The FDA Sentinel Real World Evidence Data Enterprise (RWE-DE).

PURPOSE: The US Food and Drug Administration's Sentinel Innovation Center aimed to establish a query-ready, quality-checked distributed data network containing electronic health records (EHRs) linked with insurance claims data for at least 10 million individuals to expand the utility of real-world data for regulatory decision-making. METHODS: In this report, we describe the resulting network, the Real-World Evidence Data Enterprise (RWE-DE), including data from two commercial EHR-claims linked assets collectively termed the Commercial Network covering 21 million lives, and four academic partner institutions collectively termed the Development Network covering 4.5 million lives. RESULTS: We discuss provenance and completeness of the data converted in the Sentinel Common Data Model (SCDM), describe patient populations, and report on EHR-claims linkage characterization for all contributing data sources. Further, we introduce a standardized process to store free-text notes in the Development Network for efficient retrieval as needed. CONCLUSIONS: Finally, we outline typical use cases for the RWE-DE where it can broaden the reach of the types of questions that can be addressed by the Sentinel system.

Quantification of uncertainty in short-term tropospheric column density risks for a wide range of carbon monoxide.

The short-term risks associated with atmospheric trace gases, particularly carbon monoxide (CO), are critical for ecological security and human health. Traditional statistical methods, which still dominate the assessment of these risks, limit the potential for enhanced accuracy and reliability. This study evaluates the performance of traditional models (ARIMA), machine learning models (LightGBM, ConvLSTM2D), and optimized machine learning solutions (Bayes residual optimization ConvLSTM2D LightGBM, Bayes_CL) in predicting Sentinel 5P columnar CO levels. This study findings demonstrate that machine learning models and their optimized versions significantly outperform traditional ARIMA models in cross-validation (CV), visualization, and overall prediction performance. Notably, machine learning model based on Bayes and residual optimization (Bayes_CL) achieved the highest CV score (Bayes_CL R2 = 0.8, LightGBM R2 = 0.79, ConvLSTM2D R2 = 0.75, ARIMA R2 = 0.61), along with superior visualization and other metrics. Using Bayes_CL, we effectively quantified a 2.4% increase in columnar CO levels in mainland China in the second half of 2023, following the complete lifting of COVID-19 lockdowns. This study confirms that machine learning models can effectively replace traditional methods for short-term risk assessment of Sentinel 5P columnar CO. This transition holds significant implications for policy formulation, greenhouse effect assessment, and population health risk evaluation, especially in uncertain situations where human activities are severely disrupted, thereby affecting environmental safety.

Trends and efficacy of omitting axillary lymph node dissection in early-stage male breast cancer with limited nodal involvement: A population-based cohort study.

BACKGROUND: The effectiveness of sentinel lymph node biopsy (SLNB) versus axillary lymph node dissection (ALND) in managing early-stage male breast cancer (MBC) patients with T1-2 tumors and limited lymph node metastasis, all receiving radiotherapy, remains uncertain. This study examines trends and survival outcomes for SLNB and ALND in the United States. METHODS: We conducted a retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) data from 2010 to 2020 for MBC patients with T1-2 tumors and 1-2 positive lymph nodes undergoing radiotherapy. Patients were classified by nodes removed (SLNB ≤5, ALND ≥10), comparing overall survival (OS) and breast cancer-specific survival (BCSS) between the groups before and after propensity score matching. RESULTS: Of 299 MBC patients analyzed, SLNB usage increased from 18.8% in 2010 to 61.0% in 2020. Multivariable logistic regression highlighted significant associations of SLNB use with diagnosis year, race, surgery type, positive lymph node count, and metastasis size. No significant differences in 5-year OS (77.98% SLNB vs. 85.85% ALND, p = 0.337) or BCSS (91.54% SLNB vs. 94.97% ALND, p = 0.214) were observed. Propensity score matching (96 patients per group) confirmed similar 5-year OS (83.9% for SLNB vs. 82.0% for ALND, p = 0.925) and BCSS (90.1% for SLNB vs. 96.9% for ALND, p = 0.167). CONCLUSION: SLNB and ALND provide comparable survival outcomes in early-stage MBC patients with limited lymph node metastasis undergoing radiotherapy. The increased utilization of SLNB supports its consideration to reduce surgical morbidity in selected MBC patients despite limited direct evidence.

