Lymphoscintigraphy Imaging Research Articles

Concordance between freehand SPECT and conventional scintigraphy for sentinel lymph node detection in breast cancer

IntroductionFreehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning.The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). Materials and methods100 patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60−90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. ResultsThe observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). ConclusionFreehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.

Identifying Functional Lymph Nodes in Lower Extremity Lymphedema Patients: The Role of High-frequency Ultrasound.

Lymph nodes may play a potential role in lymphedema surgery. Radiologic evaluation of nodes may reveal the status of pathologic conditions but with limited accuracy. This study is the first to evaluate the efficacy of ultrasound in detecting functioning nodes in lymphedema patients and presents a criterion for determining the functionality of the lymph nodes. This retrospective study reviews 30 lower extremity lymphedema cases which were candidates for lymph node to vein anastomosis. Lymphoscintigraphy and magnetic resonant lymphangiography (MRL) imaging were compared with ultrasound features which were correlated to intraoperative indocyanine green (ICG) nodal uptake as an indication of functionality. Majority were International Society of Lymphology stage 2 late (50.0%) and stage 3 (26.7%). ICG positive uptake (functioning nodes) was noted in 22 (73.3%), while 8 patients (26.6%) had negative uptake (nonfunctioning). Ultrasound had significantly the highest specificity (100%) for identifying functional nodes followed by lymphoscintigraphy (55%) and MRL (36%; p = 0.002, p < 0.001, respectively). This was associated with 100% positive predictive value compared against lymphoscintigraphy (44%) and MRL (36%; p < 0.001 for both). The identified ultrasound imaging criteria for functioning lymph node were oval lymph node shape (Solbiati Index), morphology, vascularity pattern, and vascularity quantification. The use of ultrasound in nodal evaluation was proven effective in different pathologic conditions and demonstrated the best prediction for functionality of the lymph node based on the new evaluation criteria.

The Sentinel Node and Occult Lesion Localization (SNOLL) Technique Using a Single Radiopharmaceutical in Non-palpable Breast Lesions.

In order to perform a full surgical resection on non-palpable breast lesions, a current method necessitates correct intraoperative localization. Additionally, because it is an important prognostic factor for these patients, the examination of the lymph node status is crucial. The aim of this study was to evaluate the efficiency of the sentinel node and occult lesion localization (SNOLL) technique in localizing nonpalpable breast lesions together with sentinel lymph node (SLN) using a single radiotracer, that is, nanocolloid particles of human serum albumin (NC) labeled with technetium-99m (99mTc). 39 patients were included, each having a single non-palpable breast lesion and clinically no evidence of axillary disease. Patients received 99mTc- NC intratumorally on the same day as surgery under the guidance of ultrasound. Planar and single-photon emission computed tomography/computed tomography lymphoscintigraphy were performed to localize the breast lesion and the SLN. The occult breast lesion and SLN were both localized using a hand-held gamma-probe, which was also utilized to determine the optimal access pathway for surgery. In order to ensure a radical treatment in a single surgical session and reduce the amount of normal tissue that would need to be removed, the surgical field was checked with the gamma probe after the specimen was removed to confirm the lack of residual sources of considerable radioactivity. Breast lesions were successfully localized and removed in all patients. Pathological findings revealed breast carcinoma in 11/39 patients (28%) and benign lesions in 28 (72%). Axillary SLNs were detected in 31/39 (79.5%) patients. The metastatic involvement of SLN was only seen in two cases. While the identification rate of the SNOLL technique performed with an intratumoral injection of 99mTc-NC as the sole radiotracer in non-palpable breast lesions was great, it was not fully satisfactory in SLNs.

Concordancia entre SPECT portátil y la gammagrafía convencional para detección de ganglio centinela en cáncer de mama

IntroductionFreehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning.The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). Materials and methodsOne hundred patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60–90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. ResultsThe observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). ConclusionFreehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.

