Non-metastatic Nodes Research Articles

Application of dielectric properties for identification of normal and malignant gastrointestinal tumors and lymph nodes ex vivo.

A need exists for a quick, simple method to accurately assess resection margins and lymph node metastases in gastrointestinal cancer surgeries. We aimed to develop a real-time, non-destructive technique to differentiate between normal and cancerous tissues using dielectric properties. Dielectric properties of tissues from 50 gastric and 120 colorectal cancer patients were measured during surgery using an open-ended coaxial probe, spanning frequencies from 10MHz to 4GHz. Lymph nodes were classified based on pathology into metastatic and non-metastatic, and tissues were divided into cancerous and normal, the latter being 3cm from the cancer edge. Statistically significant differences in dielectric properties were found between metastatic and non-metastatic lymph nodes (P < 0.05), and between normal and malignant tissues. Metastatic lymph nodes showed higher dielectric permittivity and conductivity across the frequency range, with no significant difference between gastric and colorectal cancers. The coaxial probe method distinguishes between metastatic and non-metastatic lymph nodes by their dielectric properties within 10-4000MHz, offering a potential tool for real-time identification of malignant tissues during surgery, despite not identifying the cancer type.

Role of Diffusion-Weighted Magnetic Resonance Imaging in Detection of Lymph Node Metastasis in Rectal Cancer

Abstract Background Rectal cancer is one of the most common malignancies of the digestive tract, ranking first in the worldwide incidence of malignant tumors. The early diagnosis, accurate staging and early treatment of rectal cancer are key to improve the five-year survival rate. Rectal MRI plays a crucial role in evaluating rectal cancer by providing multiple prognostic findings and imaging features that guide proper patient management. Aim of the Work to evaluate the performance of diffusion-weighted MRI (DWI) for the detection of lymph nodes and for differentiating between benign and metastatic nodes during primary rectal cancer staging. Patients and Methods the study was carried out at Ain Shams University Hospitals, Radiodiagnosis Department on 35 patients, 29 patients were histopathologically proven rectal carcinoma underwent surgical resection and 6 cases were potentially free of cancer considered as control. Results We found that the size of metastatic lymph nodes on DWI was significantly larger than that of non-metastatic lymph nodes (0.97± 0.37 vs. 0.4± 0.17 cm), most of malignant nodes had rounded shape (55.6 %) vs. oval shaped (70.6%) in benign nodes and almost all of metastatic lymph nodes had irregular margin (97.2%) while all benign nodes appeared having smooth margin. The mean ADC value was significantly lower for metastatic lymph nodes than non-metastatic lymph nodes (1.21± 0.54 vs. 1.51± 0.51 x 103 mm²/sec). In addition, for evaluation of lymph node metastasis that reflects the primary tumor characteristics, the LN/T ratio (defined as the ratio of lymph node ADC value to the primary tumor ADC value) was calculated. It was significantly lower for metastatic lymph nodes than non-metastatic lymph nodes (1.06± 0.37 vs. 1.65± 0.73). Receiver operating characteristic curve analysis revealed that the best performing cutoffs were 0.5 cm for lymph node size, 0.987 x 103 mm²/ sec for ADC value, and 0.762 for LN/T ratio. Accuracy was significantly greater for lymph nodes with irregular margin (92.3%), than LN/T ratio (78.5%) than for lymph node size (62.0%) or ADC value (74.8%). Conclusion Preoperative DWI, especially the margin of lymph nodes as well as LN/T ADC ratio, are recommended for evaluation of lymph node metastasis in patient with rectal cancer.

Diffusion-Weighted Magnetic Resonance Imaging for the Diagnosis of Lymph Node Metastasis in Patients with Biliary Tract Cancer.