Agricultural pesticides in feathers of the burrowing owl (Athene cunicularia) and its relationship to land-use in the argentinean pampas.

The pampas of South America represent one of the most productive lands for agriculture in the world, and consequently this activity has expanded throughout the region, especially in Argentina. In this context, native fauna faces various risks associated with agriculture, with exposure to pesticides being one of the most dangerous and deadly. Assessing the impact of pesticides on wildlife becomes fundamental and the use of sentinel species emerges as an important tool to monitor environmental health. In this study, we determined pesticide levels in the burrowing owl Athene cunicularia nesting in both rural and urban areas of the argentinean pampas. We used a multiple scale approach to evaluate the influence of land-uses (urban, crops, and grazing fields) at the nesting site on the contaminant load of A. cunicularia individuals, and assessed the potential use of this owl as a sentinel species. From March 2018 to January 2020, A. cunicularia feathers were collected at their nest sites in one urban and two rural areas. These samples were analyzed for the presence of contaminants, including chlorpyrifos and 18 organochlorine pesticides. All the compounds analyzed were detected in A. cunicularia samples. The chlorpyrifos showed the highest frequency of occurrence and concentration, thus denoting the exposure of owls to current-use pesticides. ∑DDTs showed the highest occurrence among organochlorines, followed by ∑HCHs > ∑Endosulfans > ∑Heptachlors > ∑Drins = ∑Chlordanes > methoxychlor. Principal Component Analysis showed that most of the compounds found in A. cunicularia samples showed a positive association with grazing fields, suggesting that exposure to contaminants does not depend on specific habitat use at the local scale, but probably the regional scale. Our results evidenced the exposure of A. cunicularia individuals to past and current-use pesticides in the pampas of Argentina, and indicate that this owl would be useful as a sentinel species.

Difference between sentinel and non-sentinel lymph nodes in the distribution of dendritic cells and macrophages: An immunohistochemical and morphometric study using gastric regional nodes obtained in sentinel node navigation surgery for early gastric cancer.

The sentinel lymph node (SN) concept has a significant impact on cancer surgery. We aimed to examine which morphology of dendritic cells (DCs) and macrophages corresponds to "preconditioning" of the SN against cancer. Although macrophages are generally able to tolerate cancer metastasis, the CD169-positive subtype is believed to be a limited exception. Immunohistochemical and morphometric analyses were performed to examine DC-SIGN-, CD68-, and CD169-positive cells in SNs and non-SNs of 23 patients with gastric cancer with or without nodal metastasis. All patients survived for >5 years without recurrence. DCs were present in the subcapsular, paracortical, and medullary sinuses, the endothelia of which expressed DC-SIGN and smooth muscle actin (SMA). In the non-SNs of patients without metastasis, subcapsular DCs occupied a larger area than SNs, and this difference was statistically significant. Conversely, subcapsular DCs were likely to have migrated to the paracortical area of the SNs. DC clusters often overlapped with macrophage clusters; however, histiocytosis-like clusters of CD169-negative macrophages showed a smaller overlap. We found a significantly larger overlap between DC-SIGN and CD169-positive clusters in SNs than in non-SNs; the larger overlap seemed to correspond to a higher cross-presentation of cancer antigens between these cell populations. DC-SIGN-CD169-double positive cells might exist within this overlap. SNs in gastric cancers are usually preconditioned as a frontier of cancer immunity, but they may sometimes be suppressed earlier than non-SNs. DC-SIGN- and CD169-positive cells appeared to decrease owing to a long lag time from the primary lesion occurrence and a short distance from the metastasis.

