Intraoperative Sentinel Node Identification Research Articles

Results of Using Intraoperative Sentinel Lymph Node Identification in the Surgical Management of Stage IA-IIA Non-Small Cell Lung Cancer

Results of Using Intraoperative Sentinel Lymph Node Identification in the Surgical Management of Stage IA-IIA Non-Small Cell Lung Cancer

A new bimodal approach for sentinel lymph node imaging in prostate cancer using a magnetic and fluorescent hybrid tracer.

To obtain initial data on sentinel lymph node (SLN) visualisation by pre-operative magnetic resonance imaging (MRI) and intra-operative bimodal SLN identification using a new magnetic fluorescent hybrid tracer in prostate cancer (PCa) patients. Ten patients at > 5% risk for lymph node (LN) invasion were included. The day before surgery, a magnetic fluorescent hybrid tracer consisting of superparamagnetic iron oxide nanoparticles (SPION) and indocyanine green was transrectally injected into the prostate. Five hours after injection, transversal pelvic MRI scans were recorded and T2*-weighed images were screened for pelvic LNs with SPION uptake. Intra-operatively, magnetically active and/or fluorescent SLNs were detected by a handheld magnetometer and near-infrared fluorescence imaging (FI). Extended pelvic lymph node dissection (PLND) and radical prostatectomy completed the surgery. All resected specimens were checked ex situ for magnetic activity and fluorescence and were histopathologically examined. Pre-operative MRI identified 145 pelvic LNs with SPION uptake. In total, 75 (median 6, range 3‒13) magnetically active SLNs were resected, including 14 SLNs not seen on MRI. FI identified 89 fluorescent LNs (median 8.5, range 4‒13) of which 15 LNs were not magnetically active. Concordance of the different techniques was 70% for pre-operative MRI vs. magnetometer-guided PLND and 88% for magnetic vs. fluorescent SLN detection. These are the first promising results of bimodal, magnetic fluorescent SLN detection in PCa patients. Our magnetic fluorescent hybrid approach provides the surgeon a pre-operative lymphatic roadmap by using MRI and intra-operative visual guidance through the application of a fluorescent lymphatic agent. The diagnostic accuracy of our new hybrid approach has to be evaluated in further studies. DRKS00032808. Registered 04 October 2023, retrospectively registered.

Fluorescent Guided Sentinel Lymph Mapping of the Oral Cavity with Fluorescent-Labeled Tilmanocept.

With the shift toward utilization of sentinel lymph node biopsy (SLNB) in oral cavity cancer, improved techniques for intraoperative sentinel node identification are needed. This study investigates the feasibility of fluorescently labeled tilmanoscept in SLNB in an oral cancer rabbit model. An animal study was designed using 21 healthy male New Zealand rabbits. Gallium-68-labeled tilmanocept labeled with IRDye800CW was injected submucosally into the buccal mucosa (n = 6) or lateral tongue (n = 7) followed by PET imaging. One hour after injection, SLNB was performed using fluorescence imaging followed by a bilateral neck dissection and sampling of non-nodal surrounding tissue. All tissues were measured for radioactivity and fluorescence. In addition, eight rabbits were injected with delayed SLNB performed 48 h after injection. Buccal injections all had ipsilateral SLN drainage and tongue injections exhibited 18.2% contralateral drainage. An average of 1.9 ± 1.0 SLN (range 1-5) were identified. In addition, an average of 16.9 ± 3.3 non-sentinel lymph nodes were removed per animal. SLNs had an average of 0.69 ± 0.60 percent-of-injected dose (%ID) compared with non-sentinel nodes with 0.012 ± 0.025 %ID and surrounding tissue with 0.0067 ± 0.015 %ID. There was 98.0% agreement between sentinel lymph nodes identified using fluorescence compared to radioactivity with Cohen's kappa coefficient of 0.879. In 48-h delayed SLNB, results were consistent with 97.8% agreement with radioactivity and Cohen's Kappa coefficient of 0.884. Fluorescence identified additional lymph nodes that were not identified by radioactivity, and with one false negative. Fluorescent-labeled Tc-99 m-tilmanocept represents a highly accurate adjunct to enhance SLNB for oral cavity cancer. N/A Laryngoscope, 134:1299-1307, 2024.

