Blue Nodes Research Articles

Exploring methylene blue as an effective alternative to radiotracer for sentinel lymph node biopsy in early breast cancer in resource-limited settings

Background: Sentinel lymph node biopsy is the recommended approach in the evaluation of axilla during breast cancer surgery. This study evaluated the results of patients who underwent methylene blue sentinel lymph node biopsy. Methods: The study included 35 female patients with T1, T2 and T3 tumours. 5 ml of 1% methylene blue was injected into the periareolar region. The axillary sentinel lymph node was found and removed, and axillary dissection was performed. The sentinel lymph node and axillary dissection specimen were histopathologically examined, and the results were compared. Results: The sentinel lymph node was found in 33 (90%) patients. There were no complications associated with the use of methylene blue dye. Methylene blue-stained sentinel nodes were histologically negative for malignancy in 42% and positive in 58% of patients. Corresponding to sentinel nodes, the final axillary staging was negative in 60% and positive in 40% of patients. On diagnostic accuracy parameters, the sensitivity of the methylene blue method in early breast cancer (cT1-3N0M0) patients was 90.47%, and the specificity was 100%. The PPV of the technique under study was found to be 100% and NPV was 85.71%. The accuracy rate was 93%, and the false negative rate was identified as 9.5%. Conclusions: Sentinel lymph node biopsy by methylene blue is a method that can be applied with high accuracy. Methylene blue can be considered as an alternative to radio colloid dye in sentinel lymph node biopsy in a limited resource setting.

Intraoperative Nodal Palpation is a Mandatory Component of Sentinel Lymph Node Biopsy for Breast Cancer

Background: In the era of Z-0011, it is mandatory to decrease not only the false negative rate (FNR) of sentinel lymph node (SLN) biopsy but also the risk of residual metastatic nodes after SLN biopsy. Method: SLN biopsy with intraoperative nodal palpation (INP) was performed in patients with clinically node-negative (cN0) breast cancer. All identified blue and hot nodes were removed as blue/hot SLNs, and any suspicious palpable nodes were removed as palpable SLNs. Nodes that were incidentally removed with neighboring the blue/hot SLNs were classified as para-SLNs. Patients with positive SLNs on frozen section underwent axillary lymph node dissection (ALND) except for patients who met the Z-0011 and AMAROS criteria for exemption. Results: Palpable SLNs and para-SLNs were identified in 202 patients. Of 200 patients, excluding 2 patients only with palpable SLNs, 46 patients had involvements of blue/hot SLNs, and 14 had palpable and para-SLNs harboring additional metastasis. When false negative rate (FNR) was calculated based on blue/hot SLNs and palpable SLNs, the additional use of INP resulted in a FNR of 45.2%. Subsequently, ALND was performed in 43 patients with positive blue/hot or palpable SLNs. Residual nodal involvement was found in 28 (65%) of 43 patients after removing blue/hot SLNs. However, after removing palpable SLNs, the rate of residual nodal metastases significantly decreased from 65% (28/43) to 36% (13/36) (p=0.0133). Conclusion: INP decreased both the FNR of SLN biopsy and the risk of residual metastatic nodes after SLN biopsy.

Clinical utility of artificial intelligence–augmented endobronchial ultrasound elastography in lymph node staging for lung cancer

ObjectiveEndobronchial ultrasound elastography produces a color map of mediastinal lymph nodes, with the color blue (level 60) indicating stiffness. Our pilot study demonstrated that predominantly blue lymph nodes, with a stiffness area ratio greater than 0.496, are likely malignant. This large-scale study aims to validate this stiffness area ratio compared with pathology. MethodsThis is a single-center prospective clinical trial where B-mode ultrasound and endobronchial ultrasound elastography lymph node images were collected from patients undergoing endobronchial ultrasound transbronchial needle aspiration for suspected or diagnosed non–small cell lung cancer. Images were fed to a trained deep neural network algorithm (NeuralSeg), which segmented the lymph nodes, identified the percent of lymph node area above the color blue threshold of level 60, and assigned a malignant label to lymph nodes with a stiffness area ratio above 0.496. Diagnostic statistics and receiver operating characteristic analyses were conducted. NeuralSeg predictions were compared with pathology. ResultsB-mode ultrasound and endobronchial ultrasound elastography lymph node images (n = 210) were collected from 124 enrolled patients. Only lymph nodes with conclusive pathology results (n = 187) were analyzed. NeuralSeg was able to predict 98 of 143 true negatives and 34 of 44 true positives, resulting in an overall accuracy of 70.59% (95% CI, 63.50-77.01), sensitivity of 43.04% (95% CI, 31.94-54.67), specificity of 90.74% (95% CI, 83.63-95.47), positive predictive value of 77.27% (95% CI, 64.13-86.60), negative predictive value of 68.53% (95% CI, 64.05-72.70), and area under the curve of 0.820 (95% CI, 0.758-0.883). ConclusionsNeuralSeg was able to predict nodal malignancy based on endobronchial ultrasound elastography lymph node images with high area under the receiver operating characteristic curve and specificity. This technology should be refined further by testing its validity and applicability through a larger dataset in a multicenter trial.