Remote sensing detection of plastic-mulched farmland using a temporal approach in machine learning: case study in tomato crops.

The increasing use of plastics in rural environments has led to concerns about agricultural plastic waste (APW). However, the plasticulture information gap hinders waste management planning and may lead to plastic residue leakage into the environment with consequent microplastic formation. The location and estimated quantity of the APW are crucial for territorial planning and public policies regarding land use and waste management. Agri-plastic remote detection has attracted increased attention but requires a consensus approach, particularly for mapping plastic-mulched farmlands (PMFs) scattered across vast areas. This article tests whether a streamlined time-series approach minimizes PMF confusion with the background using less processing. Based on the literature, we performed a vast assessment of machine learning techniques and investigated the importance of features in mapping tomato PMF. We evaluated pixel-based and object-based classifications in harmonized Sentinel-2 level-2A images, added plastic indices, and compared six classifiers. The best result showed an overall accuracy of 99.7% through pixel-based using the multilayer perceptron (MLP) classifier. The 3-time series with a 30-day composite exhibited increased accuracy, a decrease in background confusion, and was a viable alternative for overcoming the impact of cloud cover on images at certain times of the year in our study area, which leads to a potentially reliable methodology for APW mapping for future studies. To our knowledge, the presented PMF map is the first for Latin America. This represents a first step toward promoting the circularity of all agricultural plastic in the region, minimizing the impacts of degradation on the environment.

Laparoscopic treatment of early-stage endometrial cancer: benefits of sentinel lymph node mapping and impact on lower extremity lymphedema.

OBJECTIVE: To evaluate the lymphatic-specific morbidity (specifically, lower extremity lymphedema) associated with laparoscopic management of early-stage endometrial cancer using the sentinel lymph node (SLN) algorithm by type of actual nodal assessment. METHODS: An ambispective study was conducted on consecutive patients surgically treated for apparent early-stage endometrial cancer who underwent laparoscopic staging according to the National Comprehensive Cancer Network SLN algorithm at a single institution from January 2020 to August 2023. Data on patient characteristics, surgical details, and post-operative complications were collected. Lymphedema screening was performed using a validated questionnaire. RESULTS: A total of 239 patients were analyzed, with a questionnaire response rate of 85.4%. The study population was grouped based on actual surgical staging: hysterectomy+SLN (54.8%), hysterectomy+systematic pelvic lymphadenectomy (27.2%), and hysterectomy only (18%). The prevalence of lymphedema was significantly lower in the hysterectomy+SLN group compared with the hysterectomy+systematic pelvic lymphadenectomy group (21.4% vs 44.6%, p=0.003). Multivariable analysis showed a threefold increase in the risk of lymphedema for the hysterectomy+systematic pelvic lymphadenectomy group compared with the hysterectomy+SLN group: OR 3.11 (95% CI 1.47 to 6.58). No significant associations were found between lymphedema and other patient or tumor characteristics. CONCLUSION: In the setting of a laparoscopic approach for early-stage endometrial cancer surgery, SLN mapping is associated with a significant reduction in lymphatic complications compared with a systematic lymph node dissection. Our findings provide additional evidence endorsing the adoption of SLN mapping during minimally invasive surgery for endometrial cancer. This technique ensures comparable diagnostic accuracy and also minimizes complications.

Nonsentinel lymph node metastases in cases of micrometastasis detected by sentinel lymph node biopsy after neoadjuvant chemotherapy.

