Intraoperative Sentinel Lymph Node Detection Research Articles

Радионуклидная диагностика сторожевых лимфатических узлов при опухолях молочной железы с радиофармацевтическим лекарственным препаратом на основе меченого технецием-99m гамма-оксида алюминия

Аim: To analyze the results of radionuclide diagnostics of sentinel lymph nodes (SLN) in patients with breast cancer (BC) with the radiotracer Sentiscan, 99mTc (manufacturer “MedicorPharma-Ural”) using the multimodal SPECT/CT at the stage of visualization. Material and methods: The study was retrospective, it included 48 patients with BC with clinical stage T2-3N0M0, who underwent radionuclide diagnostics of SLN and SPECT/CT was performed at the imaging stage. The images were evaluated visually, the intensity of the radiotracer accumulation in the lymph nodes (LN) was analyzed, SUVmax was used as a quantitative parameter. Intraoperative detection of SLN with subsequent histological examination was also carried out with the calculation of the level of the radiotracer accumulation. Results: On tomoscintigrams, LNs were visualized in 43 patients out of 48, intraoperatively ‒ in 46 cases, in 2 patients, accumulation of the radiotracer in the LN projection was noted neither according to SPECT/CT, nor intraoperatively. When analyzing the intensity of the radiotracer accumulation according to SPECT/CT data, a rather large scatter of SUVmax‒35 [10‒104]. Sentinel were considered LNs with the level of the radiotracer accumulation in them of at least 10 % of the most intense node. According to SPECT/CT data, 165 lymph nodes were identified, the average number of lymph nodes detected in one patient was 2 [1‒3], the maximum number was 6 lymph nodes. In all patients, the lymph nodes were determined in the projection of the 1st level, in 25 cases ‒ in the projection of other zones of regional lymphatic outflow. The total number of lymph nodes removed during surgery was n=247, on average 3 [2‒5] lymph nodes were removed in one patient, with a maximum of 8 nodes. Conclusion: The sensitivity of radionuclide diagnostics of SLN with Sentiscan, 99mTc was 89.6 % according to SPECT/CT and 95.8 % according to the results of intraoperative detection. The use of multimodal imaging provides information on the exact anatomical localization of the lymph nodes. In the absence of scintigraphic visualization of the radiotracer redistribution in the lymphatic collector, intraoperative detection does not lose its relevance.

The Evaluation of Sentinel Lymph Node Biopsy Using Radiocolloid in First Stage Endometrial Cancer.

Detection of a sentinel lymph node (SLN) in patients with endometrial cancer (EC) reduces the rate of unnecessary systemic lymph dissection. The aim of this study was to assess the SLN detection rate, accuracy of the method using Tc-99m-SENTI-SCINT and the rate of metastatic nodal involvement in patients with preoperative first stage EC. A prospective study of SLN biopsy of 41 patients with stage I EC was conducted after cervical application of 4mCi Tc-99m-SENTI-SCINT. Planar lymphoscintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) of the pelvis were performed, followed by site-specific lymphadenectomy in intermediate-risk patients if no SLN was detected per hemipelvis and pelvic lymphadenectomy in all high-risk patients. Pre-operative detection rate of planar lymphoscintigraphy was 80.49 [95% confidence interval (CI): 68.36-92.62] and of SPECT/CT 95.12 (95% CI: 88.52-101.7). The total intraoperative SLN detection rate was 95.12 (95% CI: 88.52-101.7) per patient and 26.83 (95% CI: 19.91-33.75) bilaterally. The average number of SLNs removed was 1.6±0.8. The most common anatomical location of SLN was the right external iliac region. The SLN metastatic rate was 17%. Both sensitivity and negative predictive value regarding metastatic involvement were 100%. The SLN detection rate, sensitivity and negative predictive value using Tc-99m-SENTI-SCINT in patients with EC in our study were high. The application of ultra-staging in the histopathological analysis of SLN increases the detection of nodal metastases and improves the staging in these patients.