Majority opinion diffusion: when tie-breaking rule matters

Consider a graph G, which represents a social network, and assume that initially each node is either blue or white (corresponding to its opinion on a certain topic). In each round, all nodes simultaneously update their color to the most frequent color in their neighborhood. This is called the Majority Model (MM) if a node keeps its color in case of a tie and the Random Majority Model (RMM) if it chooses blue with probability 1/2 and white otherwise. We study the convergence properties of the above models, including stabilization time, periodicity, and the number of stable configurations. In particular, we prove that the stabilization time in RMM can be exponential in the size of the graph, which is in contrast with the previously known polynomial bound on the stabilization time of MM. We provide some bounds on the minimum size of a winning set, which is a set of nodes whose agreement on a color in the initial coloring enforces the process to end in a coloring where all nodes share that color. Furthermore, we calculate the expected final number of blue nodes for a random initial coloring, where each node is colored blue independently with some fixed probability, on cycle graphs. Finally, we conduct some experiments which complement our theoretical findings and also let us investigate other aspects of the models.

Energy capable protocol for heterogeneous blue brain network

The Blue Brain has a wide range of applications, which raises a number of challenging issues. Electronics may continuously monitor their surroundings depending on the real data that their Blue Brain nodes are acquiring by employing situational intelligence based on the Blue Brain environment. The Blue Brain does more than only monitor user behavior when utilizing this technology. Blue Brain is linked to a critical prerequisite for energy-efficient communication methodologies. Through the Blue Brain network, it utilizes the heterogeneity and variety of the interconnected components. Blue Brain nodes that are outsourced and have limited energy resources must utilize less energy. IoT nodes with differing energy levels are frequently dispersed across different geographic regions. The main goal of this work is to provide an energy-efficient Blue Brain framework capable of managing cluster head (CH) selection and Blue Brain node clustering. The appropriate CHs are selected, and an energetic cutoff concept is developed to guarantee that energy is shared equally among the CHs and participating Blue Brain nodes. The proposed concept envisions three different kinds of Blue Brain nodes for a Blue Brain infrastructure: expert, intermediary, and normal Blue Brain nodes. Level 1 Blue Brain nodes are regarded as normal nodes; level 2 nodes are regarded as intermediate Blue Brain nodes; and level 3 nodes are regarded as expert Blue Brain nodes. Level 1 Blue Brain nodes use the least amount of energy. The outcomes of the simulation demonstrate that the recommended strategy outperforms other existing methods.

Changes in the attraction area and network structure of recreation flows in urban green, blue and grey spaces under the impact of the COVID-19 pandemic

Despite increasing attention to the impact of the COVID-19 pandemic on outdoor recreation, there is limited knowledge about its effects on visitor travel across cities for recreation and changes in the recreation response of blue, green and grey spaces within cities. This study examines changes in the attraction area of inter-city recreation flows within Wuhan, China, before and after the COVID-19 pandemic. The results showed a significant decrease in average attraction distance from 861.74 km to 787.77 km after the pandemic, while attraction directions remained stable. Intra-city recreation routes tend to be simplified, with average length decreasing from 40.86 km to 30.52 km and node number of recreation routes reducing from 7.02 to 5.00. However, the proportion of blue nodes in recreation routes increased significantly from 17.45 % to 23.25 %, while the proportion of grey nodes decreased noticeably from 57.36 % to 52.75 %. The proportion of green nodes did not show a significant change, but when the number of nodes exceeded 6.18, the proportion of green nodes slightly decreased below pre-pandemic levels. With the increase in the length of recreation routes, the proportion of grey nodes gradually converged to around 42 % from around 54 % before the pandemic. The total proportion of agglomeration and diffusion nodes increased from 13.71 % to 20.01 %, while the balanced nodes decreased from 8.87 % to 6.93 % after the pandemic. Notably, 35.71 % of the functional nodes before the pandemic remained their original functional type after the pandemic, but 7.14 % of functional nodes converted to weak function. These findings can assist tourism departments and scenic spot managers in developing strategies that balance pandemic control and recreation needs.

Energy Proficient Secure Clustered Protocol in Mobile Wireless Sensor Network Utilizing Blue Brain Technology

Mobile Wireless Sensor Network (MWSN) guarantees copious applications in daily life of ordinary people, government bodies, commerce, defense and culture etc. Association along with the devices in blue brain to fetch diverse appliances in the real world is an exigent assignment. Several existed protocols proficiently indulgence both homogenous and heterogeneous devices. This research work conquers the gap between the physical wireless blue brain network surroundings and the factual heterogeneous network. This research work intention not only provide a proficient energy responsive clustering broadcasting protocol for blue brain network, excluding a real blue brain network design for probing the proposed protocol contrasted to existed tactics. Proficient cluster-head election amplifies the deployment of the blue brain nodes energy stuffing and therefore amplifies the network life-span and the packets relaying rate to the base station. Energy Proficient Secure Clustered (EPSC) exploits special weighted selection possibilities for electing a Cluster-head based on regions heterogeneity intensity. NS2 simulation demonstrates prolongs the network life-span, diminishes reclustering, enhanced security and amplifies throughput contrasted with BM-BWO. The results will be beneficial for the design process in WSN for blue brain application.

Methylene blue sentinel lymph node biopsy for breast cancer learning curve in the COVID-19 era: How many cases are enough?