Objective: The diagnostic efficacy of the apparent diffusion coefficient (ADC) in diffusion-weighted magnetic resonance imaging (DW-MRI) for lymph node metastasis in biliary tract cancer was investigated in the present study. Methods: In total, 112 surgically resected lymph nodes from 35 biliary tract cancer patients were examined in this study. The mean and minimum ADC values of the lymph nodes as well as the long-axis and short-axis diameters of the lymph nodes were assessed by computed tomography (CT). The relationship between these parameters and the presence of histological lymph node metastasis was evaluated. Results: Histological lymph node metastasis was detected in 31 (27.7%) out of 112 lymph nodes. Metastatic lymph nodes had a significantly larger short-axis diameter compared with non-metastatic lymph nodes (p = 0.002), but the long-axis diameter was not significantly different between metastatic and non-metastatic lymph nodes. The mean and minimum ADC values for metastatic lymph nodes were significantly reduced compared with those for non-metastatic lymph nodes (p < 0.001 for both). However, the minimum ADC value showed the highest accuracy for the diagnosis of histological lymph node metastasis, with an area under the curve of 0.877, sensitivity of 87.1%, specificity of 82.7%, and accuracy of 83.9%. Conclusions: The minimum ADC value in DW-MRI is highly effective for the diagnosis of lymph node metastasis in biliary tract cancer. Accurate preoperative diagnosis of lymph node metastasis in biliary tract cancer should enable the establishment of more appropriate treatment strategies.

Reference gene evaluation for normalization of gene expression studies with lymph tissue and node‑derived stromal cells of patients with oral squamous cell carcinoma.

Profiling studies using reverse transcription quantitative PCR (RT-qPCR) require reliable normalization to reference genes to accurately interpret the results. A stable reference gene panel was established to profile metastatic and non-metastatic lymph nodes in patients with oral squamous cell carcinoma. The stability of 18S ribosomal RNA (18SrRNA), ribosomal Protein Lateral Stalk Subunit P0 (RPLP0), ribosomal Protein L27 (RPL27), TATA-box binding protein (TBP), hypoxanthine phosphoribosyl-transferase 1 (HPRT1), beta-actin (ACTB), glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) and vimentin (VIM) was evaluated, as reference genes for profiling patient-derived lymph node stromal cells (LNSCs; N=8; N0:6, N+:2) and lymph node tissues (Patients:14, Nodes=20; N0:7; N+:13). The genes were initially assessed based on their expression levels, specificity, and stability rankings to identify the best combination of reference genes. VIM was excluded from the final analysis because of its low expression (high quantification cycle >32) and multiple peaks in the melting curve. The stability analysis was performed using Reffinder, which utilizes four tools; geNorm, NormFinder, BestKeeper and Comparative ∆Ct methods, thereby enabling the computing of a comprehensive ranking. Evaluation of the gene profiles indicated that while RPLP0 and 18SrRNA were stable in both lymph node tissues and LNSCs, HPRT1, RPL27 were uniquely stable in these tissues whereas ACTB and TBP were most stable in LNSCs. The present study identified the most stable reference gene panel for the RT-qPCR profiling of lymph node tissues and patient-derived LNSCs. The observation that the gene panel differed between the two model systems further emphasized the need to evaluate the reference gene subset based on the disease and cellular context.

Assessment of Immunoreactivity Patterns in the Excised Cervical Lymph Nodes of Oral Squamous Cell Carcinoma

Introduction: Epidermoid carcinoma (oral squamous cell carcinoma [OSCC]) comprises approximately 80% of the malignancies of the oral cavity, which is also responsible for the morbidity and mortality due to the distant spread of the neoplastic cells. The regional draining lymph node has been considered an anatomic barrier to the systemic dissemination of malignant cells. It has been postulated that the microscopic architectural pattern of a regional lymph node (RLn) represents the immunologic reactivity in that node and the host response. Morphological assessment of the regional nodes aids in a better understanding of the immune response and its correlation with the stage of the tumour. Materials and Methods: A total of 51 head-and-neck dissection cases were assessed for immunomorphological patterns and the degree of tumour involvement in positive lymph nodes. 49 lymph nodes were in the early stage (TNM Stage l and ll) and 71 lymph nodes were in the advanced stage(TNM stage lll and lV). A total of 595 lymph nodes were histologically evaluated and were categorised into metastatic and non-metastatic nodes showing four different patterns: lymphocyte predominance (LP) pattern, germinal centre predominance (GCP) pattern, sinus histiocytosis (SH) pattern and lymphocyte-depleted pattern. Results: The most frequently encountered pattern of lymph nodes was of LP (436 nodes), followed by GCP (61 nodes), SH (36 nodes) and lymphocyte depleted (18 nodes), respectively. Out of 595, 120 nodes were positive for metastasis, indicating that as the stage advances, the GCP type predominates (the predominant immunomorphological pattern shifts from LP to GCP), facilitating metastasis. Conclusion: Immunomorphological changes in the RLns of OSCCs seem to be pivotal factors that serve as an important prognostic indicator. Whereas the cell-mediated immune response represented by LP and SH appears to resist the metastasis process, the humoral response reflected by GCP favours metastasis.