Contrast-enhanced ultrasound-guided sentinel lymph node biopsy in early-stage breast cancer: a prospective cohort study

ObjectiveThis study evaluated the identification efficiency of contrast-enhanced ultrasound (CEUS) for sentinel lymph nodes (SLN) to accurately represent the axillary node status in early-stage breast cancer.MethodIn total, 109 consecutive consenting patients with clinically node-negative and T1-2 breast cancer were included in this study. All patients received CEUS to identify SLN before surgery, and a guidewire was deployed to locate SLN in those who were successfully explored by CEUS. The patients underwent sentinel lymph node biopsy (SLNB), and the blue dye was used to trace SLN during the surgery. The decision to perform axillary lymph node dissection (ALND) depended on the intraoperative pathological identification of SLN by CEUS (CE-SLN). The concordance rate of pathological status between CE-SLN and dyed SLN was calculated.ResultThe CEUS detection rate was 96.3%; CE-SLN failed in 4 patients. Among the remaining 105 successful identifications, 18 were CE-SLN positive by intraoperative frozen section, and one with CE-SLN micrometastasis was diagnosed by paraffin section. No additional lymph node metastases were found in CE-SLN-negative patients. The concordance rate of pathological status between CE-SLN and dyed SLN was 100%.ConclusionCEUS can accurately represent the status of axillary lymph nodes in patients with clinically node-negative and small tumor burden breast cancer.Graphical

Indocyanine green-guided sentinel lymph node mapping during laparoscopic surgery with vaginal cuff closure but no uterine manipulator for cervical cancer.

Lymph node metastasis is a critical prognostic factor in cervical cancer. Considering the potential complications of lymphadenectomy and desirability of avoiding systemic lymphadenectomy, accurate intraoperative prediction of the existence of lymph node metastasis is important in patients undergoing surgery for cervical cancer. We evaluated the feasibility and value of indocyanine green (ICG) use for sentinel lymph node (SLN) mapping during laparoscopic surgery performed for cervical cancer. This single-center cohort study included 77 patients undergoing a new laparoscopic radical surgery method with pelvic lymphadenectomy for early-stage cervical cancer. The surgery, performed without using a uterine manipulator, included creation of a vaginal cuff. Bilateral ICG-guided SLN mapping and rapid histopathological examination were performed, and results were analyzed in relation to final histopathologic diagnoses. The SLN pelvic side-specific detection rate was 93.5%, sensitivity (SLN-positive cases/SLN-detected pelvic lymph node-positive cases) was 100%, intraoperative negative predictive value (NPV) was 97.8%, and final pathological NPV was 100%. The detection rate was significantly lower for tumors ≥ 2cm in diameter than for tumors < 2cm in diameter. Micrometastases were missed by intraoperative examination in 3 cases. The high NPV suggests the feasibility and usefulness of ICG-based SLN mapping plus rapid intraoperative examination for identification of metastatic SLNs. Use of ICG-based mapping for intraoperative identification of SLNs in patients undergoing this new laparoscopic surgery method for early-stage cervical cancer was particularly effective for tumors < 2cm in diameter. However, incorporating a search for micrometastases into rapid intraoperative histopathologic examination may be necessary.

Methods of Sentinel Lymph Node Identification in Auricular Melanoma.

Background:Sentinel lymph node biopsy is used to evaluate for micrometastasis in auricular melanoma. However, lymphatic drainage patterns of the ear are not well defined and predicting the location of sentinel nodes can be difficult. The goal of this study was to define the lymphatic drainage patterns of the ear and to compare multiple modalities of sentinel node identification.Methods:A retrospective review of a prospectively maintained database evaluated 80 patients with auricular melanoma who underwent sentinel lymph node biopsy by comparing preoperative imaging with intraoperative identification of sentinel nodes. Patients were placed into two cohorts, based on the modality of preoperative imaging: (1) planar lymphoscintigraphy only (n = 63) and (2) single-photon emission computerized tomography combined with computerized tomography (SPECT-CT) only (n = 17). Sites of preoperative mapping and sites of intraoperative identification were recorded as parotid/preauricular, mastoid/postauricular, and/or cervical.Results:In patients that underwent planar lymphoscintigraphy preoperatively (n = 63), significantly more sentinel nodes were identified intraoperatively than were mapped preoperatively in both the parotid/preauricular (P = 0.0017) and mastoid/postauricular (P = 0.0047) regions. Thirty-two nodes were identified intraoperatively that were not mapped preoperatively in the planar lymphoscintigraphy group (n = 63), two of which were positive for micrometastatic disease. In contrast, there were no discrepancies between preoperative mapping and intraoperative identification of sentinel nodes in the SPECT-CT group (n = 17).Conclusions:SPECT-CT is more accurate than planar lymphoscintigraphy for the preoperative identification of draining sentinel lymph nodes in auricular melanoma. If SPECT-CT is not available, planar lymphoscintigraphy can also be used safely, but careful intraoperative evaluation, even in basins not mapped by lymphoscintigraphy, must be performed to avoid missed sentinel nodes.