Background: Sentinel lymph node biopsy (SLNB) is now the gold standard for early breast cancer with clinically negative lymph nodes (N0). According to the Indonesian Board-Certified oncologist surgeon, the learning curve for evaluating fellow breast surgeons to achieve this competency could have been shorter due to the COVID-19 pandemic. This study aims to see if the learning curve for sentinel lymph node (SLN) identification can be shortened. Methods: Trainee breast surgeons were taught to perform SLNB on breast cancer patients. Intraoperative assessment and completion of axillary lymph node dissection (ALND) were performed in the first setting for standardization with the attending surgeon. Sentinel lymph node identification was plotted on cumulative sum chart (CUSUM) limitations for evaluating the variability competency between the attending and trainee surgeons based on a target identification rate of 85%. Results: We concluded that CUSUM charts are the best tools currently available for assessing psychomotor learning SLNB. According to a CUSUM chart based on a reasonable set of parameters, the learning curve for SLNB using methylene blue dye is reached after 4-5 consecutive positively detected SLN. Conclusion: CUSUM Chart showed that experienced breast surgeons have completed the SLNB learning curve after 4-5 successful methylene blue attempts. In the future, this learning curve analysis can be applied to trainee breast surgeons by utilizing a proxy measure for failure, such as failure to identify the SLN.

Hot dots – which nodes should be removed in sentinel lymph node biopsy for melanoma?

Background Sentinel lymph node biopsy (SLNB) is a critical staging tool for melanoma patients. The optimal number of lymph nodes removed in SLNB remains unclear. In this study, we retrospectively analysed and tested different criteria for selecting sentinel lymph nodes (SLNs) by radiotracer uptake and blue dye, and their impact on nodal staging. We also evaluated the association between SLN tumour burden and radiotracer uptake. Methods The study population consisted of melanoma patients undergoing SLNB. During the operation all radioactive and blue nodes were removed and sent for histopathological analysis. The ex vivo radioactive count and presence of blue dye of each node were recorded, and these were correlated with presence and size of metastasis in each SLN. Results Altogether 175 patients with clinically occult metastasis presented with one or more positive, i.e. metastatic, SLNs. The mean number of lymph nodes removed was 4.5, and the mean number of positive lymph nodes was 1.5 per patient. The most radioactive or hottest node was negative in 38 patients (22%). By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients would have been staged correctly. In five patients, metastasis was found solely in a SLN with radioactivity <10% of the hottest node. Of all 267 positive nodes removed, 125 (47%) contained blue dye. Patients with a negative hottest node were associated with lower SLN tumour burden. Conclusions By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients with SLN metastases are correctly staged with or without using blue dye.

THE COMPARISON OF RADIOCOLLOID, BLUE DYE AND A COMBINED METHOD FOR SENTINEL LYMPH NODE BIOPSY IN EARLY-STAGE BREAST CANCER

This study aims to compare the performance of radiocolloid, blue dye and a combined method for sentinel lymph node biopsy in early breast carcinoma. One hundred seventy-two clinically node-negative, early-stage breast cancer patients who underwent combined method sentinel lymph node biopsy (SLNB) with 99mTc-nanocolloid and blue dye were recruited. The peri-areolar injection is the method used in both techniques. The hot node contained only radiocolloid, the blue node contained only blue dye, and the hot-blue node contained both tracers. The detection, metastatic, and failure rate of the combined, radiocolloid, and blue dye methods were determined by analysing the number of hot and blue nodes in all patients, all excised nodes, and metastatic nodes. The association between clinicopathological factors and the detection of sentinel lymph nodes (SLN) was analysed. The overall SLN detection rate was 98.2% (169/172) for radiocolloid, 95.9% (165/172) for blue dye, and 99.4% (171/172) for the combined method. The metastatic rate was 19.2% (33/172). Among the 33 metastatic-node cases, the combined, radiocolloid and blue dye method failed to identify 1, 1 and 4 cases, respectively. Therefore, the failure rate of the combined, radiocolloid, and blue dye method was 3.0% (1/33), 3.0% (1/33) and 12.1% (4/33), respectively. No significant association between clinicopathological factors and SLN detection was observed. The combined method of SLNB yielded the highest detection rate when compared to the radiocolloid-alone and blue-dye-alone methods. The radiocolloid method detected more SLN than the blue dye method. Therefore, incorporating the radiocolloid method in the blue dye method will improve the SLN identification rate and reduce the failure rate of metastatic detection.

Abstract P2-14-10: Axillary Reverse Mapping Aids in Reducing the Rates of BCRL in Underserved Ethnically Diverse Population