The Relationship Between the Presence of Distal Collateral Lymphatic Flows and Obesity in Patients with Bilateral Lower Extremity Edema

Objective: This study aimed to comprehensively assess radionuclide imaging findings to aid in the clinical diagnosis of early-stage lower extremity lymphedema. Methods: Our retrospective study included 135 patients who underwent lymphoscintigraphy for bilateral lower extremity edema (BLEE) between 2017 and 2022. Of these patients, 117 (86.7%) were female. Lymphoscintigraphic images were acquired at the 10th, 40th, and 2nd hours post-injection of radiopharmaceuticals. Bilateral lower extremity lymphatic congestion (MLC) was observed in the 2nd-hour images of radionuclide imaging (RI), with an associated accumulation of activity in the inguinal lymph nodes. All patients presented with lower extremity edema. Results: Among our patients, 55 (40.7%) were classified as obese. Bilateral distal collateral flows (BDCF) were identified in 60 (44.4%) of our patients, all of whom were female. Within this group, 13 (21.7%) were obese, and 11 (18.3%) exhibited distal and direct muscle lymphatic congestion (DDMLC). DDMLC was present in 63 (46.7%) patients. Unilateral distal collateral flow (UDCF) was detected in 75 (55.6%) of the patients with BLEE, with 67 (89.3%) of them being obese. Obese patients exhibited a significantly higher prevalence of both UDCF and DDMLC (p: 0.0005). Detailed results can be found in Table 1-4 and Figures 3 and 4. Conclusion: Functional bilateral radionuclide imaging methods provide valuable data for physicians, enabling bilateral and comparative assessments. However, particular attention should be paid to the interpretation of asymmetric images, especially in specific patient groups.

La linfogammagrafía in vivo de los tumores del seno nasal identifica el ganglio retrofaríngeo y el nivel I como ganglios centinela predominantes

ObjectiveTo evaluate by in vivo lymphoscintigraphy and SPECT-CT imaging, the lymphatic drainage patterns of para-nasal sinus (PNS) tumours. To confirm or refute the belief of the retropharyngeal lymph node (RPLN) being the significant draining lymph node for such tumours. MethodsProspective cohort study conducted on previously untreated PNS tumours with no clinico-radiological evidence of lymph node metastasis. Lymphoscintigraphy undertaken by nasal endoscopic assisted peritumoral injection of 99mTc sulphur colloid. Injections were classified as anterior or posterior as per a vertical line along the maxillary sinus ostium. ResultsSeventeen patients were included. Lymphoscintigraphy successfully identified 17 sentinel nodes in 15 patients and was unsuccessful (lymphoscintigraphy failure) in 2 patients. Predominant sites of sentinel lymphatic drainage were noted to be the RPLN (n=8; 47%) and level I (n=7; 42%). Occasional drainage was identified at the peri-parotid node (n=1) and at level II (n=1). Contralateral drainage was noted in 2 patients (level I-1 and RPLN-1).Anterior injections drained predominantly to level I (6/8) and RPLN (2/8), while posterior injections drained predominantly to the RPLN (6/7). The relative risk of RPLN being identified as the sentinel node was significantly higher for posteriorly placed injections than for anteriorly placed injections (RR: 3.43; 95% CI: 1.0-11.8; P=.05). ConclusionThe RPLN is noted as a frequent draining node for sino-nasal tumours and merits routine attention in all sino-nasal tumours. The radio-colloid SPECT-CT technique described here offers an excellent in vivo technique to further explore and validate the lymphatic drainage pathways of these tumours.

In-vivo lymphoscintigraphy of sinonasal tumors identifies retropharyngeal node and level I as predominant sentinel nodes

ObjectiveTo evaluate by in- vivo lymphoscintigraphy and SPECT-CT imaging, the lymphatic drainage patterns of para-nasal sinus(PNS) tumors. To confirm or refute the belief of the retropharyngeal lymph node (RPLN) being the significant draining lymph node for such tumors. MethodsProspective cohort study conducted on previously untreated PNS tumors with no clinico-radiological evidence of lymph node metastasis. Lymphoscintigraphy undertaken by nasal endoscopic assisted peritumoral injection of 99mTc Sulfur colloid. Injections were classified as anterior or posterior as per a vertical line along the maxillary sinus ostium. Results17 patients were included. Lymphoscintigraphy successfully identified 17 sentinel nodes in 15 patients and was unsuccessful (lymphoscintigraphy failure) in 2 patients. Predominant sites of sentinel lymphatic drainage were noted to be the RPLN (n = 8; 47%), and Level I (n = 7; 42%). Occasional drainage was identified at the peri-parotid node(n = 1) and at Level II (n = 1). Contralateral drainage was noted in 2 patients (level I-1 and RPLN-1).Anterior injections drained predominantly to Level I (6/8) and RPLN (2/8), while posterior injections drained predominantly to the RPLN ( 6/7). The relative risk of RPLN being identified as the sentinel node was significantly higher for posteriorly placed injections than for anteriorly placed injections (RR- 3.43; 95% CI-1.0-11.8, p = 0.05). ConclusionThe RPLN is noted as a frequent draining node for sino-nasal tumours and merits routine attention in all sino-nasal tumors. The radio-colloid SPECT-CT technique described here offers an excellent in-vivo technique to further explore and validate the lymphatic drainage pathways of these tumours.