Superparamagnetic Iron Oxide Sentinel Node Tracer Injection: Effects on Breast MRI Quality.

To evaluate the MRI artifact rendered by the typical injection of a ferromagnetic tracer now being intermittently used for intraoperative sentinel node (SN) identification at our institution, and to explore its impact on postoperative imaging and management. This study was Institutional Review Board-approved and granted a waiver of consent. A database search tool was used to identify MRI exams performed on patients who had previously undergone breast-conserving surgery with use of a superparamagnetic iron oxide (SPIO) SN tracer between January 1, 2015, and May 1, 2020. MRI reports, images, and relevant demographic, oncologic, and surgical history were collected. The presence or absence of SPIO residue on breast MRI, as well as its impact on image quality, were extracted from the prospective reports. A total of 21 MRI exams were identified in 16 patients who had undergone breast-conservation therapy for cancer with use of SPIO SN tracer. Mean time from particle injection to baseline postoperative MRI exam was 10.8 months. All reports (21/21) noted evidence of SPIO residue. Of these, 5/21 were assessed as non-diagnostic; the remainder were assessed as limited. Radiologists should be aware of the use of superparamagnetic tracers for SN identification and the impact on the quality of future MRI examinations. Alternative injection approaches are being developed and sequence parameters adjusted to minimize artifact.

Hybrid Indocyanine Green–99mTc-nanocolloid for Single-photon Emission Computed Tomography and Combined Radio- and Fluorescence-guided Sentinel Node Biopsy in Penile Cancer: Results of 740 Inguinal Basins Assessed at a Single Institution

BackgroundSentinel node (SN) biopsy in penile cancer (PeCa) is typically performed using 99mTc-nanocolloid and blue dye. Recent reports suggested that the hybrid (radioactive and fluorescent) tracer indocyanine green (ICG)-99mTc-nanocolloid may improve intraoperative optical SN identification. ObjectiveThe current study aimed to confirm the reliability of ICG-99mTc-nanocolloid and to assess whether blue dye is still of added value. Design, setting, and participantsA total of 400 ≥T1G2N0 PeCa patients were staged with SN biopsy at a single European centre. SNs were preoperatively identified with lymphoscintigraphy and single-photon emission computed tomography. Intraoperatively, SNs were detected via gamma tracing, blue staining, and fluorescence imaging. Outcome measurements and statistical analysisAll patients (n=400, 740 groins) received ICG-99mTc-nanocolloid. Intraoperative SN identification rates were retrospectively evaluated. In those patients who received ICG-99mTc-nanocolloid and blue dye (n=266, 492 groins), SN visualisation rates were compared using the McNemar test. Results and limitationsIn total, 740 groins were assessed. No tracer-related (allergic) reactions were reported. All preoperatively defined SNs (n=1163) were localised intraoperatively. Of all excised SNs, 98% were detectable with gamma probe and 96% were visible with fluorescence imaging. In the analysis of the patients who received ICG-99mTc-nanocolloid and blue dye, fluorescence imaging yielded a 39% higher SN detection rate than blue dye (95% confidence interval 36–43%, p<0.001). Of the SNs that were tumour positive, 100% were intraoperatively visualised by fluorescence imaging, whereas merely 84% of the positive nodes stained blue. ConclusionsThis study confirms that ICG-99mTc-nanocolloid is a reliable SN tracer for PeCa that significantly improves optical SN detection over blue dye. Patient summaryHybrid indocyanine green (ICG)-99mTc-nanocolloid is a safe and reliable sentinel node (SN) tracer, as established in this large series of 400 penile cancer patients (740 groins). It enables accurate pre- and intraoperative SN identification and significantly improves SN detection rate compared with blue dye, without staining the surgical field or the need for an additional injection.

