Diagnosis Of Sentinel Lymph Node Research Articles

ThP2.3 - Fluorescein Sodium - An Alternative to Methylene Blue In Detecting Sentinel Axillary Lymph Node In Carcinoma Breast

Abstract Aim To ascertain the validity of fluorescein sodium in the identification of SLN in patients with Breast carcinoma. Material and Methods A Prospective Observational study was conducted among 30 patients with carcinoma breast aged >18 years with no clinically identifiable axillary lymph nodes at the Department of General Surgery at a single centre, in rural India over period of 2 year. Institutional Ethical clearance was obtained prior to the start of the study and Informed consent was obtained from all the patients recruited Results Mean age was 53.13 ± 14.180 years. The majority of subjects were in the age group 51 to 60 years (26.7%). 20% were in stage T2N0M0, 30% were in T3N0M0 and 50% were in T4BN0M0. on HPE 86.7% had Infiltrating Ductal Ca, 10% had Lobular Ca and 3.3% had Squamous Cell Ca. Fluorescein Dye staining had a sensitivity of 84.21%, specificity was 30.99%, Positive Predictive Value was 39.51%, Negative Predictive Value was 78.57% and Diagnostic Accuracy was 49.54% in comparison with HPE. Methylene Blue staining had a sensitivity of 44.74%, specificity was 35.21%, Positive Predictive Value was 26.98%, Negative Predictive Value was 54.35% and Diagnostic Accuracy was 38.53% in comparison with HPE. Conclusion From the study findings it can be concluded that the detection of SLNs using fluorescein was high compared to methylene blue, both methods were feasible and safe in patients with breast carcinoma. Fluorescein dye had better validity in the diagnosis of Sentinel lymph node compared to Methylene blue in the Carcinoma of the breast.

Viability of Whole-Slide Imaging for Intraoperative Touch Imprint Cytological Diagnosis of Axillary Sentinel Lymph Nodes in Breast Cancer Patients.

Whole-slide imaging (WSI) is a promising tool in pathology. However, the use of WSI in cytopathology has lagged behind that in histology. We aimed to evaluate the utility of WSI for the intraoperative touch imprint cytological diagnosis of axillary sentinel lymph nodes (SLNs) in breast cancer patients. Glass slides from touch imprint cytology of 480 axillary SLNs were scanned using two different WSI scanners. The intra- and interobserver concordance, accuracy, possible reasons for misdiagnosis, scanning time, and review time for three cytopathologists were compared between WSI and light microscopy (LM). A total of 4320 diagnoses were obtained. There was substantial to strong intraobserver concordance when comparing reads among paired LM slides and WSI digital slides (κ coefficient ranged from 0.63 to 0.88, and concordance rates ranged from 94.58% to 98.33%). Substantial to strong interobserver agreement was also observed among the three cytopathologists (κ coefficient ranged from 0.67 to 0.85, and concordance rates ranged from 95.42% to 97.92%). The accuracy of LM was slightly higher (average of 98.06%) than that of WSI (averages of 96.81% and 97.78%). The majority of misdiagnoses were false negative diagnoses due to the following top three causes: few cancer cells, confusing cancer cells with histiocytes, and confusing cancer cells with lymphocytes. This study is the first to address the feasibility of WSI in touch imprint cytology. The use of WSI for intraoperative touch imprint cytological diagnosis of SLNs is a practical option when experienced staff are not available on-site.

Establishing guidelines for sentinel lymph node ultrastaging in endometrial cancer

BackgroundMany sentinel lymph node (SLN) ultrastaging protocols for endometrial cancer exist, but there is no consensus method.ObjectiveThis study aims to develop guidelines for size criteria in SLN evaluation for endometrial...

Multimodal ultrasound imaging: a method to improve the accuracy of sentinel lymph node diagnosis in breast cancer.