Pneumatic Compression-Assisted Lymphoscintigraphy for Quantitative Evaluation of Breast Cancer-Related Lymphedema.

Acquired lymphedema of upper extremity is a chronic pathologic status that frequently occurs after breast cancer treatment. Reliable and quantitative evaluation of lymphedema is crucial for successful management of patients. Although lymphoscintigraphy is the primary investigation for the confirmation and evaluation of lymphedema, the specific protocol of stress intervention is not well established. This study aims to introduce intermittent pneumatic compression (IPC) as a part of stress lymphoscintigraphy and compare the effectiveness of conventional stress lymphoscintigraphy (CSL) and pneumatic compression-assisted lymphoscintigraphy (PCAL). Our study was designed as a retrospective analysis of 85 breast cancer patients with lymphedema who underwent lymphoscintigraphy utilizing either IPC device or conventional stress maneuver and received complex decongestive therapy. The flow extent of the lymphatic fluid (FE) was evaluated using a 0- to 4-point scale based on lymphoscintigraphic images. The visualization of lymph nodes was also assessed. The clinical outcomes were evaluated by changes in side-to-side circumferential and volume differences of upper extremities and compared between groups. Of 85 patients, 47 underwent CSL, and 38 underwent PCAL. Participants with relatively preserved flow extent of the lymphatic fluid (FE 3) showed a significant difference in percentage reduction of volume (PRV) between CSL and PCAL groups ( P = 0.036). In the other groups, CSL and PCAL demonstrated comparable differences in PRV without statistical significance. Our study suggests that participants in the PCAL group with relatively preserved lymphatic flow extent (FE 3) had better PRV compared with those in the CSL group. The use of IPC devices in lymphoscintigraphy with the novel stress maneuver can help in the quantitative description of lymphedema status and the selection of an appropriate treatment method.

Evaluation of clinical efficacy of tumor necrosis factor‑α inhibitors in treatment of distal extremity swelling with pitting edema in psoriatic arthritis of inadequate response to conventional therapy: A 10‑year retrospective study.

Distal extremity swelling with pitting edema in psoriatic arthritis (PsA) is a rare rheumatological condition, whose management presents a challenge. The aim of the present study was to identify the clinical characteristics of, and formulate a standardized management strategy for, patients with distal extremity swelling with pitting edema in PsA. The medical records of consecutive patients with PsA, with or without distal extremity swelling with pitting edema, were systematically analyzed over a ~10-year period (between September 2008 and September 2018) in a single center and a comprehensive review (pathogenic mechanisms, clinical manifestations, and treatments) was undertaken. A total of 167 patients with PsA were evaluated, and distal extremity swelling with pitting edema was recorded in 16 of these patients. In three of the 16 patients, distal extremity swelling with pitting edema occurred as the first, isolated manifestation of PsA. The upper and lower extremities were affected, predominantly asymmetrically. Female patients with PsA were more likely to be affected with pitting edema and the blood test results revealed that the patients with PsA and pitting edema also presented with a significantly higher erythrocyte sedimentation rate and concentration of C-reactive protein. The onset of pitting edema was associated with the activity of the disease. Lymphoscintigraphy and magnetic resonance imaging (MRI) scans revealed that edema might have resulted from inflammation of the tenosynovial structures. Furthermore, treatment with tumor necrosis factor-α inhibitor (TNFi) elicited improvements in patients with pitting edema that were not responsive to conventional synthetic disease-modifying antirheumatic drug therapy. In conclusion, distal extremity swelling with pitting edema, also termed atypical remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome, may represent the initial isolated manifestation of PsA. The atypical RS3PE syndrome in PsA was attributable to inflammation of the tenosynovial structures, and TNFi may serve as a potential treatment.