Quantitative analysis of peri-intestinal lymph node metastasis using indocyanine green fluorescence imaging technology.

We evaluated the efficacy of indocyanine green fluorescence imaging compared to that of traditional nanocarbon dyes in assessing peri-intestinal lymph node metastasis in patients with colorectal cancer, which is a key prognostic factor. The relationship between indocyanine green fluorescence imaging and histopathological outcomes in patients with colon cancer has also been explored. A retrospective analysis was conducted on 30 patients with colon cancer (from May to October 2023) confirmed by surgical pathology. Tumors were marked with indocyanine green (ICG) or nanocarbon via colonoscopy 16 to 24 hours before surgery. Within 15 minutes after surgery, peri-intestinal lymph node fluorescence imaging and hematoxylin and eosin staining were used to assess the distribution of cancer foci. The correlation between cancer foci distribution, fluorescence intensity, and area under the receiver operating characteristic curve was measured. Among 243 metastatic lymph nodes from 30 patients, 18 were found. After the patients were divided into metastatic and nonmetastatic groups, significant differences in tumor differentiation and stage were noted (P < .001). The fluorescence intensity was strongly correlated with the presence and proportion of metastasis (area under the receiver operating characteristic curve = 0.931), whereas nanocarbon staining showed no significant correlation (P = .81). All P values were two-sided, with P < .05 indicating statistical significance. Lymph nodes with malignant intestinal tumor metastasis displayed weaker ICG fluorescence than did nonmetastatic nodes. Combining ICG and nanocarbon staining techniques enhances intraoperative lymph node dissection and postoperative analysis, indicating their potential utility in colorectal cancer surgery.

Intra-patient spatial comparison of non-metastatic and metastatic lymph nodes reveals the reduction of CD169+ macrophages by metastatic breast cancers

Breast cancer cells suppress the host immune system to efficiently invade the lymph nodes; however, the underlying mechanism remains incompletely understood. Here, we aimed to comprehensively characterise the effects of breast cancers on immune cells in the lymph nodes. We collected non-metastatic and metastatic lymph node samples from 6 patients with breast cancer with lymph node metastasis. We performed bulk transcriptomics, spatial transcriptomics, and imaging mass cytometry to analyse the obtained lymph nodes. Furthermore, we conducted histological analyses against a larger patient cohort (474 slices from 58 patients). The comparison between paired lymph nodes with and without metastasis from the same patients demonstrated that the number of CD169+ lymph node sinus macrophages, an initiator of anti-cancer immunity, was reduced in metastatic lymph nodes (36.7±21.1 vs 7.3±7.0cells/mm2, p=0.0087), whereas the numbers of other major immune cell types were unaltered. We also detected that the infiltration of CD169+ macrophages into metastasised cancer tissues differed by section location within tumours, suggesting that CD169+ macrophages were gradually decreased after anti-cancer reactions. Furthermore, CD169+ macrophage elimination was prevalent in major breast cancer subtypes and correlated with breast cancer staging (p=0.022). We concluded that lymph nodes with breast cancer metastases have fewer CD169+ macrophages, which may be detrimental to the activity of anti-cancer immunity. JSPS KAKENHI (16H06279, 20H03451, 20H04842, 22H04925, 19K16770, and 21K15530, 24K02236), JSPS Fellows (JP22KJ1822), AMED (JP21ck0106698), JST FOREST (JPMJFR2062), Caravel, Co., Ltd, Japan Foundation for Applied Enzymology, and Sumitomo Pharma Co., Ltd. under SKIPS.

Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Positron Emission Tomography (PET) for Distinguishing Metastatic Lymph Nodes from Nonmetastatic Among Patients with Rectal Cancer: A Systematic Review and Meta-Analysis

Abstract Objective The objective of this research was to assess the proficiency of quantitative dynamic contrast-enhanced magnetic resonance imaging (QDCE-MRI) and positron emission tomography (PET) imaging in distinguishing between metastatic and nonmetastatic lymph nodes in cases of rectal carcinoma. Method This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. Two independent reviewers systematically searched databases including PubMed, Embase, Web of Science, and the Cochrane Library. The research took place in July 2022, with no restriction on the initial date of publication. For the analysis, we utilized Stata software (version 16.0), Review Manager (version 5.3), and the Open Meta-Analyst computational tool. Results A total of 19 studies consisting of 1,451 patients were included in the current meta-analysis. The differences between metastatic and nonmetastatic lymph node parameters were significant by using short axis and Ktrans (6.9 ± 4 vs. 5.4 ± 0.5, 0.22 ± 0.1 vs. 0.14 ± 0.1, respectively). Contrast-enhanced MRI (CE-MRI) showed 73% sensitivity, 71% specificity, and 79% accuracy in detecting metastatic lymph nodes among rectal cancer patients based on six included studies (n = 530). The overall sensitivity, specificity, and accuracy of QDCE-MRI using Ktrans was calculated to be 80, 79, and 80%, respectively. Furthermore, PET-computed tomography (CT) showed a sensitivity of 80%, specificity of 91%, and accuracy of 86% in distinguishing metastatic lymph nodes. Quality utility analysis showed that using CE-MRI, QDCE-MRI, and PET-CT would increase the posttest probability to 69, 73, and 85%, respectively. Conclusion QDCE-MRI demonstrates a commendable sensitivity and specificity, but slightly overshadowed by the higher specificity of PET-CT at 91%, despite comparable sensitivities. However, the heterogeneity in PET-CT sensitivity across studies and its high specificity indicate variability that can influence clinical decision-making. Thus, combining these imaging techniques and perhaps newer methods like PET/MRI could enhance diagnostic accuracy, reduce variability, and improve patient management strategies in rectal cancer.

The value of net influx constant based on FDG PET/CT dynamic imaging in the differential diagnosis of metastatic from non-metastatic lymph nodes in lung cancer.

This study aims to evaluate the value of the dynamic and static quantitative metabolic parameters derived from 18F-fluorodeoxyglucose (FDG)-positron emission tomography/CT (PET/CT) in the differential diagnosis of metastatic from non-metastatic lymph nodes (LNs) in lung cancer and to validate them based on the results of a previous study. One hundred and twenty-one patients with lung nodules or masses detected on chest CT scan underwent 18F-FDG PET/CT dynamic + static imaging with informed consent. A retrospective collection of 126 LNs in 37 patients with lung cancer was pathologically confirmed. Static image analysis parameters include LN-SUVmax and LN-SUVmax/primary tumor SUVmax (LN-SUVmax/PT-SUVmax). Dynamic metabolic parameters including the net influx rate (Ki) and the surrogate of perfusion (K1) and of each LN were obtained by applying the irreversible two-tissue compartment model using in-house Matlab software. Ki/K1 was then calculated as a separate marker. Based on the pathological findings, we divided into a metastatic group and a non-metastatic group. The χ2 test was used to evaluate the agreement of the individual and combined diagnosis of each metabolic parameter with the gold standard. The receiver-operating characteristic (ROC) analysis was performed for each parameter to determine the diagnostic efficacy in differentiating non-metastatic from metastatic LNs with high FDG-avid. P < 0.05 was considered statistically significant. Among the 126 FDG-avid LNs confirmed by pathology, 70 LNs were metastatic, and 56 LNs were non-metastatic. For ROC analysis, in separate assays, the dynamic metabolic parameter Ki [sensitivity (SEN) of 84.30%, specificity (SPE) of 94.60%, accuracy of 88.89%, and AUC of 0.895] had a better diagnostic value than the static metabolic parameter SUVmax (SEN of 82.90%, SPE of 62.50%, accuracy of 74.60%, and AUC of 0.727) in differentiating between metastatic from non-metastatic LNs groups, respectively. In the combined diagnosis group, the combined SUVmax + Ki diagnosis had a better diagnostic value in the differential diagnosis of metastatic from non-metastatic LNs, with SEN, SPE, accuracy, and AUC of 84.3%, 94.6%, 88.89%, and 0.907, respectively. When the cutoff value of Ki was 0.022ml/g/min, it had a high diagnostic value in the differential diagnosis between metastasis and non-metastasis in FDG-avid LNs of lung cancer, especially in improving the specificity. The combination of SUVmax and Ki is expected to be a reliable metabolic parameter for N-staging of lung cancer.