This study assessed the utility of multimodal ultrasound in enhancing the accuracy of breast cancer sentinel lymph node (SLN) assessment and compared it with single-modality ultrasound. Preoperative examinations, including two-dimensional ultrasound (2D US), intradermal contrast-enhanced ultrasound (CEUS), intravenous CEUS, shear-wave elastography (SWE), and surface localization, were conducted on 86 SLNs from breast cancer patients. The diagnostic performance of single and multimodal approaches for detecting metastatic SLNs was compared to postoperative pathological results. Among the 86 SLNs, 29 were pathologically diagnosed as metastatic, and 57 as non-metastatic. Single-modality ultrasounds had AUC values of 0.826 (intradermal CEUS), 0.705 (intravenous CEUS), 0.678 (2D US), and 0.677 (SWE), respectively. Intradermal CEUS significantly outperformed the other methods (p<0.05), while the remaining three methods had no statistically significant differences (p>0.05). Multimodal ultrasound, combining intradermal CEUS, intravenous CEUS, 2D US, and SWE, achieved an AUC of 0.893, with 86.21% sensitivity and 84.21% specificity. The DeLong test confirmed that multimodal ultrasound was significantly better than the four single-modal ultrasound methods (p<0.05). Decision curve analysis and clinical impact curves demonstrated the superior performance of multimodal ultrasound in identifying high-risk SLN patients. Multimodal ultrasound improves breast cancer SLN identification and diagnostic accuracy.

Frozen section versus imprint cytology for evaluation of intraoperative sentinel lymph node biopsy in breast cancer patients: a prospective study

Background Currently, two methods are commonly used for intraoperative examination of the sentinel lymph nodes (SLNs) biopsy in breast cancer (BC); imprint cytology (IC) and frozen section (FS). Aim Assessing the outcomes of the intraoperative SLN IC evaluation and comparing them to those of FS. Methods Eighty-seven patients have been diagnosed with T1-T2 BC. Sentinel nodes were detected using the blue dye injection technique intraoperatively. From each SLN, two slides of touch imprint were provided for imprint cytology evaluation and excised SLNs were then sent for frozen section. Results Histological examination of SLNs revealed 10 positive cases and 77 negative cases. Regarding IC, positive SLNs were detected in 8 cases and 79 case showed negative results. For FS, positive SLNs were detected in 11 case and 76 case were negative. Regarding IC, the sensitivity and specificity were 60% and 97.4%, respectively, whereas the sensitivity and specificity reach 90% and 97.4% for FS. Overall accuracy was 93.1% for IC and 96.6% for FS. Conclusion Intraoperative SLN diagnosis by imprint cytology in many aspects, could be comparable to that obtained from FS examination. Imprint cytology is simple, fast, easily performed, inexpensive, and highly accurate way of intraoperative SLN diagnosis in BC patients.

Diagnosis of sentinel lymph nodes in patients with cancer of the larynx and laryngopharynx using a new radiopharmaceutical based on technetium-99m-labeled gamma aluminum oxide

Аim. To study the possibility of using a radiopharmaceutical based on aluminum oxide labeled with 99mТс ([99mТс]-Al2O3) for the diagnosis of sentinel lymph nodes (SLN) in tumors of the larynx and laryngopharynx in comparison with a phytate colloid ([99mTc]-phytate colloid).Materials and methods. The study included patients with cancer of the larynx and laryngopharynx (T2–4N0M0) (n = 54). In the prospective group (n = 30), [99mТс]-Al2O3 was used as a radiopharmaceutical, in the retrospective group (n = 24), [99mТс]-phytate colloid was used. All radiopharmaceuticals were introduced endoscopically into the submucosal space along the periphery of the tumor. After 18 hours, single-photon emission computed tomography (SPECT) and intraoperative SLN detection were performed.Results. In the retrospective group, SLNs were detected in 20 out of 24 patients. A total of 32 lymph nodes were identified in the retrospective group. The median number of detected lymph nodes in one patient was 1.3 [0–3], the intensity of the radiopharmaceutical uptake on scintigrams was 2.2 [0.7–8.1], intraoperatively – 4 [1.6–9.0]. In the prospective group, [99mTc]-Al2O3 uptake in the lymph nodes of the neck was determined in 27 patients (90%); in3 patients, SLNs were not visualized. A total of 57 lymph nodes were identified (in 27 patients). The median number of visualized SLNs was 1.5 [0–5], the intensity of [99mТс]-Al2O3 uptake according to SPECT and intraoperative detection was 4.8 [0.7–19.4] and 6 [1.1–22.0], respectively.Conclusion. The most significant advantage of using [99mТс]-Al2O3 as a radiopharmaceutical is its high uptake in SLNs, which leads to an increase in the sensitivity of the method as a whole up to 90 versus 83% when using [99mTc]-phytate colloid.