Detailed preoperative lymphatic mapping by lymphoscintigraphy for sentinel node identification: a pictorial essay

AbstractPre-operative lymphatic mapping for sentinel node identification is essential for accurate staging in patients with several solid cancers and for important prognostic implications. 99mTc-labelled colloid lymphoscintigraphy and intraoperative sentinel lymph node detection using a gamma probe represent a well-established nuclear medicine technique and a detailed imaging method thanks to the advent of hybrid multi-modality SPET/CT. Through the description of numerous clinical cases, different in terms of cancer type and fields of application, we aimed to bring out the strengths and advantages of pre-operative lymphoscintigraphy that make it still today incomparable to other techniques.

NIR-II Imaging and Sandwiched Plasmonic Biosensor for Ultrasensitive Intraoperative Definition of Tumor-Invaded Lymph Nodes.

Radical lymphadenectomy remains the cornerstone of preventing tumor metastasis through the lymphatic system. Current surgical resection of lymph nodes (LNs) based on fluorescence-guided surgery (FGS) suffers from low sensitivity/selectivity with only qualitative information, hampering accurate intraoperative decision-making. Herein, we develop a modularized theranostic system including NIR-II FGS and a sandwiched plasmonic chip (SPC). Intraoperative NIR-II FGS and detection of tumor-positive lymph nodes were performed on the gastric tumor to determine the feasibility of the modularized theranostic system in defining LN metastasis. Under the NIR-II imaging window, the orthotopic tumor and sentinel lymph nodes (SLNs) were successfully excised without ambient light interference in the operating room. Importantly, the SPC biosensor achieved 100% sensitivity and 100% specificity for tumor markers and realized rapid and high-throughput intraoperative SLN detection. We propose the synergetic design of combining the NIR-II FGS and suitable biosensor will substantially improve the efficiency of cancer diagnosis and therapy follow-up.

Three-dimensional visual technique based on CT lymphography data combined with methylene blue in endoscopic sentinel lymph node biopsy for breast cancer

BackgroundThe combined application of blue dye and radioisotopes is currently the primary mapping technique used for sentinel lymph node biopsy (SLNB) in breast cancer patients. However, radiocolloid techniques have not been widely adopted, especially in developing countries, given the strict restrictions on radioactive materials. Consequently, we carried out a retrospective study to evaluate the feasibility and accuracy of three-dimensional visualization technique (3DVT) based on computed tomography-lymphography (CT-LG) in endoscopic sentinel lymph node biopsy (ESLNB) for breast cancer.MethodsFrom September 2018 to June 2020, 389 patients who underwent surgical treatment of breast cancer in our department were included in this study. The CT-LG data of these patients were reconstructed into digital 3D models and imported into Smart Vision Works V1.0 to locate the sentinel lymph node (SLN) and for visual simulation surgery. ESLNB and endoscopic axillary lymph node dissection were carried out based on this new technique; the accuracy and clinical value of 3DVT in ESLNB were analyzed.ResultsThe reconstructed 3D models clearly displayed all the structures of breast and axilla, which favors the intraoperative detection of SLNs. The identification rate of biopsied SLNs was 100% (389/389). The accuracy, sensitivity, and false-negative rate were 93.83% (365/389), 93.43% (128/137), and 6.57% (9/137), respectively. Upper limb lymphedema occurred in one patient 3 months after surgery during the 12-month follow-up period.ConclusionsOur 3DVT based on CT-LG data combined with methylene blue in ESLNB ensures a high identification rate of SLNs with low false-negative rates. It, therefore, has the potential to serve as a new method for SLN biopsy in breast cancer cases.

Preoperative detection of sentinel lymph node in patients with endometrial cancer - comparison of planar lymphoscintigraphy, spect and SPECT/CT.

