Sentinel lymphadenectomy in cervical cancer using near infrared fluorescence from indocyanine green combined with technetium‐99m‐nanocolloid

Soergel, Philipp; Kirschke, Johanna; Klapdor, Rüdiger; Derlin, Thorsten; Hillemanns, Peter; Hertel, Hermann

doi:10.1002/lsm.22999

Cited by 17 publications

(13 citation statements)

References 29 publications

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“…Tc with blue dye (intrapatient comparison), with tumor-positive non-SLNs in final pathology. 31 False-negative mapping (using the alternate definition) occurred in one case (out of 33 patients). 31 In this case 99m Tc with blue dye resulted in unilateral SLN detection and consequently missed a tumor-positive SLN on the contralateral side, which was identified by ICG.…”

Section: Safety Of the Modalitiesmentioning

confidence: 99%

“…31 False-negative mapping (using the alternate definition) occurred in one case (out of 33 patients). 31 In this case 99m Tc with blue dye resulted in unilateral SLN detection and consequently missed a tumor-positive SLN on the contralateral side, which was identified by ICG. In none of the cases, any ICG negative but 99m Tc or blue dye positive SLN showed tumor infiltration.…”

Section: Safety Of the Modalitiesmentioning

confidence: 99%

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Indocyanine green versus technetium‐99m with blue dye for sentinel lymph node detection in early‐stage cervical cancer: A systematic review and meta‐analysis

et al. 2021

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Background: The fluorescent dye indocyanine green (ICG) has emerged as a promising tracer for intraoperative detection of sentinel lymph nodes (SLNs) in early-stage cervical cancer. Although researchers suggest the SLN detection of ICG is equal to the more conventional combined approach of a radiotracer and blue dye, no consensus has been reached. Aims:We aimed to assess the differences in overall and bilateral SLN detection rates with ICG versus the combined approach, the radiotracer technetium-99m ( 99m Tc) with blue dye. Methods and Results:We searched MEDLINE, Embase, and the Cochrane Library from inception to January 1, 2020 and included studies reporting on a comparison of SLN detection with ICG versus 99m Tc with blue dye in early-stage cervical cancer.The overall and bilateral detection rates were pooled with random-effects metaanalyses.From 118 studies retrieved seven studies (one cross-sectional; six retrospective cohorts) were included, encompassing 589 patients. No significant differences were found in the pooled overall SLN detection rate of ICG versus 99m Tc with blue dye. Meta-analyses of all studies showed ICG to result in a higher bilateral SLN detection rate than 99m Tc with blue dye; 90.3% (95%CI, 79.8-100.0%) with ICG versus 73.5% (95%CI, 66.4-80.6%) with 99mTc with blue dye. This resulted in a significant and clinically relevant risk difference of 16.6% (95%CI, 5.3-28.0%). With sensitivity analysis, the risk difference of the bilateral detection rate maintained in favor of ICG but was no longer significant (13.2%, 95%CI −0.8-27.3%).Conclusion: ICG appears to provide higher bilateral SLN detection rates compared to 99m Tc with blue dye in patients with early-stage cervical cancer. However, in adherence with the Grading of Recommendations, Assessment, Development, and

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Section: Safety Of the Modalitiesmentioning

confidence: 99%

Section: Safety Of the Modalitiesmentioning

confidence: 99%

Indocyanine green versus technetium‐99m with blue dye for sentinel lymph node detection in early‐stage cervical cancer: A systematic review and meta‐analysis

et al. 2021

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“…Intraoperatively, the hybrid-tracer group allowed visualization of the exact same lesions as identified on preoperative SPECT, whereas the literature indicates there could be discrepancy between SNs detected with 99m Tc-nanocolloid and those detected with free ICG (13). In total, 114 SNs were resected (Table 3; Fig.…”

Section: Intraoperative Findingsmentioning

confidence: 99%

“…In an attempt to combine the strengths of radioguidance and fluorescence guidance and to overcome the limitation of light attenuation, in prostate cancer patients ''free'' ICG has been used in combination with radioguidance (preoperative imaging, such as SPECT/CT, and intraoperative g-tracing) provided by traditional nanocolloids (e.g., 99m Tc-nanocolloid) (11). A limiting factor in the use of such a cocktail of tracers is that the individual tracers have different pharmacokinetic properties (12), which can yield a mismatch in radioactive and fluorescence findings (13). To prevent such a mismatch and to provide fully integrated radioguidance and fluorescence guidance toward the identical lesions, bimodal, or rather hybrid, tracers such as ICG-99m Tc-nanocolloid have been introduced (2,14,15).…”

mentioning

confidence: 99%

Can Intraoperative Fluorescence Imaging Identify All Lesions While the Road Map Created by Preoperative Nuclear Imaging Is Masked?