Elevated Cancer-Associated Hyaluronan Correlates With Diagnosis and Lymph Node Metastasis of Papillary Thyroid Cancer

The glycosaminoglycan hyaluronan (HA) plays an important role in tumor progression. However, its biological and clinical significance in papillary thyroid cancer (PTC) remains unknown. Immunohistochemistry was performed to examine HA expression in tissues from PTC patients. Two PTC cell lines were treated with HA synthesized inhibitor against HA production to assess its function. Serum HA levels from 107 PTC patients, 30 Hashimoto thyroiditis patients, and 45 normal controls (NC) were measured by chemiluminescence immunoassay. HA levels in fine needle aspiration (FNA) washouts obtained from thyroid nodules and lymph nodes (LNs) were measured by chemiluminescence immunoassay. Area under the curve (AUC) was computed to evaluate HA’s clinical value. HA was highly expressed in PTC. Reducing HA production significantly inhibited PTC cell proliferation and invasion. Importantly, serum HA levels in PTC were significantly higher than those in NCs and Hashimoto thyroiditis and allowed distinguishing of thyroid cancers from NCs with high accuracy (AUC = 0.782). Moreover, elevated serum HA levels in PTC correlate with LN metastasis. HA levels in FNA washouts from PTC patients were significantly higher than those in benign controls, with a high AUC value (0.8644) for distinguishing PTC from benign controls. Furthermore, HA levels in FNA washouts from metastatic LN were significantly higher than those in nonmetastatic LN, with a high AUC value (0.8007) for distinguishing metastatic LNs from nonmetastatic LNs. HA levels in serum and FNA washout exhibited a potential significance for PTC diagnosis and an indicator for LN metastasis in patients with PTC.

Texture analysis of ultrasonography to differentiate metastatic from nonmetastatic cervical lymph nodes in mandibular gingival squamous cell carcinoma

AbstractAimThis study aimed to distinguish between metastatic and nonmetastatic cervical lymph nodes (CLNs) in patients with mandibular gingival squamous cell carcinoma using texture analysis of lymph nodes on ultrasonography images.MethodsA total of 29 metastatic and 34 nonmetastatic CLNs were selected for this study. Fifty‐six texture characteristics were retrieved from the ultrasonography images using the LIFEx software.The Mann–Whitney U test was used to evaluate measurable differences in texture characteristics between metastatic and nonmetastatic CLNs. The ability of the surface features to distinguish between metastatic and nonmetastatic CLNs was illustrated using receiver operating characteristic curves. Youden's J statistic was used to determine the receiver operating characteristic curve cutoff values with maximal sensitivity and specificity.ResultsGray‐level nonuniformity, run length nonuniformity, coarseness, strength, and zone size nonuniformity showed the most notable contrast between the metastatic and nonmetastatic CLNs (p &lt; 0.001). Zone size nonuniformity showed an area under the curve value of 0.827, sensitivity of 0.645, and specificity of 0.972 at the cutoff value of 1010.538.ConclusionQualitative characteristics may be the optimal surface features to distinguish between metastatic and nonmetastatic CLNs and predict CLN metastasis in patients with mandibular gingival squamous cell carcinoma.