Sentinel lymph node (SLN) mapping allows minimal invasive assessment of lymph node status in patients with early-stage endometrial cancer (EC). Intraoperative detection of SLNs is based on the results obtained from preoperative nuclear medical images. The purpose of this study was to compare the data obtained from planar lymphoscintigraphy (PL), single-photon emission computed tomography (SPECT), and SPECT with computed tomography (SPECT/CT) for preoperative SLN detection in patients with EC. A total of 44 images in 22 patients with early-stage EC (22 PL, 9 SPECT and 13 SPECT/CT) were analyzed. The scans were performed in the period 2018-2020 at the Institute of Pathophysiology and Nuclear Medicine in Skopje. Thirteen patients underwent PL and SPECT/CT and nine patients underwent PL and SPECT after cervical injection of 4 mCi 99mTc-SENTI-SCINT on the day of surgery. Descriptive statistics, Wilcoxon Matched Pairs Test, and Spearman rank R coefficient were used for data analyses. Twenty-two patients with mean age of 61.1 ± 7.5 and body mass index (BMI) 34.62 ± 6.4 kg/m2 were included in the study. In four patients (18.2%) SLN was not detected on PL. Detection rate on SPECT and SPECT/CT was 100%. The average number of detected SLN was 1.4 ± 1.05, 2.2 ± 1.1 и 2.15 ± 1.1 on PL, SPECT and SPECT/CT respectively. We found a statistically significant difference in the number of detected SLNs on PL vs SPECT/CT (p = 0.0077). The most common SLN location on SPECT/CT was the right internal iliac followed by the left common iliac region. The results of the presented study indicate a higher diagnostic value of SPECT/CT in terms of SLN detection and exact anatomic localization as compared to planar lymphoscintigraphy (PL).

Toluidine blue for the detection of sentinel lymph nodes in patients with thyroid cancer

Thyroid cancer (TC) demonstrates steady growth in incidence worldwide and remains an urgent problem in oncology. The detection of sentinel lymph nodes (SLN) with a selective dye and further histological examination in selecting the proper (personalized) surgical strategy and the volume of surgical intervention for clinically undetermined regional lymph nodes. The purpose of the study is to evaluate the effectiveness and safety of intraoperative detection of SLN with a 1% toluidine blue aqueous solution. The significant tasks are to identify the pattern of TC metastases to cervical lymph nodes, to establish the prevalence of "skip" metastases, to compare the frequency of complications after total thyroidectomy and central neck dissection and lateral neck dissection with total thyroidectomy and central neck dissection, and to determine the feasibility of the application of lateral neck dissections in patients with papillary and follicular TC without metastases to regional lymph nodes (according to physical examination and ultrasound). According to our data the SLN identification rate was 97.6%. Sensitivity, specificity, positive predictive value, negative predictive value, and frequency of false negative and false positive results was 89.2, 94.6, 88.03, 95.16, 10.8, and 5.4%, respectively. The most common metastasis was in the central neck compartment (83.7%). Skip metastases were determined in 4.9% of patients. The low prevalence of "skip" metastases and a significant risk of postoperative complications (wound exudation, lymphorrhagia, inflammation, hypoparathyroidism, paresis of the vocal cords) support the idea that lateral neck dissection is appropriate only in cases of confirmed metastases by physical examination and/or ultrasound at the preoperative stage.

Sentinel lymph node biopsy in breast cancer after neoadjuvant therapy using a magnetic tracer versus standard technique: A multicentre comparative non-inferiority study (IMAGINE-II)

IntroductionPrevious studies have shown that a magnetic tracer technique using superparamagnetic iron oxide (SPIO) and a manual magnetometer (Sentimag, SM) is as effective as the standard technique using a radioisotope injection and a gamma probe (GP) for the detection of sentinel lymph nodes (SLNs) in breast cancer (BC) patients. This study was designed to investigate the performance of SM for post-neoadjuvant (NAT) SLN biopsy in BC patients. Materials and methodsPost-NAT BC patients were recruited from five centres. Readings of SLNs were recorded in transcutaneous, intraoperative and ex vivo scenarios by both GP and SM techniques. SLNs were assessed by OSNA (One-Step Nucleic Acid Amplification). ResultsA total of 89 patients were included. At the patient level, the transcutaneous and intraoperative SLN detection rate was 97.8% by both techniques. At the node level, the GP detection rate intraoperatively was lower than that of SM (93.8% vs. 99.2%), with a concordance rate of 93% (90% CI 1.25; 9.44). The ex vivo detection rate was lower for GP compared to SM both per patient 96.6% vs. 97.8%, and per node 90.6% vs. 98.4% (90% CI -2.03; 4.22 and 1.82; 13.68, respectively). Furthermore, the detection rate of pathologically positive SLNs per patient and per node was lower for GP than SM both intraoperatively and ex vivo. These results showed the non-inferiority of SM intraoperatively per node (90% CI -4.89; 20.89) and ex vivo per patient (90% CI -2.38; 29.66). ConclusionOur study showed the non-inferiority of SM compared to GP for detecting SLNs in post-NAT BC patients.