Abstract Background: Breast Cancer Related Lymphedema (BCRL), is a long-term side effect affecting the patient’s quality of life after lymph node surgery. Historically BCRL is seen in 5-7% and 15-40% of patients undergoing sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) respectively; with the risk increasing two-fold in low-income and ethnic minority groups. Axillary Reverse Mapping (ARM) is a novel technique to distinguish drainage pathways of the arm and breast, and prior studies have reported significantly lower rates of BCRL with ARM. Lymphatic re-approximation can prevent and/or reduce lymphedema rates in cases where crossover nodes are encountered. Furthermore, blue nodes can be preserved during ALND; however, if resected during ALND, lymphatic venous (LYMPHA) procedure can help to restore lymphatic flow. However, there is a paucity of literature looking at the utility of ARM in ethnically minority groups. Therefore, we aimed to evaluate the prevalence of lymphedema in our patient population with breast cancer undergoing SLNB and ALND using ARM and in turn compare these findings to historical controls. Materials &amp; Methods: A retrospective study was carried out on patients who underwent axillary surgery with ARM from January 2019 to July 2021. Patient demographics such as age, BMI, gender, and ethnicity were recorded. Patients undergoing mastectomy vs breast conservation with SLNB ± ALND associated with ARM were monitored for lymphedema for a year at 3-month intervals using SOZO® scores, and then for another 2 years clinically. At each follow-up, SOZO® scores were computed using bioimpedance spectroscopy and compared to preoperative baseline scores. Results: A total of 142 patients’ data was evaluated, of which 83.8% belonged to the minority group (African American = 46, Hispanic = 63, Asian = 10). Mean BMI accounted for 29.1+5.31. Breast conservation surgery and mastectomy were performed in 71.8% (n=102) and 28.1% (n=40) of patients respectively. SLNB was performed on 88.7% (n=126) of the patients and ALND was carried out on 11.3% (n=16). Furthermore, 73.9% (n=105) of the patients underwent radiation therapy. Positive lymph nodes were identified in 24.6% (n=35) of patients. Blue nodes and blue lymphatics were encountered in 17.6% (n=25) and 32.4% (n=46) of patients respectively. Out of the blue nodes identified (n=25), 44% (n=11) were excised and 32% (n=8) were diagnosed as crossover nodes. All the crossover nodes were resected but none of them contributed to the development of lymphedema. Moreover, 90.9% of the patients with blue lymphatics underwent lymphatic re-approximation after excision of the blue nodes. Of the 142 patients, 59 had a three-month follow-up of which 2 patients (3.4%) developed clinical lymphedema diagnosed via SOZO® who had undergone SLNB which resolved by 6-month follow-up. Additionally, compared to the historical incidence of BCRL which accounts for up to 40.4% in ethnic minorities, we found a significantly lower incidence of lymphedema (p&amp;lt; 0.001) in our patient population. Moreover, in our study, ALND and radiation therapy did not contribute to lymphedema rates. Conclusion: ARM procedure can significantly lower BCRL even in ethnically minority groups. 3.4% of patients undergoing SLNB developed BCRL, which was significantly lower than historically reported data. Furthermore, in our study, no patients who underwent ALND developed lymphedema. Also, crossover nodes or radiation therapy did not contribute to the development of lymphedema after surgery demonstrating the effectiveness of ARM technique. Further studies with larger sample size and longer follow-up duration are necessary to better understand the utility of ARM technique in this population. Table 1 Baseline characteristics and follow-up data of the patients undergoing Axillary Reverse Mapping with SLNB ± ALND Citation Format: Fardeen Bhimani, Maureen McEvoy, Kelly Johnson, Sheldon Feldman. Axillary Reverse Mapping Aids in Reducing the Rates of BCRL in Underserved Ethnically Diverse Population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-10.

Abstract OT2-07-01: Feasibility study to evaluate performance of the LUM Imaging System for intraoperative detection of residual tumor in breast cancer patients receiving and not receiving neoadjuvant therapy

Abstract Background: Microscopically tumor-free lumpectomy margins are critical for safe breast conserving surgery. With current tools, 15%-25% of lumpectomies have positive margins that require second surgical procedures and increase cost and patient discomfort. Additionally, current lumpectomy margin assessment techniques show poor performance in predicting residual disease at re-excision, with a PPV of 35%. Better detection tools are needed to identify residual cancer during the initial lumpectomy and reduce second operations. LUM015 is a protease-activated fluorescent imaging agent that accumulates in tumor cells and tumor associated macrophages after preoperative intravenous injection. The LUM Imaging System visualizes activated LUM015 in the lumpectomy cavity via a hand-held wide field detector and proprietary tumor detection software. This system has been tested in multiple single-site studies and two prospective multi-site studies enrolling &amp;gt;600 patients, and demonstrated successful detection of residual lumpectomy cavity tumor. Initial studies excluded the approximately 20% of patients receiving neoadjuvant therapy. Patchy tumor cell death with preoperative therapy can leave small, multifocal deposits of tumor invisible on pre-operative imaging and not palpable or visible during surgery. We now evaluate the LUM Imaging System in patients with and without neoadjuvant therapy. Trial Design and Specific Aims: This prospective, multi-center study at 6 US sites tests the LUM Imaging System in lumpectomy surgery after neoadjuvant therapy to evaluate potential impact of treatment-related tissue changes and tumor cell death on tumor detection algorithms. An initial cohort of 10 patients address the objective of algorithm development. A second cohort of 104 patients will further evaluate the feasibility of the LUM Imaging System after neoadjuvant therapy. A third cohort will enroll 208 patients who have not received neoadjuvant therapy. All cohorts are evaluated for safety and for reduction in residual tumor after LUM Imaging System guidance compared to standard of care lumpectomy. After excision of the main lumpectomy specimen, patients are randomized 3:1 to device or control arms. In the device arm, the cavity is imaged and margins with LUM015 signal are excised. Final comprehensive shaved margins are removed in both arms to evaluate extent of residual disease after the use of the LUM Imaging System or after standard lumpectomy. No LUM Imaging is performed in the control arm, however, all patients are injected with LUM015 to evaluate drug safety. Patient reported outcomes assessing re-excision concerns, breast appearance and preferences for treatment type are collected. Eligibility Criteria: This study seeks to enroll women 18 and older with histologically confirmed primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy who have received any form of neoadjuvant treatment prior to surgery (cohorts 1 and 2) or who have not received any therapy prior to lumpectomy (cohort 3). Patients allergic to polyethylene glycol or intravenous contrast agents are excluded. Use of blue node mapping dyes before imaging with the LUM015 is not allowed per study protocol. Accrual and Study Progress: Cohort 1 has completed enrollment and interim analysis. No new risks specific to the neoadjuvant population were identified. LUM015 fluorescent signals measured in neoadjuvant patients were within the expected range, and no changes to the tumor detection algorithm were required. Cohorts 2 and 3 have enrolled a total of 38 patients. This trial is registered as NCT04440982. The NIH funds this study through a R01 grant issued to Massachusetts General Hospital. Citation Format: Irene L. Wapnir, Kelly K. Hunt, E Shelley Hwang, Kate Smith, Peter Blumencranz, David Carr, Jorge Ferrer, Heidi Santa Cruz, Alexandra Webster, Julia Shanno, Alexander Pogrebinsky, Manna Chang, Barbara L. Smith. Feasibility study to evaluate performance of the LUM Imaging System for intraoperative detection of residual tumor in breast cancer patients receiving and not receiving neoadjuvant therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-07-01.