The value of synthetic MRI for quantitative analysis in the diagnosis of cervical lymph node metastasis in thyroid cancer.

Preoperative effective assessment of cervical lymph node metastasis in thyroid cancer plays an important role in formulating the surgical plan. To investigate the significance of synthetic magnetic resonance imaging (MRI) for quantitatively analyzing cervical lymph node metastasis in thyroid cancer. A retrospective analysis was conducted on 30 patients with thyroid cancer, consisting of 19 thyroid cancer nodules, 45 metastatic lymph nodes, and 47 non-metastatic lymph nodes. Regions of interest (ROIs) for each type of nodule were manually delineated using a workstation. Quantitative parameters, such as T1, T2, and proton density (PD) values, were automatically extracted from synthetic MRI scans. Statistical tests and regression analysis were performed to assess differences and correlations among the quantitative parameters. There were no significant differences in the quantitative parameter values between the primary tumor and metastatic lymph node tissues (P > 0.05). However, significant differences were observed in the quantitative parameters between the primary tumor and non-metastatic lymph node tissues and between the metastatic and non-metastatic lymph node tissues (P < 0.05). The diagnostic accuracy for cervical lymph node metastasis in thyroid cancer was 94.4% for the T1 and T2 combined index, 91.9% for T2, 86.8% for T1, and 71.7% for PD values. The application of quantitative parameters from synthetic MRI can assist clinicians in accurately planning surgical interventions for thyroid cancer patients before surgery.

Spectral CT for preoperative diagnosis of N2 station lymph node metastasis in solid T1 non-small cell lung cancer

PurposeTo evaluate the diagnostic value of spectral CT for the preoperative diagnosis of N2 station lymph nodes metastasis in solid T1 non-small cell lung cancer (NSCLC). MethodFor this retrospective study, dual-phase contrast agent-enhanced CT was performed in patients with NSCLC from September 2019 to June 2023. Quantitative spectral CT parameters measurements were performed by 2 radiologists independently. Logistic regression analysis and Delong test were performed. Results60 NSCLC patients (mean age, 62.85 years ± 8.49, 44men) were evaluated. A total of 121 lymph nodes (38 with metastasis) were enrolled. There was no significant difference in the slope of the spectral Hounsfield unit curve (λHu) on arterial phase (AP) or venous phase (VP) between primary lesions and metastatic lymph nodes (P > 0.05), but significant difference in VP λHu between primary lesions and non-metastatic lymph nodes (P < 0.001). The CT40KeV, λHu, normalized iodine concentration (nIC), normalized effective atomic number (nZeff) measured during both AP and VP were lower in metastatic lymph nodes than in non-metastatic lymph nodes (all P < 0.05). Short-axis diameter (S) of metastatic lymph nodes was higher than non-metastatic lymph nodes (P < 0.001). Area under the curve (AUC) for S performed the highest (0.788) in diagnosing metastatic lymph nodes. When combined with VP λHu, VP nZeff, AUC increased to 0.871. ConclusionSpectral CT is a complementary means for the preoperative diagnosis of N2 station lymph nodes metastasis in solid T1 NSCLC. The combined parameters have higher diagnostic efficiency.

MRI Texture Analysis of Inguinal Lymph Node Metastasis in Vulvar Cancer - Associations With Histopathology.

Texture analysis is a quantitative imaging technique that provides novel biomarkers beyond conventional image reading. This study aimed to investigate the correlation between texture parameters and histopathological features of lymph nodes in patients with vulvar cancer. Overall, nine female patients (mean age 70.1±13.4 years, range=39-87 years) were included in the analysis. All patients had squamous cell carcinomas and underwent upfront surgery with inguinal lymph node resection. Immunohistochemical assessment was performed using several markers of the epithelial-mesenchymal transition. The presurgical magnetic resonance imaging (MRI) was analyzed with the MaZda package. In discrimination analysis, several parameters derived from T1-weighted images showed statistically significant differences between non-metastatic and metastatic lymph nodes. The highest statistical significance was reached by the texture feature "S(0,3)InvDfMom" (p=0.016). In correlation analysis, significant associations were found between MRI texture parameters derived from both T1-weighted and T2-weighted images and the investigated histopathological features. Notably, S(0,3)InvDfMom derived from T1-weighted images highly correlated with the Vimentin-score (r=0.908, p=0.001). Several associations between MRI texture analysis and immunohistochemical parameters were identified in metastasized lymph nodes of cases with vulvar cancer.