Preoperative planar lymphoscintigraphy allows for sentinel lymph node detection in 51 dogs improving staging accuracy: Feasibility and pitfalls.

Sentinel lymph node (SLN) mapping is the current gold standard for the oncological staging of solid malignancies in humans. This prospective observational study describes the feasibility and the limits of preoperative lymphoscintigraphy for SLN detection in dogs with spontaneous malignancies and the improvements in staging accuracy. Client‐owned dogs with confirmed malignant neoplasia and absence of distant metastasis were prospectively enrolled. Lymphoscintigraphy was performed after the peritumoral injection of Technetium‐99m labeled nanocolloids. Regional dynamic and static images were acquired, with and without masking of the injection site with a lead shield. The dogs were then subjected to surgery for tumor excision and SLN extirpation. Intraoperative SLN detection was performed by combining methylene blue dye and a dedicated gamma probe. Overall, 51 dogs with a total of 60 solid malignant tumors were enrolled. Lymphoscintigraphy identified at least one SLN in 57 of 60 cases (95%). The SLN did not always correspond to the regional lymph node (35/57, 61.4%). The use of a lead shield, masking the injection site, markedly improved the SLN visibility. The median time of SLN appearance was 11.4 ± 9.3 min. No side effects were observed. Preoperative lymphoscintigraphy allows for SLN detection in dogs and can improve staging accuracy by either identifying the SLN in a different lymphosome than clinically expected or discriminating the draining node in uncertain cases. The combined use of preoperative and intraoperative techniques is recommended to increase the SLN detection rate.

Paraaortic sentinel lymph node detection in intermediate and high-risk endometrial cancer by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR).

ObjectiveWe aimed to evaluate the accuracy of sentinel lymph node (SLN) mapping with transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) to detect lymph node (LN) metastases, in patients with intermediate and high-risk endometrial cancer (EC), focusing on its performance to detect paraaortic involvement.MethodsProspective study including women with preoperative intermediate or high-risk EC, according to ESMO-ESGO-ESTRO consensus, who underwent SLN mapping using the TUMIR approach. SLNs were preoperatively localized by planar and single photon emission computed tomography/computed tomography images, and intraoperatively by gamma-probe. Immediately after SLN excision, all women underwent systematic pelvic and paraaortic lymphadenectomy by laparoscopy.ResultsThe study included 102 patients. The intraoperative SLN detection rate was 79.4% (81/102). Pelvic and paraaortic drainage was observed in 92.6% (75/81) and 45.7% (37/81) women, respectively, being exclusively paraaortic in 7.4% (6/81). After systematic lymphadenectomy, LN metastases were identified in 19.6% (20/102) patients, with 45.0% (9/20) showing paraaortic involvement, which was exclusive in 15.0% (3/20). The overall sensitivity and negative predictive value (NPV) of SLNs by the TUMIR approach to detect lymphatic involvement were 87.5% and 97.0%, respectively; and 83.3% and 96.9%, for paraaortic metastases. After applying the MSKCC SLN mapping algorithm, the sensitivity and NPV were 93.8% and 98.5%, respectively.ConclusionThe TUMIR method provides valuable information of endometrial drainage in patients at higher risk of paraaortic LN involvement. The TUMIR approach showed a detection rate of paraaortic SLNs greater than 45% and a high sensitivity and NPV for paraaortic metastases in women with intermediate and high-risk EC.

Novel Experience in Hybrid Tracers: Clinical Evaluation of Feasibility and Efficacy in Using ICG-99mTc Nanotop for Sentinel Node Procedure in Breast Cancer Patients.