Sentinel lymph node diagnosis in mammary tumors of canines using computed tomography: Indirect lymphangiography

Sentinel lymph node diagnosis in mammary tumors of canines using computed tomography: Indirect lymphangiography

Contrast-enhanced lymphatic US can improve the preoperative diagnostic performance for sentinel lymph nodes in early breast cancer.

ObjectivesTo evaluate the preoperative diagnostic value of contrast-enhanced lymphatic ultrasound (CEUS) for the sentinel lymph node (SLN) status in early breast cancer.Materials and methodsWe prospectively recruited 102 consecutive patients with clinically node-negative early breast cancer from July 2021 to October 2021. All patients underwent conventional US and percutaneous CEUS examinations. The CEUS of SLNs were classified into four enhancement patterns: homogeneous (I), featured inhomogeneous (II), focal defect (III), and no enhancement (IV). The diagnostic performance of conventional US and CEUS for SLN metastasis was assessed by receiver operating characteristic (ROC) curves and decision curves.ResultsA total of 78 women were enrolled in this study, including 55, 18, and 5 patients with negative axilla, 1–2, and ≥ 3 metastastic SLNs pathologically, respectively. The identification rate of SLNs by CEUS was 100%. Patterns I and II can select 91.7% (44/48) of patients with disease-free axilla, while patterns III and IV had higher percentages of metastasis (65.2%, p < 0.001 and 57.1%, p < 0.002, respectively). For the SLN metastatic burden, 100% (48/48) of patients with pattern I/II had ≤ 2 metastatic SLNs. Compared with conventional US, the CEUS enhancement patterns showed significant improvement in diagnosing metastatic SLNs (0.813 vs 0.601, p < 0.001). CEUS had greater clinical benefits and correctly reclassified 48% of metastatic SLNs (p < 0.001) without sacrificing the classification accuracy of negative SLNs (p = 0.25), and could improve prediction accuracy by 0.42 (p < 0.001).ConclusionsCEUS demonstrated better diagnostic performance and greater clinical benefits than conventional US for the preoperative diagnosis of SLNs, showing its potential to select candidates for precluding axillary surgery in early breast cancer.Key Points• The homogeneous and featured inhomogeneous enhancement of SLNs are highly suggestive of negative LNs, while focal defect (p < 0.001) and no enhancement (p < 0.002) patterns had higher percentages of metastasis.• The proportion of SLNs with highly suspicious signs on conventional US increases as the type of enhancement pattern increases (no suspicious signs in pattern I/II, 34.8% in pattern III, and 85.7% in pattern IV).• Compared with conventional US, CEUS improved the area under the receiver operating characteristic curve (0.813 vs. 0.601, p < 0.001) and had greater clinical benefits (IDI = 0.42, p < 0.001) for the diagnosis of axillary metastasis.

ОСОБЕННОСТИ РАДИОНУКЛИДНОЙ ДИАГНОСТИКИ СИГНАЛЬНЫХ ЛИМФАТИЧЕСКИХ УЗЛОВ У БОЛЬНЫХ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ С ПОМОЩЬЮ НОВОГО ОТЕЧЕСТВЕННОГО РАДИОФАРМПРЕПАРАТА НА ОСНОВЕ ОКСИДА АЛЮМИНИЯ, МЕЧЕННОГО 99mТс

Purpose: To study the possibility of using [99mТс]-Al2O3 for the diagnosis of sentinel lymph nodes (SLN) in patients with breast cancer, to analyze the results obtained in comparison with a phytate colloid labeled with 99mTc. Material and methods: The study included 86 patients with breast cancer. [99mTc]-phytate colloid (31 patients) and [99mТс]-Al2O3 (55 patients) were used as radiopharmaceutical. Results: The optimal time interval between the injection of [99mТс]-Al2O3 and the acquisition of a scintigraphic image was determined to be 18-20 hours, when the maximum possible number of lymph nodes (LNs) with the most optimal level of radioactivity for their detection is visualized. In the group of patients who were injected with [99mTc]-phytate colloid, SLN were visualized in 27 out of 31 patients, a total of 37 LNs were detected in this group. The median number of detected LNs in one patient was 1 [0–3], the intensity of accumulation of [99mTc]-phytate colloid according to single-photon emission computed tomography (SPECT) was 1.75% [0.5–4.3%], intraoperatively using gamma -probe – 2.95% [1.1–5.6%]. When [99mТс]-Al2O3 was used as radiopharmaceutical, SLNs were detected in 51 patients out of 55. In total, 111 LNs were detected in this group, the median number of detected LNs in one patient was 2 [0-6], the intensity of accumulation of [99mТс]-Al2O3 according to SPECT data – 6.1% [0.5–18.4%], intraoperatively – 7.2% [1.3–22.1%]. In the absence of radiopharmaceuticals accumulation in regional LNs (n=7 in total), 3 patients had total metastatic lesions of the SLN, in two of them other regional LNs were also affected by metastases. Conclusion: A comparative analysis of the indices of two radiopharmaceuticals shows that studies with [99mТс]-Al2O3 are characterized by statistically significantly higher accumulation rates in the SLN compared with [99mTc]-phytate colloid. The number of detected LNs when using [99mТс]-Al2O3 was also higher than in the group with [99mTc]-phytate colloid. As a result, when [99mТс]-Al2O3 is used, the method is characterized by higher sensitivity in detecting SLN (94.5%).