Abstract B042: Sentinel lymph node detection in breast cancer: Comparison of blue dye and filtered Technetium 99m sulphur colloid radiotracer injection

Abstract Aim: This prospective study was performed to compare the identification rate, sensitivity and specificity of blue dye and filtered Technetium 99m labelled sulphur colloid (Tc99m SC), individually and in combination for the detection of sentinel lymph nodes in clinically node negative early-stage breast cancer. Materials and methods: Thirty-two women with biopsy-proven breast cancer (cT1N0M0-T2N0M0) were included in this prospective study over a period of 18 months (2019-2020). Four peri-areolar intradermal injections of filtered Tc99m SC were administered 2-3 hours before surgery. Sequential dynamic anterior images of the chest were acquired on a gamma camera, followed by anterior and anterior oblique static images and hybrid single photon emission computed tomography / computed tomography (SPECT/CT) of the affected breast and ipsilateral axilla. Pre-operatively, the sites of detected sentinel lymph nodes (SLNs) were marked on the skin surface using a hand-held gamma probe. SLNs were then identified intra-operatively after peri-tumoral methylene blue injection (blue nodes) and with the gamma probe (hot nodes). These SLNs were removed and sent for frozen section histopathology separately, labelled as hot only, blue only and hot and blue. All patients underwent axillary lymph node dissection (ALND). The final histopathology of all lymph nodes excised during ALND and SLN biopsy were analysed. Identification rate, sensitivity and specificity of both the methods for SLN detection individually and in combination were compared. Results: SLN data of 32 female patients aged 54.7±10.6 years with cT1N0M0-T2N0M0 was analysed. In 87.5% of patients (n=28) the same lymph node was identified by blue dye and filtered Tc99m SC and discordance was seen in 12.5% (n=3) patients. No SLN was detected by any method in one patient. Identification rate of filtered Tc99m SC alone, blue dye alone and combination techniques was 96.9% (n=31), 93.8% (n=30) and 96.9% (n=31) respectively. Of total 593 dissected lymph nodes including 78 SLNs (average 2.4±1.7 per patient), metastasis was found in 198 lymph nodes (12/32 patients). The sensitivity and specificity of the procedure considering only filtered Tc99m SC, blue dye alone and combination of the two tracers was found to be 83.3% (95% CI of 51.6-97.9) and 100% (95% CI of 82.4-100), 75% (95% CI of 42.8- 94.5) and 100% (95% CI of 81.5 -100) and 83.3% (95% CI of 51.6-97.9) and 100% (95% CI of 82.4-100) respectively. Conclusion: SLNB with filtered Tc99m SC using the intra operative gamma probe has better identification rate and sensitivity than blue dye in detecting SLN, while preoperative SPECT/CT helped the surgeon to locate the SLN during surgery. Blue dye has a complementary role in identifying the SLN due to ease of visualisation while operating. Citation Format: Anish Bhattacharya, Yamini Mathur, Ishita Laroiya, Amanjeet Bal, Sarika Sharma, Bhagwant R. Mittal. Sentinel lymph node detection in breast cancer: Comparison of blue dye and filtered Technetium 99m sulphur colloid radiotracer injection [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B042.