The clinical introduction of a radioactive and fluorescent hybrid tracer allowed for preoperative lymphatic mapping and intraoperative real-time fluorescence tracing of the sentinel lymph node (SLN) by a single injection. The aim of this feasibility study is to evaluate the first-in-human use of the hybrid tracer by combining indocyanine green (ICG) and radiocolloid based on Nanotop compound (99mTc Nanotop) for SLN biopsy (SLNB) in breast cancer patients. The day before surgery, ICG-99mTc Nanotop was injected periareolarly in breast cancer patients scheduled for SLNB. Planar lymphoscintigraphic (PL) and SPECT/CT images were then acquired. An intraoperative optonuclear probe was used to detect SLN gamma and fluorescent signals. The harvested SLNs were examined by hematoxylin-eosin staining, and patients were clinically evaluated 1 month after surgery. Twenty-one consecutive patients were enrolled. The PL and SPECT/CT techniques identified at least 1 SLN in all patients for a preoperative sentinel detection rate of 100%. SPECT/CT revealed 3 additional lymph nodes in the same nodal basin, which had not been visualized on conventional PL (κ = 0.747; P < 0.005). All 30 preoperative SLNs were localized and excised up to 16 hours after injection. The counts measured via gamma tracing showed a very strong correlation with those measured via near-infrared fluorescent tracing (P < 0.005, r = 0.964). No adverse reactions were observed. The SLNB technique used with the ICG-99mTc Nanotop tracer resulted to be feasible, reliable, and safe. This hybrid compound allowed us to obtain excellent performance in terms of both preoperative lymphatic mapping and intraoperative SLN detection in breast cancer patients.

Correlation between ferromagnetic and isotopic tracers for sentinel lymph node detection in cutaneous melanoma: IMINEM study.

The usefulness of sentinel lymph node biopsy (SLNB) in staging cutaneous melanoma has been proven. Therefore, different tracers have been used to identify the sentinel lymph nodes (SLNs). The use of isotopic tracers together with radioactivity detectors allowed a much more precise and direct approach to the SLNs. However, not all centres have access to a Nuclear Medicine department hindering sentinel lymph node detection (SLND) and consequently, other markers such as ferromagnetic tracers have been evaluated looking for the same advantages and effectiveness as isotopic tracers. Ferromagnetic tracers have proven their usefulness in other cancer entities such as breast, prostate and thyroid cancer. The objective was to assess the detection and concordance rates between isotopic and ferromagnetic techniques for SLNB in cutaneous melanoma. Isotopic SLNB technique and ferromagnetic tracer were compared for cutaneous melanoma in a non-inferiority multicentre prospective study carried out in six Spanish hospitals. A total of 60 patients were recruited and 133 lymph nodes removed. The detection rate was slightly higher with ferromagnetic tracer in head-neck and trunk melanomas, and with isotopic tracer in limbs. The patients' and nodes' concordance rates between both techniques for ex vivo samples were 95% and 86% for head-neck and trunk tumours and 97% and 93% for limbs tumours, respectively. The concordance rates for involved nodes were 100% and 88.2% for patients and nodes, respectively. The intraoperative detection and biopsy of SLN in cutaneous melanoma using a ferromagnetic was a reliable alternative method to the isotopic technique in cutaneous melanomas.

Sentinel Lymph Node Biopsy in Breast Cancer with 99mTc-Tilmanocept: A Multicenter Study on Real-Life Use of a Novel Tracer

99mTc-tilmanocept is a novel radiopharmaceutical for sentinel lymph node (SLN) biopsy in breast cancer. Our aim was to describe results with 99mTc-tilmanocept in a heterogeneous group of breast cancer patients scheduled for SLN biopsy. Methods: Radiotracer preparation followed the manufacturer's indications. Local protocols for SLN detection within 9 participant centers were not changed for the entire duration of the study. In total, 344 patients with T1-T4, N0-N2 breast cancer (352 lesions) were included. Superficial (intradermal or periareolar) or deep (peritumoral or intratumoral) injections were performed. The doses were adjusted depending on the scheduled time for surgery. Results: Lymphoscintigraphy was able to depict at least 1 SLN in 339 of 352 breast lesions (96.3%), and the intraoperative SLN detection rate reached 97.2%. On univariable analysis, SLN detection rates did not differ by age, clinical T or N stage, tumor location, histologic subtype, or prior neoadjuvant therapy. Lymphoscintigraphy showed higher SLN detection in patients with a normal weight (body mass index < 25) than in those who were overweight or obese (body mass index ≥ 25), at 99.2% versus 94.6%, respectively (P = 0.031). The proportion of patients with preoperative lymphoscintigraphic detection or excised SLNs was higher with superficial than deep injections. Reinjected cases were significantly lower when superficial injection was chosen first (P < 0.001). Injection site and the tumor markers human epidermal growth factor receptor 2 and estrogen receptor had an impact on preoperative SLN visualization and intraoperative localization. In 80 cases, SLN biopsy resulted in a positive lymph node. During a mean follow-up of 19 mo, no axillary recurrences were observed. Conclusion: Whatever the protocol, 99mTc-tilmanocept showed good results in a heterogeneous breast cancer population, although the best results were achieved when a superficial injection was chosen.