PD19-04 VALIDATION OF HYBRID ICG-99mTc-NANOCOLLOID FOR SENTINEL NODE BIOPSY IN A LARGE COHORT OF PENILE CANCER PATIENTS

INTRODUCTION AND OBJECTIVE: Dynamic sentinel node (SN) biopsy is an invasive lymph node (LN) staging method that is typically performed using 99mTc-nanocolloid combined with blue dye to detect micro-metastatic disease for ≥T1G2 penile cancer (PC) patients with no palpable inguinal LNs (cN0). Recent reports suggested that the hybrid tracer indocyanine green (ICG)-99mTc-nanocolloid may improve intraoperative optical SN identification relative to the blue dye. However, this evidence is supported by small sample size series. The aim of the current study was to confirm these findings relying on the largest single center cohort of PC patients who underwent SN biopsy using ICG-99mTc-nanocolloid and blue dye METHODS: 404 patients with ≥T1G2N0 penile squamous cell carcinoma were scheduled for SN biopsy and treatment of the primary tumour at a single European centre. Of those, 255 received SN biopsy using ICG-99mTc-nanocolloid and blue dye. After peritumoural injection of ICG-99mTc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Shortly before surgery, blue dye was administered in all patients using the same injection sites as the hybrid tracer. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and near-infrared fluorescence imaging (ICG). Intraoperative SN identification rates of blue dye and ICG-99mTc-nanocolloid were compared using a two-sample t-test RESULTS: There were no tracer-related adverse events. Lymphoscintigraphy and SPECT/CT visualized at least one SN in all patients. All preoperatively defined SNs were intra-operatively identified using a combination of radio-, fluorescence- and blue dye guidance. A total of 841 SNs were excised (median 3 SNs per patient; range 1-9). Of these, 95% were visible with fluorescence imaging, while only 56% were stained by blue dye (p<0.001). Pathologic analyses of the 841 SNs removed, identified 58 positive nodes in 43 patients. Of those, 100% (n=58) and 69% (n=40) were fluorescent or stained blue, respectively. In 45 patients, blue dye did not identify any LN. Of these patients, 7% had positive nodes. Conversely, fluorescence imaging using the hybrid tracer enabled optical detection of at least one SN in all patients CONCLUSIONS: The use of fluorescence improved the optical detection rate of SNs of 39% relative to blue dye. Its use is safe and can replace blue dye for SN biopsy in patients with PC Source of Funding: None

Predictive risk factors for sentinel lymph node nonvisualization on planar lymphoscintigraphy using an intratumoral injection in patients with primary breast cancer.

Lymphoscintigraphy is considered a useful tool to optimize sentinel lymph node (SLN) identification. Nonvisualization of the SLN is associated with a lower SLN identification rate. The aim of this study was to identify preoperative factors associated with SLN nonvisualization on lymphoscintigraphy. A total of 2050 consecutive SLN procedures were evaluated from clinically node-negative breast cancer patients. Planar lymphoscintigraphy was performed at 3 h after an intratumoral injection of technetium-99m-nanocolloid. This technique was used for extra-axillary SLN identification. Patient, tumor, and treatment characteristics were analyzed for association with SLN nonvisualization. Factors with a P-value less than 0.1 in univariate analysis were included in a multivariate logistic regression model. The SLN visualization rate was 86.7%. In multivariate logistic regression, age of at least 70 years [odds ratio (OR): 3.24; 95% confidence interval (CI): 2.14-4.91)], BMI of at least 30 (OR: 1.93; 95% CI: 1.39-2.69), T3/T4-tumors (OR: 2.70; 95% CI: 1.37-5.32), medially/centrally located tumors (OR: 1.52; 95% CI: 1.17-1.99), previous mantle field radiation (OR: 4.04; 95% CI: 1.74-9.35), nonpalpable tumors (OR: 1.88; 95% CI: 1.36-2.60), and presence of iodine seeds (OR: 1.35; 95% CI: 1.02-1.78) were associated significantly with nonvisualization on lymphoscintigraphy. Nonvisualization was the strongest independent predictor of unsuccessful intraoperative SLN identification (P<0.001). Overall, the SLN identification rate was 97.7% because of the use of additional imaging and blue dye. This study reports new tumor and treatment-related risk factors for nonvisualization on lymphoscintigraphy by using an intratumoral injection in primary breast cancer. We recommend a periareolar subcutaneous injection to improve SLN visualization in patients with limited prognostic and therapeutic relevance of internal mammary chain SLN identification.