Options to apply national developments in the assessment of sentinel lymph node involvement in breast cancer

Background. Breast cancer is the leading oncopathology of women. The routine radical surgery performed in this pathology includes lymph node dissection, which provokes development of postmastectomy syndrome. However, the removal of non-metastatic lymph nodes is not rational according to the subsequent disability of the patients. This can be avoided by using a sentinel lymph node (SLN) biopsy procedure. At this stage of oncology development, there are several ways to visualize SLN. The fluorescent method is among the most promising. This technique has been used for many years. However, it is not sufficiently implemented in clinical practice. There are still several questions about the procedure for its performance. In addition, it requires the introduction and improvement of domestic developments, including reducing financial costs.Aim. To study the use of indocyanine green of domestic production (LLC Firm “FERMENT”, Russia) and the IC-GOR detection system (LLC “MedKomplekt”, Russia) for SLN biopsy in patients with early breast cancer.Materials and methods. From February to September 2023, biopsy of SLN using indocyanine green (LLC Firm “FERMENT”, Russia) was performed in 53 patients with early breast cancer without clinically detectable lesion of regional lymph nodes. In all cases, according to the clinical examination, the patients had an operable stage of breast cancer (cT1–3N0M0). 5 mg of indocyanine green, dissolved in 4 ml of water for injection, was administered after sanitizing of the surgical field intradermally and subcutaneously at 2 points in the upper-outer quadrant of the breast along the edge of the areola in 40 patients (75.5 %) or paratumorally in 13 patients (24.5 %). An incision in the axilla about 4 cm long was made no earlier than 10–15 minutes after injection of indocyanine green (when visualizing the track 1 cm beyond its distal end to avoid crossing the lymph duct, after which the drug can flow into the wound). After imaging, all detected lymph nodes were removed for planned morphological examination. Standard lymph node dissection of 1 and 2 level was performed in all patients. Middle age of patients was 64.5 years (from 37 to 85 year). In 40 patients (75.5 %) modified radical mastectomy was performed, breast conserving surgery was done in 13 cases (24.5 %).Results. SLN were visualized in 51 patients out of 53 (96.2 %). After the final morphological examination, the majority of patients in the group were ranged in the IA and IIA stages of the disease – 15 (28.3 %) and 28 (52.8 %), respectively. Metastasis in the SLN were found in 9 patients (17.0 %). Besides, in 3 cases (5.7 %) metastasis in the lymph nodes were found after lymph node dissection. In 4 cases (7.6 %) metastasis were found during lymph node dissection but were not detected in the removed SLN. Thus, in the study group 13 (24.5 %) patients had metastatic lymph node lesion despite negative clinical status. The total number of removed SLN in the study group was 169 (from 1 to 6), the average number of removed lymph nodes was 3.3. Any negative events, allergic and general reactions to indocyanine were not reported.Conclusion. Our technique of contrasting SLN with indocyanine green is adequate and reproducible. The frequency of detection of SLN with this method is 96.2 %, with an acceptable level of false negative results is 7.6 %. Indocyanine green (LLC Firm “FERMENT”, Russia) and the LED fluoroscopic cancer detector IC-GOR (LLC “MedKomplekt”, Russia) can be recommended for performing a SLN biopsy.