Influence of 99m-Tc-Nanocolloid Activity Concentration on Sentinel Lymph Node Detection in Endometrial Cancer: A Quantitative SPECT/CT Study.

This study evaluates quantitative combined single photon emission tomography/computed x-ray tomography (SPECT/CT) to assess the influence of radiotracer concentration on detection of sentinel lymph nodes (SLN) in endometrial cancer (EC). Eighty EC patients underwent pericervical 99m-Tc-nanocolloid injection followed by SPECT/CT. The subgroup of patients with failed SLN detection in SPECT/CT (n = 20) was compared to match-paired patients showing at least two SLNs. Results of intraoperative gamma probe measurements and quantitative SPECT/CT were used for comparison. In patients with detection failure, the percentage of injected dose, absolute activity, and volume of the injection site were significantly lower (30 ± 24% vs. 55 ± 19%; p = 0.01, 43 ± 36 MBq vs. 73 ± 33 MBq; p = 0.04, and 183 ± 164 mL vs. 266 ± 164 mL; p = 0.03) while mean activity concentration in liver, spleen, and bone marrow was significantly higher (p = 0.02). Activity concentration (>33 KBq/mL) and absolute activity (>73 MBq) of injection areas correlated with successful intraoperative SLN detection. In a subgroup of 19 SLNs, a correlation between SPECT/CT-derived uptake and intraoperative count rate was found (R2 = 0.8; p < 0.001). SLN detection in EC patients depended on high radiotracer activity at the cervical injection site. Quantitative SPECT/CT could predict successful intraoperative SLN detection and may help to optimize injection technique.

Sentinel lymph node biopsy in oral–oropharyngeal squamous cell carcinoma: standards, new technical procedures, and clinical advances

To provide substantial coverage and critical appraisal of standards as well as new technical procedures and clinical advances concerning sentinel lymph node biopsy (SNB) in oral squamous cell carcinoma (OSCC). The MEDLINE database was searched via the PubMed interface up to January 2019 for the following MeSH heading: “sentinel lymph node biopsy” and “squamous cell carcinoma of head and neck”. SNB exists as an alternative to elective neck dissection (END) in OSCC. Pre-surgical planar lymphoscintigraphy with intra-operative hand-held gamma probe allows using SNB. Furthermore, the contribution of pre-surgical SPECT/CT improves the sentinel lymph node (SLN) roadmap in sites that are closer to the injection site. Portable gamma camera and freehand SPECT are not yet routine clinical practice, but can further improve intra-operative SLN detection. However, the difficulty in detecting SLNs located closer to the injection site persists. SNB with combined radioactive and near-infrared fluorescence guidance is an attractive option for improving spatial resolution of radio-guided techniques while maintaining depth penetration. Numerous studies have demonstrated that SNB can be proposed for accurate histopathological staging of the neck and the guidelines support the introduction of SNB as an alternative to END in T1/T2 N0 OSCC patients. New hybrid imaging techniques, which are offering new possibilities to assist clinicians and surgeons in localizing the site of uptake in sentinel node detection, need to be confirmed in ongoing and future clinical trials. In the future, the integration of new PET tracers could continue along the route mapped out in SNB.

Magnetic resonance sentinel lymph node imaging and magnetometer-guided intraoperative detection in prostate cancer using superparamagnetic iron oxide nanoparticles.