Time to Procedure, Nuclear Imaging and Clinicopathological Characteristics as Predictive Factors for Sentinel Lymph Node Metastasis in Cutaneous Melanoma: A Single-Center Analysis.

Sentinel lymph node (SLN) biopsy is a widely accepted staging procedure for cutaneous melanoma patients who are at risk of clinically occult nodal metastases. Numerous predictive factors for regional lymph node metastases have been identified; however, few have been found to be reproducibly significant. Also, the role of blue dye in identification was questioned in recent trials. Time to procedure was also found to be predictive of SLN positivity, but this was not confirmed in other studies. In our study, predictive factors for metastatic involvement of SLN were analyzed, together with the role of addition blue dye in imaging on detection rate and false-negative SLN rate. An impact of time interval to procedure on the rate of SLN positivity was also explored. Data analysis was done in 362 cutaneous melanoma patients who underwent lymphoscintigraphy and SLN biopsy at our institution from 2010 to 2016, with a median follow-up of 29 months (1-98 months). To delineate the relation of each variable (demographical, time to procedure, and clinical and pathological variables, as well as the presence of in-transit nodes, the number of draining basins, and SLN localization on scintigraphy) with positive SLN status, we used univariate logistic regression with odds ratios representing effect size. Metastatic involvement SLN was found in 67 (18.8%) of 356 patients. Detection rate was similar with or without further intraoperative SLN identification with blue dye (98.8% vs 98.17%, P > 0.05). Time to procedure was not associated with higher SLN positivity rate (P > 0.05). In univariate analysis, Breslow thickness (P < 0.001), primary ulceration lesion (P = 0.001), and lymphovascular invasion (P = 0.006) were strongly correlated with SLN positivity, as well as the site of primary tumor (P = 0.024), tumor-infiltrating lymphocytes (TILs) (P = 0.021), and sex (P = 0.026). In multivariate analysis, Breslow thickness and TILs were found to be significant independent predictors of SLN status (P < 0.05). Addition of blue dye did not improve SLN detection rate; time to procedure was not found to be associated with higher SLN biopsy positivity rates. Breslow thickness and TILs, as a marker of immune response to tumor, were consistently found to be significant independent predictors of SLN status.

Indocyanine green and fluorescence lymphangiography for sentinel node identification in patients with melanoma

BackgroundInfrared fluorescence imaging with indocyanine green (ICG) is a novel method for sentinel node localization. Our objective was to assess ICG and fluorescence imaging for preoperative and intraoperative utility. Methods87 eligible patients participated in this prospective study. All patients received injection of ICG dye in addition to both methylene blue and 99mTc. Each sentinel node was assessed for the presence of each dye. ResultsICG was visible prior to incision in 44% of subjects. 99mTc identified a mean of 1.89 SLN per patient. ICG identified a mean of 1.87 SLN while methylene blue (MB) dye identified a mean of 0.71 SLN. 99mTc and ICG identified the same number of sentinel nodes per patient (P = .73) while methylene blue was inferior in its ability to localize sentinel nodes (P < .001). ConclusionOur findings indicate that ICG/fluorescence imaging has limited ability to identify the nodal basin preoperatively, but is equivalent to 99mTc for intraoperative identification of sentinel nodes and superior to MB.

Use of 99mTc-Tilmanocept as a Single Agent for Sentinel Lymph Node Identification in Breast Cancer: A Retrospective Pilot Study.