Within-patient comparison between [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy and [99mTc]Tc-tilmanocept lymphoscintigraphy for sentinel lymph node detection in oral cancer: a pilot study

To compare sentinel lymph node (SLN) identification using [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy to [99mTc]Tc-tilmanocept lymphoscintigraphy (including SPECT/CT) in early-stage oral cancer. Furthermore, to assess whether reliable intraoperative SLN localization can be performed with a conventional portable gamma-probe using [99mTc]Tc-tilmanocept without the interference of [68Ga]Ga-tilmanocept in these patients. This prospective within-patient comparison pilot study evaluated SLN identification by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy compared to conventional lymphoscintigraphy using [99mTc]Tc-tilmanocept (~ 74MBq) in 10 early-stage oral cancer patients scheduled for SLN biopsy. After conventional [99mTc]Tc-tilmanocept lymphoscintigraphy, patients underwent peritumoral administration of [68Ga]Ga-tilmanocept (~ 10MBq) followed by PET/CT acquisition initiated 15min after injection. Intraoperative SLN localization was performed under conventional portable gamma-probe guidance the next day; the location of harvested SLNs was correlated to both lymphoscintigraphic images in each patient. A total of 24 SLNs were identified by [99mTc]Tc-tilmanocept lymphoscintigraphy, all except one were also identified by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy. [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy identified 4 additional SLNs near the injection site, of which two harbored metastases. Lymphatic vessels transporting [68Ga]Ga-tilmanocept were identified by PET/CT lymphoscintigraphy in 80% of patients, while draining lymphatic vessels were visualized by [99mTc]Tc-tilmanocept lymphoscintigraphy in 20% of patients. Of the 33 SLNs identified by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy, 30 (91%) were intraoperatively localized under conventional gamma-probe guidance. [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy provided more accurate identification of SLNs and improved visualization of lymphatic vessels compared to [99mTc]Tc-tilmanocept lymphoscintigraphy. When combined with peritumoral administration of [99mTc]Tc-tilmanocept, SLNs detected by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy can be reliably localized during surgery under conventional gamma-probe guidance.

Analysis of the Different Lymphatic Drainage Patterns during Sentinel Lymph Node Biopsy for Skin Melanoma

In the last two decades, studies of lymphoscintigraphy imaging in lymphatic mapping reported an extreme heterogeneity of skin lymphatic drainage of some skin area, in contrast with the previous scientific literature. The aim of this study was to investigate the presence of any correlations between the topographical location of cutaneous melanoma and the topographical location of sentinel lymph nodes. Data from 165 patients undergoing sentinel lymph node biopsy between January 2013 and May 2021 were analyzed, demonstrating that melanomas in the Lumbar region presented a significant more heterogeneous drainage by site than those in the Scapular region (p < 0.01) and that melanomas in the Subscapular region were significantly more heterogeneous by laterality (unilateral vs. bilateral) than those in the Scapular region (p < 0.05). Results of this study supported the evidence of multiple lymphatic drainage as regards the sentinel node biopsy performed in skin melanoma located on the dorsal subscapular region and lumbar region. For this reason, the association of preoperative lymphoscintigraphy with another imaging evaluation is needed in these critical cutaneous areas. Recent technical developments enabling fluorescence lymphography together with indocyanine green have significantly improved the visualization of lymphatic drainage patterns at a microscopic level. In the preoperative phase, any doubt can be resolved by associating the SPET-CT scan to lymphoscintigraphy, while during the intraoperative phase, an additional evaluation with indocyanine green can be performed in doubtful cases. The aim of the duplex lymphatic mapping (pre and/or intraoperative) is an accurate search of sentinel nodes, in order to reduce the rate of false negatives.