PurposeSentinel lymph node (LN) dissection (sLND) using a magnetometer and superpara-magnetic iron oxide nanoparticles (SPION) as a tracer was successfully applied in prostate cancer (PCa). The feasibility of sentinel LN (SLN) visualization on MRI after intraprostatic SPION injection has been reported. In the present study, results of preoperative MRI identification of SLNs and the outcome of subsequent intraoperative magnetometer-guided sLND following intraprostatic SPION injection were studied in intermediate- and high-risk PCa.Patients and methodsA total of 50 intermediate- and high-risk PCa patients (prostate-specific antigen >10 ng/mL and/or Gleason score ≥7) scheduled for radical prostatectomy with magnetometer-guided sLND and extended pelvic LND (eLND), were included. Patients underwent MRI before and one day after intraprostatic SPION injection using T1-, T2-, and T2*-weighted sequences. Diagnostic rate per patient was established. Distribution of SLNs per anatomic region was registered. Diagnostic accuracy of sLND was assessed by using eLND as a reference standard.ResultsSPION-MRI identified a total of 890 SLNs (median 17.5; IQR 12–22.5). SLNs could be successfully detected using MRI in all patients (diagnostic rate 100%). Anatomic SLN distribution: external iliac 19.2%, common iliac 16.6%, fossa obturatoria 15.8%, internal iliac 13.8%, presacral 12.1%, perirectal 12.0%, periprostatic 3.7%, perivesical 2.3%, and other regions 4.4%. LN metastases were intraoperatively found in 15 of 50 patients (30%). sLND had a 100% diagnostic rate, 85.7% sensitivity, 97.2% specificity, 92.3% positive predictive value, 94.9% negative predictive value, false negative rate 14.3%, and 2.8% additional diagnostic value (LN metastases only outside the eLND template).ConclusionMR scintigraphy after intraprostatic SPION injection provides a roadmap for intraoperative magnetometer-guided SLN detection and can be useful to characterize a reliable lymphadenectomy template. Draining LN from the prostate can be identified in an unexpectedly high number, especially outside the established eLND template. Further studies are required to analyze discordance between the number of pre- and intraoperatively identified SLNs.

Molecular Imaging of endometrial sentinel lymph nodes utilizing fluorescent-labeled Tilmanocept during robotic-assisted surgery in a porcine model.

Molecular imaging with a fluorescent version of Tilmanocept may permit an accurate and facile detection of sentinel nodes of endometrial cancer. Tilmanocept accumulates in sentinel lymph nodes (SLN) by binding to a cell surface receptor unique to macrophages and dendritic cells. Four female Yorkshire pigs underwent cervical stromal injection of IRDye800-Tilmanocept, a molecular imaging agent tagged with near-infrared fluorescent dye and radiolabeled with gallium-68 and technetium-99m. PET/CT scans 1.5 hours post-injection provided pre-operative SLN mapping. Robotic-assisted lymphadenectomy was performed two days after injection, using the FireFly imaging system to identify nodes demonstrating fluorescent signal. After removal of fluorescent nodes, pelvic and periaortic node dissections were performed. Nodes were assayed for technetium-99m activity, and SLNs were established using the “10%-rule”, requiring that the radioactivity of additional SLNs be greater than 10% of the “hottest” SLN. Thirty-four nodal samples were assayed ex vivo for radioactivity. All the SLNs satisfying the “10%-rule” were detected using the FireFly system. Five fluorescent nodes were detected, corresponding with preoperative PET/CT scan. Three pigs had one SLN and one pig had two SLNs, with 100% concordance between fluorescence and radioactivity. Fluorescent-labeled Tilmanocept permits real-time intraoperative detection of SLNs during robotic-assisted lymphadenectomy for endometrial cancer in a porcine model. When radiolabeled with gallium-68, Tilmanocept allows for preoperative localization of SLNs using PET/CT, and shows specificity to SLNs with persistent fluorescent signal, detectable using the FireFly system, for two days post-injection. In conclusion, these findings suggest that a phase I trial in human subjects is warranted, and that a long-term goal of an intra-operative administration of non-radioactive fluorescent-labeled Tilmanocept is possible.

Feasibility of intraoperative detection of sentinel lymph nodes with 89-zirconium-labelled nanocolloidal albumin PET-CT and a handheld high-energy gamma probe

BackgroundPET/CT lymphoscintigraphy using 89Zr-nanocolloidal albumin has the potential to improve the preoperative identification of sentinel lymph nodes (SLNs), especially if located in the near proximity of the primary tumour. This study aims to demonstrate the feasibility of PET/CT lymphoscintigraphy followed by intraoperative detection of 89Zr-nanocolloidal albumin containing SLNs with the use of a handheld high-energy gamma probe.MethodsPET/CT lymphoscintigraphy was performed after peritumoural injection of 89Zr-nanocolloidal albumin in five patients with oral cavity carcinoma planned for surgical resection. SLN biopsy procedure was performed 18 h later. SLNs were detected using detailed information of PET/CT and the high-energy gamma probe.ResultsIn all patients, SLNs were identified on PET/CT lymphoscintigraphy. Intraoperative detection using the high-energy gamma probe was possible in 10 of 13 SLNs, at a short distance from the SLN.ConclusionsThis study demonstrates that intraoperative detection of SLNs containing 89Zr-nanocolloidal albumin using a handheld high-energy gamma probe is feasible, but its clinical use and sensitivity seem to be limited.Trial registrationCCMO NL37222.092.11