Triple mapping for axillary staging after neoadjuvant therapy: Axillary reverse mapping with indocyanine green and dual agent sentinel lymph node biopsy

Axillary staging is 1 of the major issues of current breast cancer management after neoadjuvant systemic therapy (NST). Sentinel lymph node biopsy (SLNB) is an option for clinically node negative patients. Axillary reverse mapping (ARM) was introduced to identify and preserve the lymphatic drainage from the arm. The aim of the presented study is to employ triple mapping (radiocolloid, blue dye and indocyanine green [ICG]) to assess the crossover rate and metastatic involvement of ARM nodes after NST. Clinically node positive patients before NST who were converted to N0 and scheduled for targeted axillary dissection were included. sentinel lymph node (SLN) mapping was performed via dual agent mapping. ICG was used for ARM procedure. Blue, hot and fluorescent nodes and lymphatics were visualized in the axilla using infrared camera system and dual opto-nuclear probe (Euoroprobe3). Fifty-two patients underwent targeted axillary dissection and ARM procedures 12 out of whom had axillary node dissection. 45 of the 52 patients had at least 1 hot or blue SLN identified intraoperatively. Of these, 61.5% cases had hot SLNs, 42.3% had hot and blue, 15.4% had hot/blue/fluorescent, 7.7% had blue/fluorescent, 6 11.5% had hot/fluorescent and 7 13.5% had only clipped nodes. The overall identification rate of ARM-nodes by means of ICG technique was 86.5%. Overall crossover of ARM nodes with SLNs was determined in 36.5%. The ICG intensity was found to be higher in both hot and blue SLNS (8 out of 18 ICG positive cases, 44.4%). In 3 of 52 patients (5.7%) metastatic SLNs were hot or blue but fluorescent which predicts metastatic involvement of the ARM-nodes. More than 1-third of the patients revealed a crossover between arm and breast draining nodes. The higher observed rate of overlap might partially explain why more patients develop clinically significant lymphedema after NST even after sentinel lymph node biopsy alone. The triple mapping provides valuable data regarding the competency of lymphatic drainage and would have the potential to serve selecting patients for lymphovenous by-pass procedures at the index procedure. NST reduces the metastatic involvement of the ARM nodes. However, conservative axillary staging with sparing ARM nodes after NST necessitates further studies with larger sample size and longer follow-up.

Methylene blue sentinel lymph node biopsy for breast cancer learning curve in the COVID-19 era: How many cases are enough?

Background: Sentinel lymph node biopsy (SLNB) is now the gold standard procedure for early breast cancer with clinically negative lymph nodes (N0). According to the Indonesian Board-Certified oncologist surgeon, the learning curve for evaluating fellow breast surgeons to achieve this competency could have been shorter due to the COVID-19 pandemic. This study aims to see if the learning curve for sentinel lymph node (SLN) identification can be shortened and if imprint cytology (IC) can replace frozen sections (FS) for intraoperative analysis. Methods: Fellow breast surgeons were taught to perform SLNB on breast cancer patients. Intraoperative assessment and completion of axillary lymph node dissection (ALND) were performed in the first setting for standardization with the attending surgeon. Sentinel lymph node (SLN) identification was plotted on cumulative sum chart (CUSUM) limitations for evaluating the variability competency between attending surgeon and fellow surgeon based on a target identification rate of 85%. In addition, the accuracy of imprint cytology versus frozen section for identifying lymph node metastases was compared. Results: Consecutive 50 SLNBs were conducted during this period with attending and trainees split into two groups. After 13 consecutive tests, the CUSUM plot positively identified SLN as a significant achievement level of competency. Imprint cytology was shown to be inferior to frozen section cytology. The accuracy of imprint cytology is 91.8%, while the accuracy of frozen sections is 95.9%. Conclusion: According to a CUSUM chart based on a reasonable set of parameters, the learning curve for SLNB using methylene blue dye is reached after 13 consecutive positively detected SLN. Meanwhile, the frozen section is still the gold standard for determining the disorder of axillary lymph nodes, but the accuracy between the two methods can be comparable.

Integrating ecosystem services and landscape connectivity into the optimization of ecological security pattern: a case study of the Pearl River Delta, China.

The ecological security pattern (ESP) focuses on key ecological elements in ecosystems by identifying, combining, and evaluating these elements. This study attempts to identify the ESP of the Pearl River Delta (PRD) and provide suggestions for optimization. Ecosystem services were calculated and applied to construct the ecological resistance surface; morphological spatial pattern analysis (MSPA) and landscape connectivity analysis were used to identify ecological sources; and minimum cumulative resistance (MCR) model was applied to extract ecological corridors and ecological nodes. The results show that during 1995 to 2015, the main landscape transformation occurred between forest, cropland, and urban land, and the location of the transformation was mainly in the central part of the study area. Regarding the ESP, the average resistance value increased from 0.30 to 0.33; the area of ecological sources decreased by 5.12%; the ratio of total cumulative resistance to the length of the corridors increased by 14.82%; and the number of ecological nodes increased from 71 to 99. For the ESP optimization, based on the correction of the resistance surface, 1348km blue corridors and 61 blue nodes were extracted. Based on hot spot analysis, nine stepping stones were identified. This optimization compensates for the lack of ecological elements in the center of the study area, enhances weaker corridors, and improves the connectivity of the ESP, thus making the ESP more stable and complete. The ESP constructed and optimized in this paper holds great significance and serves as a valuable reference for ecological protection and environmental management.