Lymphedema in Breast Cancer

Forearm edema in breast cancer is caused by disruption of the axillary lymphatic system by surgery or radiotherapy, which causes fluid accumulation in the subcutaneous tissue of the arm, with decreased distensibility of the tissues around the joints and increased weight of the extremities. Risk factors with strong clinical evidence include extensive surgery (eg, axillary lymph node dissection, more dissection of lymph nodes, mastectomy) and being overweight or obese. A BMI greater than or equal to 30 kg / m2 is an independent risk factor for lymphedema associated with breast cancer. Subclinical edema and cellulitis in the literature have also been cited as risk factors for lymphedema associated with breast cancer. The mechanism underlying lymphedema is dysfunction in the lymphatic transport system. of interstitial pressure. Lymphatic fluid, known as lymph, is drained by blind-ended lymphatic capillaries. It is then filtered through the lymph nodes and eventually re-enters the circulatory system, through the thoracic duct, where peripheral venous blood enters the right atrium of the heart. Under normal conditions, the same amount is transported to the interstitial as is transported from the interstitial, a balance that is disturbed in lymphedema due to reduced lymph transport capacity, leading to fluid accumulation and swelling. Options include bioelectrical impedance analysis (BIA), band measurement, perometry, and water displacement. Lymphoscintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI) can also be used to describe lymphatic dysfunction. Management of lymphedema associated with breast cancer conservatively with controlled and operative compression therapy with resection, microsurgery, tissue transfer and liposuction

Regional lymph node metastases in cutaneous melanoma: a single-center analysis from southeast europe

Sentinel lymph node biopsy is the standard of care for nodal staging in clinically node-negative melanoma patients. Our goal was to present 10-year results of sentinel lymph node biopsy at our institution and to evaluate the clinicopathologic factors as potential predictors of sentinel lymph node and non-sentinel lymph node metastatic involvement in patients with cutaneous melanoma. We have analyzed clinicopathologic and lymphoscintigraphic characteristics in 420 patients with cutaneous melanoma who underwent sentinel lymph node biopsy between 2010 and 2019. In addition, we have examined the results of group of patients with positive sentinel lymph node biopsy undergoing complete lymph node dissection. The overall detection rate of sentinel lymph node biopsies was 97.1%, of which 18.8% was metastatic. Drainage to one regional basin was seen in 345 patients (83.1%) and to multiple drainage regions in 71 patients (17%). In-transit lymph nodes were detected in 20 patients. On univariate logistic regression analysis, male gender, primary tumor thickness with nodular histology, acral location, presence of ulceration, and the number of nodes harvested were significantly associated with sentinel lymph node biopsy status (p < 0.05). On multivariate analysis, the Breslow thickness was the only independent predictor of sentinel lymph node biopsy status. The metastases in non-sentinel lymph node found in 26 patients with positive sentinel lymph node (35.6%) correlated on univariate, as well as on multivariate logistic regression, with tumor subtype and number of sentinel lymph node harvested. In addition to the well-established primary tumor thickness as a predictor of sentinel lymph node biopsy positivity, we observed acral location and nodular melanoma subtype to significantly enhance the risk of metastases in sentinel lymph node(s). Primary tumor histology and number of nodes harvested were the only statistically significant variables predicting the non-sentinel lymph node status on multivariate analysis. Lymphoscintigraphy imaging characteristics were not significantly associated with sentinel lymph node status.

The Effects of Modified Lymphoscintigraphy Techniques on Sentinel Lymph Node Biopsy Success During the COVID-19 Pandemic Period

Background and objective Sampling of the sentinel lymph node (SLN) in breast cancer provides accurate information about the condition of the axilla in 95% of cases. Technically in detecting SLN; radioactive substance, dyers or both are used. During the COVID-19 (Coronavirus disease 2019) pandemic, delayed images were not taken in lymphoscintigraphy to reduce the risk of transmission by shortening the waiting time in our center. In this study, the effects of early and delayed lymphoscintigraphic images and only early images on our clinical practice were evaluated. Methods We investigated the data of 147 patients in this study who underwent SLNB due to early-stage breast cancer at our institute during the COVID-19 pandemic period (PP) (March/April/May 2020) and within 3 months before the pandemic were evaluated. Results Patients were divided into two groups, before pandemic (BP) and PP. BP consisted of patients whose early and delayed images were taken in lymphoscintigraphy whereas PP consisted of those with early images only. There were 74 patients in the BP group and 73 patients in the PP group. Early phase increased uptake was not observed in 23 patients, and increased uptake was obtained from 22 of these patients with delayed imaging in BP period. In PP, increased uptake was not observed in 12 patients. SLN was not detected in 2 patients in the BP group and 7 in the PP group. It was found that the sensitivity, NPV and accuracy of the SLNB procedure performed after taking delayed images was higher. Conclusions In the present study, we believe that if technically possible, delayed images taken during the lymphoscintigraphy can assist the surgeon in terms of SLN detection and the number of SLNs removed.