99mTc-tilmanocept received recent Food and Drug Administration approval for lymphatic mapping in 2013. However, to our knowledge, no prior studies have evaluated the use of 99mTc-tilmanocept as a single agent in sentinel lymph node (SLN) biopsy in breast cancer. Methods: We executed this retrospective pilot study to assess the ability of 99mTc-tilmanocept to identify sentinel nodes as a single agent in clinically node-negative breast cancer patients. Patients received a single intradermal injection overlying the tumor of either 18.5 MBq (0.5 mCi) of 99mTc-tilmanocept on the day of surgery or 74.0 MBq (2.0 mCi) on the day before surgery by a radiologist. Immediate 3-view lymphoscintigraphy was performed. Intraoperatively, SLNs were identified with a portable γ-probe. A node was classified as hot if the count (per second) of the node was more than 3 times the background count. Descriptive statistics are reported. Results: Nineteen patients underwent SLN biopsy with single-agent 99mTc-tilmanocept. Immediate lymphoscintigraphy identified at least 1 sentinel node in 13 of 17 patients (76.5%). Intraoperatively, at least 1 (mean, 1.7 ± 0.8; range, 1-3) hot node was identified in all patients. Three patients (15.8%) had 1 disease-positive SLN. Conclusion: In this small, retrospective pilot study, 99mTc-tilmanocept performed well as a single agent for intraoperative sentinel node identification in breast cancer. A larger, randomized clinical trial is warranted to compare 99mTc-tilmanocept as a single agent with other radiopharmaceuticals for sentinel node identification in breast cancer.

Magnetic Sentinel Lymph Node Detection in Prostate Cancer after intraprostatic Injection of Superparamagnetic Iron Oxide Nanoparticles

In prostate cancer, reliable information about the lymph node status is of great importance for accurate staging and the optimal planning of treatment. Despite recent advances in imaging, the histological detection of metastases, or pelvic lymphadenectomy (PLND), continues to be the most reliable method for lymph node staging in clinically localised prostate cancer, especially as this procedure enables the detection of small or micrometastases. Radioisotope-guided sentinel PLND (sPLND) demonstrates high sensitivity in the detection of lymph node metastases as well as low morbidity in prostate cancer because of the targeted removal of a relatively small number of lymph nodes. However, radioactive labelling is associated with limitations such as strict legal regulations, the need for a nuclear medicine department and the radioactive exposure of patients and medical staff. In order to take advantage of the targeted sentinel method while avoiding the disadvantages of radioactive labelling, the identification of sentinel lymph nodes (SLNs) by means of superparamagnetic iron oxide nanoparticles (SPIONs) was studied in breast carcinoma, and its non-inferiority compared with the established procedure with 99mtechnetium nanocolloid was demonstrated. Just like the radioactive identification of SLNs, this innovative new method for magnetic labelling and the intraoperative identification of SLNs using a hand-held magnetometer were successfully transferred to prostate cancer. Initial studies demonstrated high sensitivity in the detection of lymph node-positive patients. This method offers the additional advantage of being safe and easy to perform for a single urologist. In addition, the visualisation of SPION-marked SLNs through magnetic resonance tomography enables a precise preoperative SLN identification comparable to lymphoscintigraphy in the radioactive approach. Therefore, SLNs can be identified before and during surgical procedures in prostate cancer patients without exposure to irradiation.

MTE15.02 Lymph Node Mapping in Lung Cancer

MTE15.02 Lymph Node Mapping in Lung Cancer

Meta-analysis of aberrant lymphatic drainage in recurrent breast cancer.

Sentinel node biopsy (SNB) in recurrent breast cancer offers targeted axillary staging compared with axillary lymph node dissection (ALND) or no treatment. The evidence for lymphatic mapping in recurrent breast cancer is reviewed, focusing on aberrant drainage and its implications for patient management. A meta-analysis of studies evaluating lymphatic mapping in recurrent breast cancer was performed. Outcomes included sentinel node identification, aberrant lymphatic pathways and metastatic node rates in aberrant drainage and ipsilateral axilla. Pooled odds ratios (ORs) and 95 per cent confidence intervals (c.i.) were estimated using fixed-effect analyses, or random-effects analyses in the event of statistically significant heterogeneity. Seven studies reported data on lymphatic mapping in 1053 patients with recurrent breast cancer. The intraoperative sentinel node identification rate was 59·6 (95 per cent c.i. 56·7 to 62·6) per cent, and significantly greater when the original axillary surgery was SNB compared with ALND (OR 2·97, 95 per cent c.i. 1·66 to 5·32). The rate of aberrant lymphatic drainage identification was 25·7 (23·0 to 28·3) per cent, and significantly greater when the original axillary surgery was ALND (OR 0·27, 0·19 to 0·38). The metastatic sentinel node rate was 10·4 (8·6 to 12·3) per cent, and a significantly greater metastatic nodal burden was identified in the ipsilateral axilla (OR 6·31, 1·03 to 38·79). Lymphatic mapping is feasible in recurrent breast cancer. It avoids ALND in over 50 per cent of patients who have undergone SNB, and allows the 4 per cent of patients with metastatically involved aberrant nodes to receive targeted surgical and adjuvant therapies.