BACKGROUND: There is a clinical need to omit axillary lymph node dissection (ALND) when residual disease in sentinel lymph nodes (SLNs) is low after neoadjuvant chemotherapy (NAC). This study aimed to clarify the relationship between micrometastasis in SLNs after NAC and additional non-SLN metastases by analyzing SLN biopsy results followed by ALND. METHODS: This retrospective study reviewed clinical records of patients who underwent breast cancer surgery between January 2010 and June 2022 after NAC at Samsung Medical Center. Of 3944 patients, 806 underwent SLN biopsy followed by ALND. Intraoperative frozen SLN biopsy results were examined, including the number and size of metastases in SLNs, and further investigated the number of additional non-SLN metastases. RESULTS: Among the 806 patients, 95 (11.8%) had micrometastasis on SLNs in frozen sections, of which 89 (93.7%) had clinically node-positive (cN1-3) breast cancer before NAC. Twenty-three patients (24.2%) exhibited positive additional non-SLNs after ALND. The presence of lymphovascular invasion (vs. absence; odds ratio [OR] = 4.02, p = .0151) and having two or more SLNs with micrometastasis (vs. a positive SLN; OR = 3.65, p = .0301) were significantly associated with additional non-SLN metastases. Tumor subtypes and breast pathological complete response after NAC showed no correlation with the additional non-SLN metastases. CONCLUSION: The study identified a 24.2% possibility of additional non-SLN metastasis if micrometastases was detected in the SLN after NAC. This rate is significant, indicating that ALND cannot be omitted if low volume residual disease, such as micrometastasis, is identified in the SLN after NAC.

Link between isolated para-aortic lymph node metastasis and intrauterine cancer site in early stage endometrial cancer.

OBJECTIVE: Missing occult para-aortic lymph node metastasis is one of the primary concerns of sentinel lymph node biopsy in endometrial cancer. Our study aimed to evaluate the relationship between intrauterine cancer site and isolated para-aortic lymph node metastasis to tailor treatment and reduce the false negative rate of the sentinel lymph node procedure. METHODS: A retrospective, multicenter, case control study was performed in four international centers. All patients with positive lymph nodes who had complete surgical staging with pelvic and para-aortic lymphadenectomy, between January 2013 and December 2023, were included. Detailed descriptions of the cancer location within the uterine cavity on the cranio-caudal plane and the myometrial wall involvement on the cranio-caudal and ventro-dorsal planes were collected, as were clinical data and cancer histological features. Patients with isolated para-aortic lymph node metastasis were allocated to group 1; patients with pelvic lymph node metastasis and those with both pelvic and para-aortic lymph node metastasis were allocated to group 2. The groups were compared according to the variables collected. RESULTS: 200 preoperative early stage endometrial cancer patients with postoperative International Federation of Gynecology and Obstetrics 2009/2023 stage IIIC1/IIIC2 were included in our study: 42 patients (21%) with isolated para-aortic lymph node metastasis were allocated to group 1 and the remaining patients to group 2. The two groups had comparable clinical and pathological characteristics (p>0.05): mean age was 66.5±10.3 (group 1) and 63.5±11.9 (group 2); endometrioid histotype was the predominant one for both groups (50%); most patients had myometrial infiltration >50% (80.9% and 79.7%), grade 3 (61.9% and 63.9%), and lymph vascular space invasion (78.5% and 82.2%). Cancers involving the fundal uterine cavity, the fundal myometrial wall, or the anterior myometrial wall were 3.11 (1.04-9.27), 3.03 (1.12-8.21), and 2.12 (0.77-5.80) times more likely to metastasize only to para-aortic lymph nodes compared with cancers located in other uterine sites. CONCLUSIONS: In this study, the intrauterine location of the cancer determined the site of lymph node metastasis. When the tumor involved the fundus (cavity or wall) and infiltrated exclusively the anterior wall, the baseline risk of spreading only into the para-aortic area increased significantly in selected patients at risk of nodal disease.

Optimal management of breast cancer with physical exam negative/radiological abnormal axilla.