Meta-Analysis of the Diagnostic Value of Tracer Staining Technology Based on Nanocarbon Suspension in Sentinel Lymph Node Biopsy of Breast Cancer.

Objective To evaluate the diagnostic value of the nanometer carbon suspension tracer staining technique in sentinel lymph node biopsy of breast cancer is the objective of this study. Methods The PubMed, Embase, Cochrane Library (Central), and Web of Science (SCI Expanded), and Chinese databases (CNKI, VIP, Wan Fang, and CBM) were systematically searched for studies on the diagnostic value of nanocarbon suspension in sentinel lymph node biopsy of breast cancer. Two reviewers independently assessed the methodological quality of each study using the QUADAS-2 tool. The extracted valid data were calculated using Meta-Disc1.4 software and tested for heterogeneity. STATA14.0 software was selected for sensitivity analysis of the included studies, and publication bias was assessed using Deeks' forest plot asymmetry test. Results A total of 10 studies were obtained. The pooled data were as follows: sensitivity, 0.92 (0.88~0.95); specificity, 0.99 (0.98~1.00); positive likelihood ratio, 69.24 (30.34~158.02); negative likelihood ratio, 0.09 (0.06~0.13); and the combined diagnostic odds ratio, 747.40 (285.77~1954.76), AUC = 0.9881. Nanocarbon suspension tracers have an accuracy rate of 98.81% in the diagnosis of sentinel lymph nodes in breast cancer. Conclusion Tracer staining technology based on nanocarbon suspension can accurately assess the status of lymph nodes in sentinel lymph node biopsy of breast cancer and has good stability and operability, which is worthy of clinical promotion.

Percutaneous contrast-enhanced ultrasound for localization and qualitative diagnosis of sentinel lymph nodes in cutaneous malignant melanoma of lower extremities: a preliminary study.

To explore the feasibility of sentinel lymph node (SLN) tracing by percutaneous contrast-enhanced ultrasound (pCEUS) in patients with cutaneous malignant melanoma (CMM) and the ability to enhance patterns of SLNs in diagnosing lymph nodes (LNs) metastases. Fifty-three patients with CMM of the lower extremities treated at our hospital were included in the study. All the participants received pCEUS preoperatively. The enhanced lymphatic channels (LCs) and associated SLNs were observed and tracked in real-time. The number of enhanced LCs and enhancing patterns of SLNs were recorded. Subsequently, SLNs localized by pCEUS were pathologically examined. Of the 53 cases, SLNs were successfully localized by pCEUS in 48 cases. In total, there were 59 detected SLNs averaging 1.23±0.42 SLNs per case. The main lymphatic drainage patterns (LDPs) were the following: one enhanced LC pointed to one or more than one SLN, and multiple enhanced LCs pointed to one or multiple SLNs. There were four enhancing patterns of SLNs (uniform, annular, uneven, and no enhancement), among which the first two were considered benign nodes, while the latter two were considered metastatic nodes. With pathological results as the gold standard, the diagnostic sensitivity and specificity by pCEUS were 90.9% and 75.0%, respectively. Contrast-enhanced ultrasound (US) is a feasible approach for SLN identification in patients with CMM of the lower extremities. Enhancing patterns of SLNs may help predict metastasizing SLNs. This novel method may be a promising technique for clinical application.

Contrast-Enhanced Ultrasound for Precise Sentinel Lymph Node Biopsy in Women with Early Breast Cancer: A Preliminary Study.