111P Sentinel lymph node biopsy in post-neoadjuvant chemotherapy breast cancer patients using combination of fluorescein and blue dye versus blue dye alone: An interim analysis of a randomized controlled trial (SONAR-FB)

Sentinel lymph node biopsy (SLNB) is a standard procedure to determine the axillary lymph node(ALN) status in node-negative breast cancer(BC). Due to cost constraints and limited availability, the radiocolloid is being used in very few centers in developing countries. Fluorescein is inexpensive, sensitive fluorescent dye. SLNB in post neoadjuvant chemotherapy (NACT), has shown a higher false-negative rate (FNR) and lower identification rate(IR) comparing early BC. We studied the SLN IR and FNR of a dual tracer method, fluorescein plus methylene blue(FB) over methylene blue alone(B) in post NACT patients. It is a prospective, single-center, parallel-arm randomized controlled trial. All clinical node-negative, non-metastatic BC patients after NACT were included. They underwent axillary ultrasonography (AUS) to assess the morphologic appearance of the ALN to categorize it into normal or suspicious nodes. All patients were randomized before surgery. In one group, SLNB was done by FB and the other group by B alone after confirmation of non-allergy to the respective dye/dyes. All patients underwent ALN dissection. The primary objectives were SLN IR and FNR and the secondary objective was AUS's accuracy in the assessment of ALN pathological status. Out of 230 BC patients, 133 patients received NACT. Only 42 patients had clinically negative nodes after NACT. SLNB by FB and B was done in 21 patients and 20 patients, respectively. SLN could be identified in 20 out of 21 patients by the dual tracer(95%). Out of 20 patients, fluorescent nodes were identified in 19 (90.4%%) while blue nodes could be identified in 16 (76.1%). In the B group, Blue nodes were identified in 16/20 patients(80.0%).FNR with dual tracer was 11.1%(1/09 ) and FNR with blue dye was 16.6%( 1/06 ). AUS had 92% accuracy. A dual tracer. FB has a better IR and lowers FNR than B alone in post NACT breast cancer patients. It can be used as a low-cost and effective alternative to other dual tracers in low and middle-income countries.Moreover, excellent visualization of a lymphatic pathway by fluorescein can guide tracing the SLN.

Connecting the Dots: Fostering a Scholarly Community through Philanthropy&amp;Education

Connecting the Dots:Fostering A Scholarly Community Through Philanthropy & Education Noah D. Drezner With this issue of Philanthropy & Education, we celebrate five full years of the journal. In my editorial introducing the journal, I set the mission "to advance scholarship and inform practice around philanthropy broadly defined, including but not limited to, fundraising, volunteerism, civic engagement, alumni relations, corporate social responsibility, and prosocial behavior development" (Drezner, 2017, p. V). Further, I noted the need for the journal as there was evidence of a growing sub-field—often feeling disjointed across multiple disciplines—at the intersection of the scholarly study of philanthropy and education. My unstated hope for Philanthropy & Education was to help foster a scholarly community that could learn from one another, be in conversation with each other, and further the theoretical and practical implications of our sub-field through empirical research. Five years later, there is evidence that the journal is fulfilling its mission and that indeed there is a scholarly community of which we are all apart. The Association of College and Research Libraries (2015) define a community of scholars as "engag[ing] in sustained discourse with new insights and discoveries occurring over time as a result of varied perspectives and interpretations" (n.p.). This community of scholars can be seen in multiple ways. One such way is to look through a social network analysis of who is cited in the journal. In doing so, I am able to illustrate who our community is comprised of and how we are in conversation with one another. Scholars have long used social network analysis as an effective method for identifying the structure of intellectual or scholarly communities (Moody & Light, 2006; Pizmony-Levy, 2016; Wang, 2018). For exploring the social structure of publications in Philanthropy & Education, I assembled a small dataset with all publications in the journal and the citations included in them. I then coded the first author of each citation and standardized the names in terms of format. I focused on the first author for simplicity; future analysis should include all other authors. I used the clean dataset to construct a two-mode network with authors [End Page 1] (in rows) and publications in Philanthropy & Education (in columns). Each cell in the matrix was coded 1 if the author was cited in the publication, and 0 otherwise. From this network, I developed two simplified versions: (a) author co-citation network that shows for every two authors the extent to which they are cited together in multiple publications; (b) publication overlap network that shows for every two publications the extent to which they share authors (or cite the same authors). Over the first five volumes, including this issue, we have published 43 research articles and notes. Across this scholarship, 2,379 different articles, books, and other resources were cited. This includes 1,426 unique first authors. Of those, 71% were only cited in one of the 43 manuscripts, while 22% cited in two manuscripts, and 7% (100) cited three or more times. Figure 1 is a visualization of a two-mode social network exploring the 43 manuscripts (blue square nodes) and the 100 first authors that were cited by three or more manuscripts (red circle nodes). I excluded methodologists (e.g., Creswell; Merriam; and Yin) and organizations for the purposes of exploring the philanthropic studies network. The seven manuscripts that are isolated from the network (top left side) do not share first authors, cited at least three times, in common with any other manuscript in the network. As you can clearly see, the network includes one component with two clusters. The large cluster (center) is made up of articles that focused on higher education philanthropy; the smaller cluster (bottom left) focuses on k-12 education, and more specifically, philanthropic experiential learning. It is important to note that while these are two distinct clusters they do share some commonalties within the literature they cite. Taking a deeper dive into the connections across the manuscripts published over the last five years, figure 2 looks at articles (blue square nodes) that share at least six first authors in their references. In this analysis we had multiple components. For the purpose of this illustration...