New Developments in Imaging for Sentinel Lymph Node Biopsy in Early-Stage Oral Cavity Squamous Cell Carcinoma.

Simple SummaryIn early-stage (cT1-2N0) oral cancer, occult lymph node metastases are present in 20–30% of patients. Accordingly, accurate staging of the clinically negative cervical nodal basin is warranted in these patients. Sentinel lymph node biopsy has proven to reliably stage the clinically negative cervical nodal basin in early-stage oral cancer. However, due to the limited resolution of conventional sentinel lymph node imaging, occult lymph node metastasis may be missed in particular circumstances. Therefore, technical developments are necessary to bring the diagnostic accuracy of sentinel lymph node biopsy, in early-stage oral cancer, to a higher level. This review evaluates novel sentinel lymph node imaging techniques for early-stage oral cancer, such as MR lymphography, CT lymphography, PET lymphoscintigraphy and contrast-enhanced lymphosonography. Their reported diagnostic accuracy is described and their relative merits, disadvantages and potential applications are outlined.Sentinel lymph node biopsy (SLNB) is a diagnostic staging procedure that aims to identify the first draining lymph node(s) from the primary tumor, the sentinel lymph nodes (SLN), as their histopathological status reflects the histopathological status of the rest of the nodal basin. The routine SLNB procedure consists of peritumoral injections with a technetium-99m [99mTc]-labelled radiotracer followed by lymphoscintigraphy and SPECT-CT imaging. Based on these imaging results, the identified SLNs are marked for surgical extirpation and are subjected to histopathological assessment. The routine SLNB procedure has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). However, an infamous limitation arises in situations where SLNs are located in close vicinity of the tracer injection site. In these cases, the hotspot of the injection site can hide adjacent SLNs and hamper the discrimination between tracer injection site and SLNs (shine-through phenomenon). Therefore, technical developments are needed to bring the diagnostic accuracy of SLNB for early-stage OSCC to a higher level. This review evaluates novel SLNB imaging techniques for early-stage OSCC: MR lymphography, CT lymphography, PET lymphoscintigraphy and contrast-enhanced lymphosonography. Furthermore, their reported diagnostic accuracy is described and their relative merits, disadvantages and potential applications are outlined.

Sentinel lymph node detection in oral cancer: a within-patient comparison between [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid

PurposeSentinel lymph node (SLN) biopsy has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). [99mTc]Tc-tilmanocept may be of benefit in OSCC with complex lymphatic drainage patterns and close spatial relation to SLNs.MethodsA prospective within-patient evaluation study was designed to compare [99mTc]Tc-tilmanocept with [99mTc]Tc-nanocolloid for SLN detection. A total of 20 patients with early-stage OSCC were included, who underwent lymphoscintigraphy with both tracers. Both lymphoscintigraphic images of each patient were evaluated for SLN detection and radiotracer distribution at 2–4 h post-injection.ResultsThe injection site’s remaining radioactivity was significantly lower for [99mTc]Tc-tilmanocept (29.9%), compared with [99mTc]Tc-nanocolloid (60.9%; p < 0.001). Radioactive uptake in SLNs was significantly lower for [99mTc]Tc-tilmanocept (1.95%) compared with [99mTc]Tc-nanocolloid (3.16%; p = 0.010). No significant difference was seen in SLN to injection site ratio in radioactivity between [99mTc]Tc-tilmanocept (0.066) and [99mTc]Tc-nanocolloid (0.054; p = 0.232). A median of 3.0 and 2.5 SLNs were identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.297). Radioactive uptake in higher echelon nodes was not significantly different between [99mTc]Tc-tilmanocept (0.57%) and [99mTc]Tc-nanocolloid (0.86%) (p = 0.052). A median of 2.0 and 2.5 higher echelon nodes was identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.083).Conclusion[99mTc]Tc-tilmanocept had a higher injection site clearance, but at the same time a lower uptake in the SLN, resulting in an SLN to injection site ratio, which was not significantly different from [99mTc]Tc-nanocolloid. The relatively low-radioactive uptake in SLNs of [99mTc]Tc-tilmanocept may limit intraoperative detection of SLNs, but can be overcome by a higher injection dose.