Multispectral Fluorescence Imaging During Robot-assisted Laparoscopic Sentinel Node Biopsy: A First Step Towards a Fluorescence-based Anatomic Roadmap

BackgroundDuring (robot-assisted) sentinel node (SN) biopsy procedures, intraoperative fluorescence imaging can be used to enhance radioguided SN excision. For this combined pre- and intraoperative SN identification was realized using the hybrid SN tracer, indocyanine green-99mTc-nanocolloid. Combining this dedicated SN tracer with a lymphangiographic tracer such as fluorescein may further enhance the accuracy of SN biopsy. ObjectiveClinical evaluation of a multispectral fluorescence guided surgery approach using the dedicated SN tracer ICG-99mTc-nanocolloid, the lymphangiographic tracer fluorescein, and a commercially available fluorescence laparoscope. Design, setting, and participantsPilot study in ten patients with prostate cancer. Following ICG-99mTc-nanocolloid administration and preoperative lymphoscintigraphy and single-photon emission computed tomograpy imaging, the number and location of SNs were determined. Fluorescein was injected intraprostatically immediately after the patient was anesthetized. A multispectral fluorescence laparoscope was used intraoperatively to identify both fluorescent signatures. Surgical procedureMultispectral fluorescence imaging during robot-assisted radical prostatectomy with extended pelvic lymph node dissection and SN biopsy. Measurements(1) Number and location of preoperatively identified SNs. (2) Number and location of SNs intraoperatively identified via ICG-99mTc-nanocolloid imaging. (3) Rate of intraoperative lymphatic duct identification via fluorescein imaging. (4) Tumor status of excised (sentinel) lymph node(s). (5) Postoperative complications and follow-up. Results and limitationsNear-infrared fluorescence imaging of ICG-99mTc-nanocolloid visualized 85.3% of the SNs. In 8/10 patients, fluorescein imaging allowed bright and accurate identification of lymphatic ducts, although higher background staining and tracer washout were observed. The main limitation is the small patient population. ConclusionOur findings indicate that a lymphangiographic tracer can provide additional information during SN biopsy based on ICG-99mTc-nanocolloid. The study suggests that multispectral fluorescence image–guided surgery is clinically feasible. Patient summaryWe evaluated the concept of surgical fluorescence guidance using differently colored dyes that visualize complementary features. In the future this concept may provide better guidance towards diseased tissue while sparing healthy tissue, and could thus improve functional and oncologic outcomes.

Advances in sentinel node dissection in prostate cancer from a technical perspective.

The most important feature of sentinel node biopsy for prostate cancer procedure is that staging can be improved. Sentinel nodes might be found outside the extended pelvic lymph node dissection template what renders the sentinel node additive ofextended pelvic lymph node dissection. At the same time, staging within the template can be further refined. We reviewed the literature regarding the sentinel node biopsy procedure for prostate cancer. PubMed and Embase were searched for all English-languagepublications from January 1999 to September 2014 by using the keywords as "prostatecancer" and "sentinel lymph node" plus "biopsy" "dissection" and/or "procedure." The present review discusses step-by-step sentinel node biopsy for prostate cancer. Topics of discussion are: (i) preoperative sentinel node mapping (tracers and imaging); (ii) intraoperative sentinel node identification (surgical procedure and outcome); and (iii) novelties to improve sentinel node identification (pre- and intraoperative approaches). Conventional sentinel node mapping is carried out after the injection of a (99m) Tc-based tracer and subsequent preoperative imaging; for example, lymphoscintigraphy and single-photon emission computed tomography/computed tomography. This approach allowed the detection of sentinel nodes outside the extended lymph node dissection template in 3.6-36% of men with intermediate- and high-risk prostate cancer. Hereby, an overall false negative rate of sentinel nodes was reported between 0% and 24.4%. To further refine the intraoperative sampling procedure, novel imaging methods such as fluorescence imaging have been introduced. Prospective randomized comparison studies are required to confirm the added benefit of sentinel template directed nodal dissection. A proper and obtainable end-point of such a study could be the number of removed positive nodes for carrying out nodal dissection with or without sentinel template directed dissection. Similarly, the clinical impact of novel imaging technologies requires further investigation.

