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Introduction: Fluorescence guidance is an upcoming methodology to improve surgical accuracy. Challenging herein is the identification of the minimum dose at which the tracer can be detected with a clinical-grade fluorescence camera. Using a hybrid tracer such as indocyanine green (ICG)-(99m)Tc-nanocolloid, it has become possible to determine the accumulation of tracer and correlate this to intraoperative fluorescence-based identification rates. In the current study, we determined the lower detection limit of tracer at which intraoperative fluorescence guidance was still feasible., Methods: Size exclusion chromatography (SEC) provided a laboratory set-up to analyze the chemical content and to simulate the migratory behavior of ICG-nanocolloid in tissue. Tracer accumulation and intraoperative fluorescence detection findings were derived from a retrospective analysis of 20 head-and-neck melanoma patients, 40 penile and 20 prostate cancer patients scheduled for sentinel node (SN) biopsy using ICG-(99m)Tc-nanocolloid. In these patients, following tracer injection, single photon emission computed tomography fused with computed tomography (SPECT/CT) was used to identify the SN(s). The percentage injected dose (% ID), the amount of ICG (in nmol), and the concentration of ICG in the SNs (in μM) was assessed for SNs detected on SPECT/CT and correlated with the intraoperative fluorescence imaging findings., Results: SEC determined that in the hybrid tracer formulation, 41 % (standard deviation: 12 %) of ICG was present in nanocolloid-bound form. In the SNs detected using fluorescence guidance a median of 0.88 % ID was present, compared to a median of 0.25 % ID in the non-fluorescent SNs (p-value < 0.001). The % ID values could be correlated to the amount ICG in a SN (range: 0.003-10.8 nmol) and the concentration of ICG in a SN (range: 0.006-64.6 μM)., Discussion: The ability to provide intraoperative fluorescence guidance is dependent on the amount and concentration of the fluorescent dye accumulated in the lesion(s) of interest. Our findings indicate that intraoperative fluorescence detection with ICG is possible above a μM concentration.

Purpose: Lymphoscintigraphic imaging and adequate interpretation of the lymphatic drainage pattern is an essential step in the sentinel lymph node biopsy (SLNB) procedure. In oral cancer, identification of the sentinel lymph node (SLN) can be challenging. In this study, interobserver variability in defining SLNs on lymphoscintigrams was evaluated in patients with T1-T2 stage N0 oral cancer., Methods: Sixteen observers (head and neck surgeons, nuclear medicine physicians or teams of both) from various institutes were asked which criteria they use to consider a hot focus on the lymphoscintigram as SLN. Lymphoscintigrams of 9 patients with 47 hot foci (3-9 per patient) were assessed, using a scale of 'yes/equivocal/no'. Bilateral drainage was seen in four of nine cases. In three cases additional late single photon emission computed tomography (SPECT)/CT scanning was performed. Interobserver variability was evaluated by kappa (к) analysis, using linear weighted pairwise comparison of the observers. Conservative (equivocal analysed as no) and sensitive (equivocal analysed as yes) assessment strategies were investigated using pairwise kappa analysis., Results: Various definitions of SLN on lymphoscintigrams were given. Interobserver variability of all cases using a 3-point scale showed fair agreement (71%, к(w) = 0.29). The conservative and sensitive analyses both showed moderate agreement: conservative approach к = 0.44 (in 80% of the hot foci the observers agreed) and sensitive approach к = 0.42 (81%) respectively. Multidisciplinary involvement in image interpretation and higher levels of observer experience appeared to increase agreement., Conclusion: Among 16 observers, there is practice variation in defining SLNs on lymphoscintigrams in oral cancer patients. Interobserver variability of lymphoscintigraphic interpretation shows moderate agreement. In order to achieve better agreement in defining SLNs on lymphoscintigrams specific guidelines are warranted.

Purpose: For oral cavity malignancies, sentinel lymph node (SLN) mapping is performed by injecting a radiocolloid around the primary tumour followed by lymphoscintigraphy. Surgically, SLNs can then be localized using a handheld gamma ray detection probe. The aim of this study was to evaluate the added value of intraoperative fluorescence imaging to the conventional radioguided procedure. For this we used indocyanine green (ICG)-(99m)Tc-nanocolloid, a hybrid tracer that is both radioactive and fluorescent., Methods: Fourteen patients with oral cavity squamous cell carcinoma were peritumourally injected with ICG-(99m)Tc-nanocolloid. SLNs were preoperatively identified with lymphoscintigraphy followed by single photon emission computed tomography (SPECT)/CT for anatomical localization. During surgery, SLNs were detected with a handheld gamma ray detection probe and a handheld near-infrared fluorescence camera. Pre-incision and post-excision imaging with a portable gamma camera was performed to confirm complete removal of all SLNs., Results: SLNs were preoperatively identified using the radioactive signature of ICG-(99m)Tc-nanocolloid. Intraoperatively, 43 SLNs could be localized and excised with combined radio- and fluorescence guidance. Additionally, in four patients, an SLN located close to the primary injection site (in three patients this SLN was located in level I) could only be intraoperatively localized using fluorescence imaging. Pathological analysis of the SLNs revealed a metastasis in one patient., Conclusion: Combined preoperative SLN identification and intraoperative radio- and fluorescence guidance during SLN biopsies for oral cavity cancer proved feasible using ICG-(99m)Tc-nanocolloid. The addition of fluorescence imaging was shown to be of particular value when SLNs were located in close proximity to the primary tumour.