Lymphoscintigraphic Abnormalities Associated with Milroy Disease and Lymphedema-Distichiasis Syndrome.

Background: Primary lymphedema is genetically heterogeneous. Two of the most common forms of primary lymphedema are Milroy disease (MD) and lymphedema-distichiasis syndrome (LDS). This study aims to look further into the pathogenesis of the two conditions by analyzing the lymphoscintigram images from affected individuals to ascertain if it is a useful diagnostic tool. Methods and Results: The lymphoscintigrams of patients with MD and LDS were analyzed, comparing the images and transport parameters of the two genotypes against a control population. Lymphoscintigrams were available for 12 MD and 16 LDS patients (all genetically proven diagnoses). Eight of the 12 (67%) lymph scans performed on patients with MD demonstrated little or no uptake from the initial lymphatics and poor visualization of the inguinal lymph nodes. These changes were consistent with a "functional aplasia," that is, the lymphatic vessels were present but appeared to be ineffective in absorbing the interstitial fluid into the lymphatic system. In patients with LDS the lymphoscintigraphic appearances were different. In 12 of the 16 scans (75%), the lymph scans were highly suggestive of lymphatic collector reflux. Quantification revealed a significantly reduced uptake of tracer within the inguinal lymph nodes and a higher residual activity in the feet at 2 hours in MD compared with LDS and compared with controls. Conclusion: Lymphoscintigraphic imaging and quantification can be characteristic in specific genetic forms of primary lymphedema and may be useful as an additional tool for in-depth phenotyping, leading to a more accurate diagnosis and providing insight into the underlying mechanism of disease.

Assessment of Nonradioactive Multispectral Optoacoustic Tomographic Imaging With Conventional Lymphoscintigraphic Imaging for Sentinel Lymph Node Biopsy in Melanoma

The metastatic status of sentinel lymph nodes (SLNs) is the most relevant prognostic factor in breast cancer, melanoma, and other tumors. The conventional standard to label SLNs is lymphoscintigraphy with technetium Tc 99m. A worldwide shortage and known disadvantages of Tc 99m have intensified efforts to establish alternative, nonradioactive imaging techniques. To assess a new nonradioactive method using multispectral optoacoustic tomographic (MSOT) imaging in comparison with conventional lymphoscintigraphic imaging for SLN biopsy (SLNB) in melanoma. Analysis of a cross-sectional study was conducted at the University Hospital-Essen, Skin Cancer Center, Essen, Germany. Between June 2, 2014, and February 22, 2019, 83 patients underwent SLNB with an additional preoperative indocyanine green (ICG) application. Sentinel lymph node basins were preoperatively identified by MSOT imaging, and ICG-labeled SLNs were intraoperatively detected using a near-infrared camera. The surgeons were blinded to the lymphoscintigraphic imaging results in the beginning of the SLNB. Use of a γ probe was restricted until the SLNB procedure was attempted by the nonradioactive method. Concordance of SLN basins and SLNs identified by MSOT imaging plus near-infrared camera vs lymphoscintigraphic imaging plus single-photon emission computed tomographic or computed tomographic imaging was assessed. Of the 83 patients (mean [SD] age, 54.61 [17.53] years), 47 (56.6%) were men. In 83 surgical procedures, 165 SLNs were excised. The concordance rate of ICG-labeled and Tc 99m-marked detected SLN basins was 94.6% (n = 106 of 112). Intraoperatively, 159 SLNs were detected using a near-infrared camera and 165 were detected by a γ probe, resulting in a concordance rate of 96.4%. Multispectral optoacoustic tomographic imaging visualized SLNs in all anatomic regions with high penetration depth (5 cm). The findings of this study suggest that nonradioactive SLN detection via MSOT imaging allows identification of SLNs at a frequency equivalent to that of the current radiotracer conventional standard. Multispectral optoacoustic tomographic imaging appears to be a viable nonradioactive alternative to detect SLNs in malignant tumors.