For breast cancer patients with physical exam node negative but radiological finding node abnormal (cN0/rNa), the NCCN and ASCO guidelines recommend sentinel lymph node biopsy (SLNB) as the first-line axillary staging. However, patients who undergo surgery firstly may be upstaged to pathological II-III status, and these patients happen to be the adaptive population of neoadjuvant therapy (NAT). There is no consensus on the optimal management of cN0/rNa patients. The aim is to explore the optimal management strategy of these patients. We performed a retrospective real-world study of 1414 cN0/rNa patients from June 2014 to October 2022. There were 1003 patients underwent surgery first and 411 patients underwent surgery after NAT. We analyzed the real-world conditions of these patients, compared axilla tumor burden between these two groups. In addition, we compared benefit ratio of axillary surgery and regional nodal irradiation (RNI) de-escalation under the two strategies. Among 1003 patients underwent surgery first, the positive and negative rates of fine needle aspiration (FNA) were 18.5% and 81.5%, respectively. There were 66.1% had ≤ 2 lymph nodes+. There were 40.8% of FNA+ patients could be exempted from ALND underwent surgery first. In 411 patients underwent surgery after NAT, the FNA positive and negative rates were 60.8% and 49.2%, respectively. There were 54.4% of FNA+ patients achieved axilla pathologic complete response (apCR) and could omit ALND after NAT. The apCR was 67.3% in HER2+/TNBC subtypes. According to the NSABP-B51 trial, there were 0 and 54.4% of FNA+ patients could omit RNI among surgery first and after NAT, respectively. Among 1-2 sentinel lymph node (SLN)-positive patients underwent surgery first, with a median follow-up 49 months, there was no difference of survival benefit between SLNB-only and SLNB-ALND. Compared with 1-2 SLN+ patients without RNI, RNI could bring better invasive disease-free survival (97.38% vs. 89.36%, P = 0.046) and breast cancer special survival (100% vs. 94.68%, P = 0.020). It is safe to perform SLNB omitting ALND when detected 1-2 positive SLNs in cN0/rNa patients. Patients with HER2+/TNBC subtypes underwent surgery after NAT had more chance to benefit from dual de-escalation, including axillary surgery and RNI de-escalation.

Use of the SNOWED Dataset for Sentinel-2 Remote Sensing of Water Bodies: The Case of the Po River.

The paper demonstrates the effectiveness of the SNOWED dataset, specifically designed for identifying water bodies in Sentinel-2 images, in developing a remote sensing system based on deep neural networks. For this purpose, a system is implemented for monitoring the Po River, Italy's most important watercourse. By leveraging the SNOWED dataset, a simple U-Net neural model is trained to segment satellite images and distinguish, in general, water and land regions. After verifying its performance in segmenting the SNOWED validation set, the trained neural network is employed to measure the area of water regions along the Po River, a task that involves segmenting a large number of images that are quite different from those in SNOWED. It is clearly shown that SNOWED-based water area measurements describe the river status, in terms of flood or drought periods, with a surprisingly good accordance with water level measurements provided by 23 in situ gauge stations (official measurements managed by the Interregional Agency for the Po). Consequently, the sensing system is used to take measurements at 100 "virtual" gauge stations along the Po River, over the 10-year period (2015-2024) covered by the Sentinel-2 satellites of the Copernicus Programme. In this way, an overall space-time monitoring of the Po River is obtained, with a spatial resolution unattainable, in a cost-effective way, by local physical sensors. Altogether, the obtained results demonstrate not only the usefulness of the SNOWED dataset for deep learning-based satellite sensing, but also the ability of such sensing systems to effectively complement traditional in situ sensing stations, providing precious tools for environmental monitoring, especially of locations difficult to reach, and permitting the reconstruction of historical data related to floods and draughts. Although physical monitoring stations are designed for rapid monitoring and prevention of flood or other disasters, the developed tool for remote sensing of water bodies could help decision makers to define long-term policies to reduce specific risks in areas not covered by physical monitoring or to define medium- to long-term strategies such as dam construction or infrastructure design.