Background: Sentinel lymph node biopsy (SLNB), as a common method for axillary staging of early breast cancer, has gradually attracted people’s attention to the false-negative rate and postoperative complications. The aim of the study is to investigate the clinical value of preoperative contrast-enhanced ultrasound (CEUS) for intraoperative SLNB in early breast cancer patients. Methods: A total of 201 patients scheduled for SLNB from September 2018 to April 2021 were collected consecutively. Preoperative CEUS was used to identify sentinel lymph nodes (SLN) and lymphatic drainage in breast cancer patients. Results: The SLN identification rate of CEUS was 93.0% (187/201) and four lymphatic drainage patterns were found: single LC to single SLN (70.0%), multiple LCs to single SLN (8.0%), single LC to multiple SLNs (10.2%), and multiple LCs to multiple SLNs (11.8%). The Sen, Spe, PPV, NPV, AUC of CEUS, US and CEUS + US in diagnosis of SLNs were 82.7%, 80.4%, 73.8%, 87.4%, 0.815; 70.7%, 77.7%, 68.0%, 79.8%, 0.742; and 86.7%, 77.7%, 72.2%, 89.7%, 0.822, respectively. There was no statistically significant difference between the diagnostic performance of CEUS and CEUS + US (p = 0.630). Conclusions: CEUS can be used to preoperatively assess the lymphatic drainage patterns and the status of the SLNs in early breast cancer to assist precision intraoperative SLNB.

High-resolution three-dimensional imaging for precise staging in melanoma

IntroductionMany cancer guidelines include sentinel lymph node (SLN) staging to identify microscopic metastatic disease. Current SLN analysis of melanoma patients is effective but has the substantial drawback that only a small representative portion of the node is sampled, whereas most of the tissue is discarded. This might explain the high clinical false-negative rate of current SLN diagnosis in melanoma. Furthermore, the quantitative assessment of metastatic load and microanatomical localisation might yield prognosis with higher precision. Thus, methods to analyse entire SLNs with cellular resolution apart from tedious sequential physical sectioning are required. Patients and methodsEleven melanoma patients eligible to undergo SLN biopsy were included in this prospective study. SLNs were fixed, optically cleared, whole-mount stained and imaged using light sheet fluorescence microscopy (LSFM). Subsequently, compatible and unbiased gold standard histopathological assessment allowed regular patient staging. This enabled intrasample comparison of LSFM and histological findings. In addition, the development of an algorithm, RAYhance, enabled easy-to-handle display of LSFM data in a browsable histologic slide-like fashion. ResultsWe comprehensively quantify total tumour volume while simultaneously visualising cellular and anatomical hallmarks of the associated SLN architecture. In a first-in-human study of 21 SLN of melanoma patients, LSFM not only confirmed all metastases identified by routine histopathological assessment but also additionally revealed metastases not detected by routine histology alone. This already led to additional therapeutic options for one patient. ConclusionOur three-dimensional digital pathology approach can increase sensitivity and accuracy of SLN metastasis detection and potentially alleviate the need for conventional histopathological assessment in the future. German clinical trials register(DRKS00015737).

Diagnostic efficacy of sentinel lymph node in breast cancer under percutaneous contrast-enhanced ultrasound: An updated meta-analysis.

BackgroundTo investigate the diagnostic efficacy of sentinel lymph nodes (SLN) in breast cancer by percutaneous contrast‐enhanced ultrasound (CEUS) through pooled analysis of relevant studies published before June 2021.MethodsWe conducted a systematic review and meta‐analysis of relevant studies by searching the electronic databases of PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang and VIP and the studies were screened according to their inclusion and exclusion criteria. Sensitivity (SEN), specificity (SPE), positive likelihood ratio (+LR), negative likelihood ratio (−LR) and diagnostic odds ratio (DOR) were calculated by Meta‐disc 1.4 software and the summary receiver operating characteristic (SROC) curve and area under the curve of ROC (AUC) were constructed.ResultsTwenty‐two publications evaluating the diagnostic efficacy of SLN in breast cancer under percutaneous CEUS were included in the meta‐analysis. The diagnostic sensitivity, specificity were 0.86 (95% CI: 0.83–0.88) and 0.89 (95% CI: 0.87–0.91) for SLN in breast cancer detected by percutaneous CEUS respectively using a random effect model. The +LR and –LR were combined in a random effect model due to significant statistical heterogeneity (p < 0.05). The pooled +LR, −LR were 7.06 (95% CI: 4.34–11.50), and 0.17 (95% CI: 0.12–0.24), respectively. The combined DOR was 53.32 (95% CI: 29.74–95.61) for SLN diagnosis in breast cancer by percutaneous CEUS under a random effect model. The AUC was 0.94 which indicated that CEUS had high diagnostic efficacy of SLN in patients with breast cancer.ConclusionsCEUS is a noninvasive method for the detection SLN in patients of breast cancer with relative high prediction efficacy.