SPECT/CT for SLN dissection in vulvar cancer: Improved SLN detection and dissection by preoperative three-dimensional anatomical localisation

ObjectiveIn this study, we assessed the feasibility and clinical advantages of single photon emission computed tomography with CT (SPECT/CT) for sentinel lymph node (SLN) detection in vulvar cancer. MethodsThis is a unicentric prospective trial. Vulvar cancer patients underwent preoperative SLN marking (10MBq Technetium (TC)-99m-nanocolloid) and subsequent planar lymphoscintigraphy (LSG) and SPECT/CT for SLN visualization. Directly before surgery, a patent blue dye was injected. We assessed detection rates of SPECT/CT and those of planar LSG and intraoperative detection. We analyzed the sensitivity, negative predictive value and false negative rate. ResultsAt Hannover Medical School, 40 vulvar cancer patients underwent SLN dissection after preoperative LSG and SPECT/CT. The mean diameter of all tumors in final histology was 2.23 (0.1–10.5) cm with a mean tissue infiltration of 3.93 (0.25–11) mm.In preoperative imaging, SPECT/CT identified significantly more SLNs (mean 8.7 (1–35) LNs per patient) compared to LSG (mean 5.9 (0–22) LNs, p<0.01). In addition, SPECT/CT led to a high spatial resolution and anatomical localization of SLNs. Thus, SPECT/CT identified aberrant lymphatic drainage in 7/40 (17.5%) patients. There were no significant differences, but significant correlation was found between SPECT/CT and intraoperative SLN identification. Regarding inguino-femoral LNs, for all patients who underwent complete groin dissection, sensitivity was 100%, NPV was 100% and false negative rate was 0%. ConclusionSPECT/CT leads to higher SLN identification compared to LSG in vulvar cancer. Due to its higher spatial resolution and three-dimensional anatomical localisation of SLNs, SPECT/CT provides the surgeon with important additional information, facilitates intraoperative SLN detection and predicts aberrant lymphatic drainage.

Sentinel Lymph Node Mapping of Liver.

Although the sentinel lymph node (SLN) hypothesis has been applied to many tissues and organs, liver has remained unstudied. Currently, it is unclear whether hepatic SLNs even exist. If so, they could alter the management of intrahepatic cholangiocarcinoma and other hepatic malignancies by minimizing the extent of surgery while still providing precise nodal staging. This study investigated whether invisible yet tissue-penetrating near-infrared (NIR) fluorescent light can provide simultaneous identification of both the SLN and all other regional lymph nodes (RLNs) in the liver. In 25 Yorkshire pigs, this study determined whether SLNs exist in liver and compared the effectiveness of two clinically available NIR fluorophores [methylene blue and indocyanine green (ICG)], and two novel NIR fluorophores previously described by our group (ESNF14 and ZW800-3C) for SLN and RLN mapping. In this study, ESNF14 showed the highest signal-to-background ratio and the longest retention time in SLNs without leakage to second-tier lymph nodes. The findings showed that ICG had apparent leakage to second-tier nodes, and ZW800-3C had poor migration after intraparenchymal injection. However, when injected intravenously, ZW800-3C was able to highlight all RLNs in liver during a 4- to 6-h period. Simultaneous dual-channel imaging of SLN (ESNF14) and RLN (ZW800-3C) permitted unambiguous identification and image-guided resection of SLNs and RLNs in liver. The NIR imaging technology enables real-time intraoperative identification of SLNs and RLNs in the liver of swine. If these results are confirmed in patients, new strategies for the surgical management of intrahepatic malignancies should be possible.