Abstract IA13: Real-time near-infrared fluorescence tracer imaging to guide sentinel node biopsy and tumor detection in head and neck cancer

Abstract Introduction: Near-infrared fluorescence (NIRF) imaging is an emerging technology with several important applications in oncologic surgery. Using fluorescent dyes and dedicated camera systems, real-time intraoperative imaging is provided to guide surgical procedures and allow for instant decision-making. NIRF imaging has the potential to improve the Sentinel Node Biopsy (SNB) procedure for staging of oral cavity cancer by facilitating intraoperative visual identification of the sentinel lymph node (SN). Also, NIRF imaging may be used in the search of head and neck unknown primaries (CUP) in combination with transoral robotic surgery (TORS). The feasibility of NIRF imaging for intraoperative SN detection was investigated in a series of oral cavity cancer patients. In addition, our initial experience of using NIRF imaging during TORS for detection of oropharyngeal cancer will also be reported (ongoing study). Methods: (1) A prospective study of patients with primary oral squamous cell carcinoma (OSCC) planned for tumor resection and SNB. Thirty patients were injected peritumorally with a bimodal tracer (ICG-99mTc-Nanocoll) followed by lymphoscintigraphy (LSG) and SPECT/CT to define the SNs and their anatomical location preoperatively. SNs were detected intraoperatively with a hand-held gamma-probe and a hand-held NIRF camera. (2) In a minor prospective series of patients with oropharyngeal cancer undergoing TORS Indocyanin Green (ICG) was systematically injected preoperatively. The aim was to guide primary tumor detection using the firefly NIRF modality incorporated in the Da Vinci Si robotic system. Results: (1) In the SNB study, 29 of 30 subjects (97%), all preoperatively defined SNs could be identified intraoperatively using a combination of radioactive and fluorescence guidance. Eleven of 94 SNs (12%) could only be identified in vivo using NIRF imaging and the majority of those were located in level 1 close to the primary tumor. (2) In the pilot ICG TORS study, the additional use of ICG for primary tumor identification was varying. Conclusions: Intraoperative NIRF imaging as a tool to guide cancer surgery seems promising and further exploration of this novel technology is warranted. A combined fluorescent and radioactive tracer for SNB is feasible and the additional use of NIRF imaging may improve the accuracy of SN identification in oral cancer patients. Intraoperative fluorescence guidance seems of particular value, when SNs are located in close proximity to the injection site. Combined TORS and NIRF imaging showed with a varying quality the localization of the oropharyngeal cancer. The combined procedure may have a potential role in the diagnostic algorithm in head and neck CUP patients facilitating the detection of the primary tumor. Citation Format: Christian von Buchwald, Anders Christensen, Niclas Rubek, Karina Juhl, Birgitte Charabi, Jann Mortensen, Katalin Kiss, Andreas Kjær. Real-time near-infrared fluorescence tracer imaging to guide sentinel node biopsy and tumor detection in head and neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA13.

The role of sentinel lymph node mapping in small animal veterinary medicine: A comparison with current approaches in human medicine.

The relevance of regional lymph node (LN) assessment to quantify the metastatic spread of cancer is well recognized in veterinary oncology. Evaluation of LNs is critical for tumour staging. However, sampling the correct LN may not be possible without sentinel lymph node (SLN) mapping. Methods for diagnostic imaging and intraoperative detection of SLNs are well established in human medicine, in particular, the combination of lymphoscintigraphy and intraoperative application of blue dyes. Nevertheless, alternative imaging techniques are available and have gained increasing interest. Successful implementation of these techniques in dogs have been reported in both clinical and experimental studies. This review aims to provide an overview of SLN mapping techniques in human and veterinary medicine.