Axillary management based on American college of surgeons oncology group Z0011 criteria makes it possible to omit intraoperative diagnosis of sentinel lymph nodes in early breast cancer patients.

The ACOSOG Z0011 trial has resulted in the omission of axillary lymph node dissection (ALND) in early breast cancer patients with one or two metastatic sentinel lymph nodes (SLNs). There has been increasing interest in the necessity of intraoperative assessment of SLNs in patients treated based on the Z0011 criteria. We evaluated the utility of intraoperative assessment in these eligible patients. A total of 1396 patients were treated following the Z0011 criteria from April 2012 to December 2019. We examined the proportion and clinicopathological features of patients who underwent ALND due to three or more metastatic SLNs and the sensitivity of intraoperative assessment. Only 16 (1.1%) patients had three or more metastatic SLNs diagnosed by intraoperative assessment, and they immediately underwent ALND. Of the clinicopathological factors, high clinical tumor stage (p=0.002) and high Ki-67 labeling index value (p=0.056) were more likely to be associated with the presence of three or more metastatic SLNs. The major independent risk factor for three or more metastatic SLNs was high clinical tumor stage (OR 3.94 [95% CI 1.42-11.0]; p=0.009). Intraoperative assessment had low sensitivity (70.5%) and a high false-negative rate (29.5%) in detecting SLN metastases. The main finding of our study was the small proportion of patients who required ALND due to three or more metastatic SLNs according to the Z0011 criteria. The Z0011 strategy enables intraoperative assessment of SLNs to be omitted in early breast cancer patients.

Near-infrared sentinel diagnostics in head and neck squamous cell carcinoma: a systematic review

Near-infrared fluorescence (NIR) imaging is a new technique for intraoperative identification of sentinel lymph nodes (SLN). It has shown promising results in several surgical specialties. This article reviews the current study situation of NIR SLN diagnosis of head and neck malignancy. Systematic literature search in the following online databases: PubMed, MEDLINE, Thompson Reuters Web of Science, SPIE for the search terms: sentinel node, sentinel node biopsy, head and neck squamous cell carcinoma, near-infrared imaging, indocyanine green, icg. Evaluation of scientific relevance of papers according to established criteria. Studies were analyzed in terms of clinical application, clinical reporting, identification rate, and false-negative rate. The identification rate of SLN is 97-100 %, with an average of 1.2-3.4 fluorescence positive lymph nodes per examination. The overall false-negative rate varies between 0 and 20 %. In the synopsis of the currently published results, NIR imaging promises the great potential to improve the diagnosis of SLN in carcinomas of the oral cavity and pharynx. A simple and fast procedure with high spatial resolution and without radiation exposure is beneficial.

Abstract PS1-04: Utility of rapid- immunohistochemistry using an alternating current electric field for intraoperative diagnosis of sentinel lymph nodes in breast cancer