Discordance between peritumoral and subareolar injections for mapping sentinel lymph nodes in the breast.

PURPOSE: Sentinel node biopsy (SNB) is a common staging tool for breast cancer. Initially, peritumoral (PT) injections were used, however subareolar (SA) injections were later introduced to simplify the technique. Controversy remains regarding whether PT and SA injections map the same sentinel lymph nodes (SLNs). This study aimed to determine whether the regional location of breast SLNs differs when using PT versus SA injections using a large dataset from a single institution. METHODS: A total of 1035 patients who underwent breast SNB (PT injections: n = 858 and SA injections: n = 177) with lymphoscintigraphy and SPECT/CT were included. The identified SLN locations using SA injections were compared with those using PT injections. Differences in drainage proportions and odds ratios (ORs) for each clockface breast region and the whole breast were calculated using a two-proportion z-test and Fisher's Exact Test. RESULTS: A higher proportion of internal mammary SLNs were identified using PT injections for the whole breast (0.30 versus 0.09) and for all breast regions, with all regions showing statistical significance except the upper outer quadrant. Similarly, ORs showed identification of internal mammary SLNs was significantly higher when using PT injections (4.35, 95% CI 2.53 to 7.95). There were no significant differences in identifying axillary SLNs between injection sites. CONCLUSION: This is the largest cohort study to compare the regional location of breast SLNs identified using PT injections versus SA injections. Discordance was shown in the SLNs identified between injection techniques, with PT injections more frequently identifying internal mammary SLNs.

Comparison of conventional and machine learning regression models for accurate prediction of selected optical active components - A case study: The Gulf of Izmit.

This study hypothesizes that advanced machine learning (ML) models can more accurately predict certain critical water quality parameters in marine environments compared to conventional regression techniques. We specifically evaluated the spatio-temporal distribution of Chlorophyll-a (Chl-a) and Secchi Disk Depth (SDD) in the Gulf of Izmit using in-situ measurements and Sentinel-2 satellite imagery from October 2021 and 2022. Among the models tested, the Support Vector Regression (SVR) model showed better predictive performance, achieving the lowest RMSE for SDD (1.11-1.70 m) and Chl-a (1.16-4.97 mg/m3) and the lowest MAE for SDD (0.86-1.43 m) and Chl-a (1.03-3.17 mg/m3). Additionally, the study observed a shift from hypertrophic to eutrophic Chl-a conditions and from mesotrophic-eutrophic to oligotrophic SDD conditions between 2021 and 2022, aligning with SVR model predictions and in-situ observations. These findings underscore the potential of ML models to enhance the accuracy of water quality monitoring and management in marine ecosystems.

Skin Staining After Injection of Superparamagnetic Iron Oxide for Sentinel Lymph Node Dissection: A Retrospective Study of Two Protocols for Injection and Long-Term Follow-Up.