Abstract OT2-12-02: Feasibility study to evaluate performance of the LUM imaging system for intraoperative detection of residual tumor in patients with breast cancer receiving neoadjuvant therapy

Abstract Background: Microscopically tumor-free lumpectomy margins are the goal for breast conserving surgery. With current tools, 15% to 25% of lumpectomies have positive margins and require a second surgical procedure increasing cost and patient discomfort. In addition, current lumpectomy margin assessment techniques show poor performance in predicting residual disease at re-excision, with a PPV of only 35%. Better detection tools are needed to guide the removal of cancer missed during the initial lumpectomy and reduce second operations. The LUM015 imaging agent is injected intravenously before surgery and its fluorescence signal is activated by proteases in tumor cells and the invasive front. The LUM Imaging System visualizes the activated LUM015 in the lumpectomy cavity via a hand-held detector and proprietary tumor detection software. This system was previously tested in multiple single-site studies and a prospective 234 patient multi-site study that demonstrated successful detection of residual cancer in the lumpectomy cavity. Initial studies excluded the ~20% of breast cancer patients receiving neoadjuvant therapy. Patchy tumor cell death with preoperative therapy can leave small, multifocal deposits of tumor invisible on pre-operative imaging and not palpable or visible during surgery. In this study, we are evaluating the LUM Imaging System in this patient population. Trial Design and Specific Aims: A prospective, multi-center study was designed to evaluate the potential impact of neoadjuvant therapy on tumor detection algorithms, which will be refined if needed. The first cohort of 10 patients will address this objective. A second cohort will further evaluate the feasibility, safety and efficacy of the LUM Imaging System in this patient population. 114 neoadjuvant therapy patients with invasive breast cancer and/or ductal carcinoma in situ will enroll at 6 US medical centers. After excision of the main lumpectomy specimen, patients are randomized 3:1 to device or control arms. In the device arm, the cavity is imaged and margins with LUM015 positive signal are excised. In the control arm, the surgeon records images within the cavity but no LUM015-directed margins are excised. Final comprehensive shave margins are removed in both arms to evaluate extent of residual disease after the use of the LUM Imaging System or after standard lumpectomy resection. Eligibility Criteria: This study seeks to enroll women, over the age of 18 and primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy who have received any form of neoadjuvant treatment prior to undergoing surgery. Exclusions include patients allergic to polyethylene glycol or contrast agents. Use of blue node mapping dyes before imaging with the LUM015 is not allowed. Accrual and Study Progress: Cohort 1 has completed enrollment and interim analysis. No new risks specific to this patient population were identified and the fluorescence signals measured were within the expected range resulting in no initial changes to the tumor detection algorithm. Four patients have enrolled into cohort 2. This trial is registered as NCT04440982. This study is funded by NIH grant R01CA212138 awarded to Dr. Barbara Smith. Citation Format: Kate P Smith, Jorge Ferrer, Alexandra Webster, Bridget Kelly, Brian Schlossberg, Manna Chang, Barbara Smith. Feasibility study to evaluate performance of the LUM imaging system for intraoperative detection of residual tumor in patients with breast cancer receiving neoadjuvant therapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-12-02.

Reverse Axillary Mapping in Breast Cancer using Double Dye: A Tertiary Cancer Center Experience

Background: Among the various methods in minimizing Limb Lymphoedema following ALND in Breast cancer, Axillary reverse mapping is a novel approach. Attempt to preserve the ARM node without threatening Oncological safety is a further step. Aim: To identify Blue ARM Node, intra operatively whether harbors metastases or not, defined by Radioactivity comparing with Histo pathological Examination. Materials and Method: The 30 cases of Breast cancer patients undergoing surgery along with Axillary dissection were considered for Double dye technique of ARM study with Radio colloid injection in subareolar region and 3ml of 5% methylene blue to the Arm,1 hour before starting surgery. At Axillary dissection, level I and level II nodal clearance done and the blue thin, tortuous lymphatics entering axilla are identified are followed medially, where blue nodes are usually identified below inferior to Axillary vein. The Blue nodes are considered belonging to upper limb called ARM node, whose radioactivity is recorded invivo, are dissected and sent for Histo pathological Examination. Results: The identification rate of blue lymphatics is about 77% (26 cases out of 30), the location of blue ARM node (70% identification rate, 21 out of 30 cases) were within 2cms inferior to Axillary vein lateral to Latissimus dorsi pedicle. The Radioactivity of the Blue ARM node more the 10% of the count at Subareolar region considered as Cross over Node (Blue+Hot) is observed among 2 patients, which confirmed with histopathologicaly positive for metastases, but rest of 19 (95.3%) Blue ARM node with less than 10% radioactivity (Blue +Cold), were Histopathologicaly Negative for metastases. Among 21 Blue ARM nodes, 2 nodes were metastatic amounting to 9.4% cases having cross over Lymphatics, identified by radioactivity. Conclusion: The Double dye Axillary Reverse Mapping study is a valuable armamentarium for the surgeons, during Breast Cancer surgery undergoing Axillary Lymphnode dissection to preserve uninvolved ARM Lymph node, thereby avoid Limb lymphedema without compromising Oncological safety.1