Indocyanine Green Fluorescence Imaging with Lymphoscintigraphy for Sentinel Node Biopsy in Melanoma: Increasing the Sentinel Lymph Node-Positive Rate.

The goal of this study was to analyze patients who underwent a sentinel lymph node biopsy (SLNB) in melanoma with the combination of radioisotope lymphoscintigraphy and indocyanine green (ICG) fluorescence imaging to compare our true positive (TP) rate, a means to perform immediate analysis of the SLNB, with that of the literature. Consecutive cutaneous melanoma patients who underwent SLNB with lymphoscintigraphy and ICG-based fluorescence imaging by the senior author (BG) from 2012 to 2018 were prospectively enrolled. The average expected SLN-positive rate per T stage was calculated based on three studies and compared with our SLN-positive rate. Overall, 574 consecutive patients were analyzed. Average Breslow thickness was 1.9mm. A total of 1754 sentinel nodes were sampled; 1497 were identified by gamma probe signaling and ICG, 241 were identified by gamma probe signaling only, and 16 were identified by ICG only. There were 123 (21.4%) patients with at least one positive SLN; 113 (91.9%) had at least one positive node identified with both gamma probe signaling and ICG, 8 (6.5%) had positive node(s) identified with gamma probe signaling only, and 2 (1.6%) had positive node(s) identified with ICG only. There was an overall 21.4% SLN-positive rate, with 8% T1, 18.5% T2, 41.1% T3, and 52.4% T4, which is higher than the predicted rates for each stage. With the largest cohort of patients reported who underwent a melanoma SLNB with lymphoscintigraphy and ICG, we demonstrated that this technique results in higher SLN-positive rates than predicted. Patients are being followed but, given the TP data, knowledge of our results may foster the use of this modality to improve staging and treatment options.

Perioperative PET/CT lymphoscintigraphy and fluorescent real-time imaging for sentinel lymph node mapping in early staged colon cancer

PurposeUsing current optical imaging techniques and gamma imaging modalities, perioperative sentinel lymph node (SLN) identification in colon cancer can be difficult when the SLN is located near the primary tumour or beneath a thick layer of (fat) tissue. Sentinel lymph node mapping using PET/CT lymphoscintigraphy combined with real-time visualization of the SLN using near-infrared imaging has shown promising results in several types of cancer and may facilitate the successful identification of the number and location of the SLN in early colon cancer.MethodsClinical feasibility of PET/CT lymphoscintigraphy using preoperative endoscopically injected [89Zr]Zr-Nanocoll and intraoperative injection of the near-infrared (NIR) tracer Indocyanine Green (ICG) was evaluated in ten early colon cancer patients. Three preoperative PET/CT scans and an additional ex vivo scan of the specimen were performed after submucosal injection of [89Zr]Zr-Nanocoll. All SLNs and other lymph nodes underwent extensive pathological examination for metastases. A histopathological proven lymph node visible at preoperative PET/CT and identified at PET/CT of the specimen was defined as SLN.ResultsA total of 27 SLNs were harvested in seven out of eight patients with successful injection of both tracers. In one patient no SLNs were assigned preoperatively. In two patients injection of [89Zr]Zr-Nanocoll failed due to incorrect needle positioning. Twenty-one (78%) SLNs were found intraoperatively using NIR-imaging. Eleven of the 27 (41%) SLNs were located near the primary tumour (< 2 cm). Those six SLNs not found intraoperatively with NIR-imaging were all located close to the tumour. In all seven patients at least one SLN could be assigned at preoperative imaging 24 h after tracer administration. One SLN contained metastases detected by immunohistochemistry. No metastases were found in the non-SLNs.ConclusionsThis study shows the potential of preoperative PET/CT lymphoscintigraphy to inform the surgeon about the number and location of SLNs in patients with early colon cancer. The additional use of NIR-imaging allows for intraoperative identification of these SLNs which are invisible with conventional white light imaging. Further research is necessary to improve and simplify the technique. We recommend perioperative SLN identification using a preoperative lymphoscintigraphy scan just before surgery approximately 24 h after injection. Additionally a postoperative scan of the specimen combined with intraoperative real-time NIR-imaging should be performed.