OBJECTIVE: Sentinel lymph node (SLN) dissection is a highly accurate surgical procedure allowing detection of lymph node invasion in patients with clinically negative axilla in early breast cancer. Superparamagnetic iron oxide (SPIO) is a marker used during SLN procedure, allowing the same detection rate as isotopes (Tc-99). A drawback of SPIO is skin staining that can occur around the injection site. The goal of this retrospective study was to assess the frequency of skin staining after oncological breast surgery with SPIO, and the impact of two different injection protocols on the rate of skin staining. MATERIALS AND METHODS: Data from breast cancer patients undergoing magnetic tracer SLN detection (SLND) procedure in a single department between 2020 and 2022 was reviewed. Injection protocol P1 consisted of retro-areolar injection of Magtrace 0.8 mL. Injection protocol P2, consisted of retro-tumoral injection with 1 mL. Presence of skin staining was assessed at day 10 after surgery. The evolution and satisfaction of the patients was assessed at six and 12 months. RESULTS: In total 175 sentinel lymph node biopsy procedures were performed (P1: 141/P2: 34), consisting of breast conservative surgery (BCS) (P1: 70%/P2: 53%) or mastectomy (P1: 30%/P2: 47%) with SLN. SLN detection rate was 97.7%. Skin staining was reported in 23% and occurred more often after BCS (31.6%) compared to mastectomy (6.8%). When BCS was performed, peritumoral injection was associated with a decreased risk of skin staining compared with retro-areolar injection (22.2% vs. 33.3%, respectively). When present skin staining persisted for 12 months, but most of the patients described only a slight discomfort. The low rate of discoloration after mastectomy, as previously reported, can be explained by the removal of skin and glandular tissue in which the tracer accumulates. Less skin staining in P2 may be because of a shorter interval between injection and surgery and the removal of the excess of SPIO during the lumpectomy. CONCLUSION: SPIO injection is a safe surgical technique. After mastectomy, the rate of discoloration was low. Despite the persistent skin discoloration in 58.6% in our study, patient satisfaction was high. Deeper injection, reduced doses, massage of the injection site and peritumoral injection may reduce skin staining.

Conservative Management of Vulvar Cancer-Where Should We Draw the Line?

Vulvar cancer is a rare disease, and cure rates were low until the mid-20th century. The introduction of an en bloc radical vulvectomy and bilateral groin and pelvic lymph node dissection saw them rise from 15-20% to 60-70%. However, this very radical surgery was associated with high physical and psychological morbidity. Wounds were usually left open to granulate, and the average post-operative hospital stay was about 90 days. Many attempts have been made to decrease morbidity without compromising survival. Modifications that have proven to be successful are as follows: (i) the elimination of routine pelvic node dissection, (ii) the use of separate incisions for groin dissection, (iii) the use of unilateral groin dissection for lateral, unifocal lesions, (iv) and radical local excision with 1 cm surgical margins for unifocal lesions. Sentinel node biopsy with ultrasonic groin surveillance for patients with node-negative disease has been the most recent modification and is advocated for patients whose primary cancer is <4 cm in diameter. Controversy currently exists around the need for 1 cm surgical margins around all primary lesions and on the appropriate ultrasonic surveillance for patients with negative sentinel nodes.

Retrieval of the Clipped Axillary Lymph Node and Its Impact on Treatment Decisions.

We examined clinically node-positive (cN+) breast cancer patients undergoing neoadjuvant chemotherapy and clipped lymph node (CLN) localization to determine the rate of CLN = non-sentinel lymph node (SLN), the factors associated with cN+ to pN0 conversion, and the treatment impact. We conducted a single institution review of cN+ patients receiving NAC from 2016 to 2022 with preoperative CLN localization (N = 81). Demographics, hormone receptor (HR) and HER2 status, time to surgery, staging, chemotherapy regimen, localization method, pathology, and adjuvant therapy were analyzed. Pathologic complete response (pCR) of the CLN was observed in 41 patients (50.6%): 18.8% HR+/HER2-, 75% HR+/HER2+, 75% HR-/HER2+, and 62.5% triple-negative breast cancer (p-value = 0.006). CLN = SLN in 68 (84%) patients, while CLN = non-SLN in 13 (16%). In 14 (17.3%) patients, the final treatment was altered based on +CLN status: 11 patients underwent axillary lymph node dissection (ALND), and 3 had systemic treatment changes. pCR rates varied, with the highest conversion rates observed in HER2+ disease and the lowest in HR+/HER2- disease. In 2 (2.5%) patients, adjuvant therapy changes were made based on a non-sentinel CLN, while in 97.5% of patients, a SLN biopsy alone represented the status of the axilla. This demonstrates that a +CLN often alters final plans and that, despite also being a SLN in most cases, a subset of patients will be undertreated by SLN biopsy alone.

Impact of Indocyanine Green Dose on Sentinel Lymph Node Mapping in Cervical Cancer: A Systematic Review.