Abstract Axillary lymph node status and pathological diagnosis of sentinel lymph nodes (SLNs) is an important factor that influences management of postoperative therapy. Recent reports indicate that one-step nucleic acid amplification (OSNA) and hematoxylin and eosin (HE)-stained frozen sections are effective for intraoperative diagnosis of SLNs. In the present study, we report a rapid-immunohistochemical staining (R-IHC) method that enables intraoperative detection of SLN metastases within 16 min using an anti-cytokeratin antibody. With this R-IHC system, we apply a high-voltage, low-frequency AC electric field to lymph node sections while they are incubating with the antibodies. The antibodies are mixed within microdroplets and the opportunity for contact between the antibody and antigen is increased. This greatly reduces the time required for the antigen-antibody reaction. This is the report on SLN diagnosis using R-IHC in patients with breast cancer. We prospectively examined 632 dissected SLNs from 260 breast cancer patients who underwent surgery at our institute between July 2014 and March 2020. The dissected SLNs were sectioned and conventionally stained with HE or immunohistochemically labeled with anti-cytokeratin antibody using R-IHC procedures. Intraoperative R-IHC analyses were completed within 16 min, after which diagnoses were made by two pathologists. The total time required for intraoperative diagnosis was about 20 min. In this study, R-IHC detected four metastatic SLNs that were undetected using conventional HE staining (10/52, 19.2%). Compared with subsequent permanent diagnosis, R-IHC offered 98.0% sensitivity, 100% specificity and 99.8% accuracy while those values for intraoperative HE were 80.4%, 100%, 98.4%, respectively (isolated tumor cells were counted as negative). These findings indicate R-IHC is a clinically applicable technique that enables precise, and quick intraoperative detection of micro- and macrometastases in breast cancer. Moreover, R-IHC is cost-effective method: it’s cost is less than a quarter of OSNA and previous report showed that the concentration of primary antibody could be reduced by more than 90% by using R-IHC because AC mixing activated antigen-antibody reaction. Another benefit is its ability to shorten the time needed for microscopic diagnosis itself. When using R-IHC, pathologists are able to readily find metastatic lesions, even within low-power fields (e.g. 40x). This reduces not only the time needed for intraoperative diagnosis, but also the effort necessary to find unclear lesions like small cancer cells (even though it is macrometastasis), micrometastasis, and artifacts of frozen section. This study was conducted at a single institute. Further investigation in a multi-institutional collaborative prospective study will be needed to confirm the utility of this method. But for now, R-IHC appears to be a cost-effective and clinically applicable method for diagnosis of breast cancer and SLN metastasis. Citation Format: Kaori Terata, Hiroshi Nanjo, Eriko Takahashi, Ryuta Nakamura, Yoichi Akagami, Ayuko Yamaguchi, Misako Yatsuyanagi, Chiaki Kudo, Yoshihiro Minamiya. Utility of rapid- immunohistochemistry using an alternating current electric field for intraoperative diagnosis of sentinel lymph nodes in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-04.

Discovery of novel phenaleno isoquinolinium-based fluorescence imaging agents for sentinel lymph node mapping.

Fluorescence imaging agents have recently received huge attention due to their important role in disease diagnostics. However, the intrinsic problems of these probes, such as complex synthetic routes and high molecular weight, remain challenging. Here, we developed novel phenaleno isoquinolinium-based fluorescent agents, Medical Fluorophores 37-41 (MF37-41), applicable to the quantitative and sensitive detection of sentinel lymph nodes (SLNs). These imaging agents showed no adverse effects on the proliferation of immune and normal cells and did not induce in vivo toxicity. In vivo fluorescence lifetime imaging demonstrated the accumulation of phenaleno isoquinolinium salts in the SLNs of nude mice within 15 min postinjection, consistent with our biodistribution findings. These results suggest that phenaleno isoquinolinium salts are feasible fluorescence imaging agents that can be used as potential lymphatic tracers.

Intra-operative molecular diagnosis of sentinel lymph node and prediction of non-sentinel lymph node metastasis in breast cancer patients.

Intra-operative molecular diagnosis of sentinel lymph node and prediction of non-sentinel lymph node metastasis in breast cancer patients.

Identification of sentinel lymph nodes using contrast-enhanced ultrasound in breast cancer patients who underwent neoadjuvant chemotherapy.

59 Background: The aim of this prospective study was to evaluate the feasibility of contrast-enhanced ultrasonography (CEUS) for the identification of sentinel lymph node (SLN) in breast cancer patients with cN0 following neoadjuvant chemotherapy (NAC). Methods: Patients with cN0 following NAC (n=66) received a periareolar injection of SonoVue followed by ultrasound (US) to identify contrast-enhanced SLN before surgery. All patients underwent axillary lymph node dissection for verification of axillary node status after the SLN biopsy. The identification rate, sensitivity, specificity, accuracy, false negative rate, negative predictive value, positive predictive value was recorded. Results: In almost all cases, the SLNs were easily identified with an identification rate of 98.5 % (65/66). Compared with pathological diagnosis, sensitivity, specificity, accuracy, and false negative rate of CEUS for SLN diagnosis were 66.7%, 95.8%, 78.8%, and 14.3% respectively. Conclusions: Identification of SLN by CEUS is a technically feasible method with an identification rate as high as 98.5%. [Table: see text][Table: see text]