & Hepatology
                sentinel lymph node, indocyanine green, irdye800cw, colon cancer

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