Over the past decade, SLN mapping has become increasingly important in cervical cancer surgery. ICG is the most commonly used tracer due to its high bilateral detection rates, ease of use, and safety. However, there is no consensus on the optimal ICG dose, leading to variability in outcomes. This systematic review aims to evaluate the impact of different ICG doses on SLN detection in early-stage cervical cancer, identifying the most effective and safe dose for clinical practice. A comprehensive search was conducted in MEDLINE/PubMed up to May 2024. Studies included assessed SLN mapping using ICG in stage IA2-IIA/IIB cervical cancer. Exclusions were applied to studies not reporting ICG dose or using multiple tracers without dose-specific results. Twelve studies were included, with ICG concentrations ranging from 0.25 mg/mL to 25 mg/mL and injection volumes from 1 to 10 mL. Overall SLN detection rates ranged from 88% to 100%, while bilateral detection rates varied between 74.1% and 98.5%. The most consistent results were obtained with an ICG concentration of 1.25 mg/mL and a 4 mL injection volume. In conclusion, an ICG concentration of 1.25 mg/mL with a 4 mL injection volume is recommended for effective SLN mapping in cervical cancer, achieving high detection rates with minimal variability. Standardizing this dose in clinical practice is suggested to improve reproducibility and outcomes.

Role of CD44-Positive Extracellular Vesicles Derived from Highly Metastatic Mouse Mammary Carcinoma Cells in Pre-Metastatic Niche Formation.

Malignant breast cancers pose a notable challenge when it comes to treatment options. Recently, research has implicated extracellular vesicles (EVs) secreted by cancer cells in the formation of a pre-metastatic niche. Small clumps of CD44-positive breast cancer cells are efficiently transferred through CD44-CD44 protein homophilic interaction. This study aims to examine the function of CD44-positive EVs in pre-metastatic niche formation in vitro and to suggest a more efficacious EV formulation. We used mouse mammary carcinoma cells, BJMC3879 Luc2 (Luc2 cells) as the source of CD44-positive EVs and mouse endothelial cells (UV2 cells) as the recipient cells in the niche. Luc2 cells exhibited an enhanced secretion of EVs expressing CD44 and endothelial growth factors (VEGF-A, -C) under 20% O2 (representative of the early stage of tumorigenesis) compared to its expression under 1% O2 (in solid tumor), indicating that pre-metastatic niche formation occurs in the early stage. Furthermore, UV2 endothelial cells expressing CD44 demonstrated a high level of engulfment of EVs that had been supplemented with hyaluronan, and the proliferation of UV2 cells occurred following the engulfment of EVs. These results suggest that anti-VEGF-A and -C encapsulated, CD44-expressing, and hyaluronan-coated EVs are more effective for tumor metastasis.

Pelvic Sentinel Lymph Node Biopsy for Endometrial Cancer with Multi-Modal Infrared Signal Technology: A Video Article.

This video article summarizes a case study involving the use of pelvic sentinel lymph node (SLN) biopsy for endometrial cancer (EC) staging and treatment utilizing a multi-modal infrared signal technology. This innovative approach combines cervical injection of fluorescent dye indocyanine green (ICG) and near-infrared imaging to enhance SLN detection rates in early-stage EC patients. The study showcases the successful application of advanced technology in improving surgical staging procedures and reducing postoperative morbidity for patients. Multi-modal infrared signal technology consists of different modes of fluorescence imaging used to identify lymph nodes based on near-infrared signals. Each mode serves a specific purpose: overlay image combines white light and near-infrared signals in green, monochromatic visualization shows near-infrared signal in greyscale, and intensity map combines signals in a color scale to differentiate signal intensity. Yellow denotes strong near-infrared signals while blue represents weaker signals. By utilizing a multi-modal approach, surgeons can accurately identify and remove SLN, thus avoiding unnecessary removal of secondary or tertiary echelons.