et al. 2019

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Tracers can help visualize the lymphatic drainage patterns and sentinel nodes (SNs) of individual prostate cancer patients. To determine the role of nuclear medicine in surgical guidance, in particular the positional guidance of a SPECT/CT-based 3dimensional imaging road map, in this process we studied to what extent fluorescence guidance underestimated the number of target lesions relative to radioguidance. Methods: SPECT/CT imaging was performed after intraprostatic tracer administration of either indocyanine green (ICG)-99m Tc-nanocolloid (hybrid-tracer group) or 99m Tc-nanocolloid to create a road map that depicted all SNs. Patients who received 99m Tc-nanocolloid were injected with "free" ICG immediately before surgery. Before unmasking, fluorescence guidance was used for intraoperative SN identification. This was followed by extended pelvic lymph node dissection (ePLND). After unmasking of the SPECT/CT images, the number of missed SNs was recorded and their resection was pursued when there was no risk of intraoperative complications. Results: Preoperative SPECT/ CT revealed no differences in the SN identification rate between ICG-99m Tc-nanocolloid and 99m Tc-nanocolloid. However, fluorescence guidance allowed intraoperative removal of all SNs in only 40% of patients in the hybrid-tracer group and 20% of patients in the free-ICG group. Overall, 75.9% of the intraoperatively resected SNs in the hybrid-tracer group and 51.8% of the SNs in the free-ICG group were removed solely under fluorescence guidance. During ePLND, 22 additional SNs were resected (7 in the hybrid-tracer group and 15 in the free-ICG group). After unmasking, 18 remaining SNs were identified (6 in the hybrid group and 12 in the free-ICG group). In the free-ICG group, ex vivo evaluation of the excised specimens revealed that 14 SNs removed under ePLND or after unmasking contained radioactivity but no fluorescence. Conclusion: The preoperative imaging road map provided by SPECT/CT enhanced the detection of prostate SNs in more ectopic locations in 17 of the 25 patients, and the hybrid tracer ICG-99m Tc-nanocolloid was shown to outperform free ICG. Overall, fluorescenceguided pelvic nodal surgery underestimated the number of SNs in 60%-80% of patients.

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“…6,7 Several studies have recently been initiated to reduce radicality of treatment where only sentinel lymph nodes and no parametria are removed, [8][9][10] leaving afferent lymphatic vessels accompanied with minute lymph nodes in situ. Tracers such as patent blue or infrared fluorescence from indocyanine green 11,12 allow identification of small lymphatic vessels, whereas radioactive labeling is only suitable for lymph node identification alone.…”

Section: Introductionmentioning

confidence: 99%

Evidence for disseminated tumor cells in lymphatic vessels afferent to sentinel lymph nodes in patients diagnosed with cervical cancer

et al. 2021

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Background: In patients diagnosed with cervical cancer, the purpose of lymphadenectomy is the removal of lymph nodes for diagnosis and potential treatment of metastasized tumor cells. It is unclear if afferent lymphatic vessels harbor tumor cells and, thus, may pose additional risk for recurrence or progression if not removed.Aim: In this feasibility study, we analyzed the lymphatic vessels afferent to sentinel lymph node (SLN) using a highly sensitive and specific molecular marker for cervical cancer cells.Methods and Results: Twenty patients diagnosed with cervical cancer of FIGO stage IA1 to IIB2 underwent laparoscopic SLN removal. Labeling was done using patent blue and the afferent lymphatic vessels were harvested from the parametric tissue and frozen at −80 C. HPV DNA type was evaluated in the primary tumor. Lymphatic vessels afferent to the sentinel lymph nodes were analyzed for the presence of viral oncogene transcripts of the respective HPV type. In one of 18 patients, all with tumor stage ≤IBI and pN0 by conventional histopathology, HPV mRNA could be detected in two of four lymphatic vessels, whereas at least one of the lymphatic vessel biopsies of both patients with tumors >4 cm and pN1 status was HPV mRNA positive. No clinical correlation with recurrence after a median follow-up of 9 years was noticed. Conclusion:HPV mRNA indicative of disseminated tumor cells could be detected in lymphatic vessels. The relevance of harvesting lymphatic vessels afferent to SLN in order to increase oncologic safety will have to be investigated in a future prospective study.

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Sentinel lymphadenectomy in cervical cancer using near infrared fluorescence from indocyanine green combined with technetium‐99m‐nanocolloid

Cited by 17 publications

References 29 publications

Indocyanine green versus technetium‐99m with blue dye for sentinel lymph node detection in early‐stage cervical cancer: A systematic review and meta‐analysis

Indocyanine green versus technetium‐99m with blue dye for sentinel lymph node detection in early‐stage cervical cancer: A systematic review and meta‐analysis

Can Intraoperative Fluorescence Imaging Identify All Lesions While the Road Map Created by Preoperative Nuclear Imaging Is Masked?

Evidence for disseminated tumor cells in lymphatic vessels afferent to sentinel lymph nodes in patients diagnosed with cervical cancer

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