Abstract PO4-25-01: Selective elimination of CD169+ macrophages in lymph nodes invaded by breast cancers

Abstract Lymph node metastasis is a prognostically significant factor in breast cancer, though the colonization mechanism of cancer cells in this immune cell-rich organ remains elusive. This study aimed to elucidate the impact of breast cancer on the lymph node immune cell landscape. Multiscale transcriptomic analyses were performed on both metastatic and non-metastatic lymph node samples from breast cancer patients with lymph node metastasis. Twenty laser-micro-dissected sections were obtained from 17 lymph nodes across six breast cancer patients at stages II–III, with each patient contributing both types of lymph nodes for direct comparison. Comparing the transcriptomes of paired lymph nodes with and without metastasis from the same patients revealed selective downregulation of CD169+ macrophage-related genes in metastatic lymph nodes. The spatial transcriptome indicated a potential depletion of CD169+ macrophages, initiators of anticancer immunity, from their residence (sinuses) in metastatic lymph nodes, while other principal immune cell types were unaltered. Mass spectrometry imaging revealed that the numbers of CD169+ macrophages were smaller in the metastatic lymph nodes than in the non-metastatic lymph nodes, suggesting that cancer cells uprooted CD169+ macrophages from the lymph nodes. Conversely, the count of B, T, Treg, and CD11c+ cells remained comparable in both lymph node types, albeit an enrichment of Treg cells around metastasized cancer tissues was observed. Additional immunohistochemistry analysis of 315 non-metastatic lymph nodes and 159 metastatic lymph nodes from 58 patients with breast cancer showed that a reduced CD169+ macrophage population was prevalent in various breast cancer subtypes. A subset of metastatic lymph nodes (37 out of 159) displayed a complete absence of detectable CD169+ macrophages. The data also depicted a gradual decline in CD169+ macrophages correlating with the pN classification, while no correlation was identified with pathological tumor size classification (pT) or metastasized cancer volume. The data suggest precedence of CD169+ macrophage elimination over other reported immune cell abnormalities, such as cell number and metabolic irregularities. CD169+ macrophages are a unique type of resident macrophages in the lymphoid organs that present cancer-derived antigens to CD8+ cells. The antigen-presenting role of CD169+ macrophages to T cells, a pivotal step in adaptive immunity, signifies the catastrophic implications of their suppression. This study underscores CD169+ macrophage suppression as a pronounced pathological phenotype in lymph nodes with breast cancer metastasis, thereby establishing it as a critical future therapeutic target. Citation Format: Yurina Maeshima, Tatsuki R. Kataoka, Alexis Vandenbon, Masahiro Hirata, Yasuhide Takeuchi, Yutaka Suzuki, Yukiko Fukui, Yumiko Ibi, Hironori Haga, Satoshi Morita, Masakazu Toi, Shinpei Kawaoka, Kosuke Kawaguchi. Selective elimination of CD169+ macrophages in lymph nodes invaded by breast cancers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-01.

Abstract 106: Selective elimination of CD169+ macrophages in lymph nodes invaded by breast cancers

Abstract Background: Lymph node metastasis is known as one of the strongest prognostic factors in breast cancer. The invasion mechanism of metastasized cancer cells in such immune cell-rich organs remains clear. Here, we aimed to elucidate the impact of metastasized cancer cells on the lymph node immune cell landscape. Methods: Multiscale transcriptomic analyses were performed on both metastatic and nonmetastatic lymph node samples from breast cancer patients with lymph node metastasis. As cancer cells interact with lymphocytes in lymph nodes in direct, proximal, and distant manners, we tried to capture the direct and proximal impact on immune cells in invaded lymph nodes by comparing paired metastatic and non-metastatic lymph node samples. Laser-micro-dissected sections were obtained from 17 lymph nodes across six breast cancer patients at stages II‒III, with each patient contributing both types of lymph nodes for direct comparison. We performed bulk transcriptome, spatial transcriptome, and imaging mass cytometry to analyze the obtained lymph nodes. Furthermore, we conducted immunohistochemistry analyses against a larger patient cohort (574 lymph nodes from 58 patients). Results: Comparing the transcriptomes of paired lymph nodes with and without metastasis from the same patients revealed selective downregulation of CD169+ macrophage-related genes in metastatic lymph nodes. The spatial transcriptome indicated a potential depletion of CD169+macrophages, initiators of anticancer immunity, from their residence in metastatic lymph nodes, while other principal immune cell types were unaltered. Mass cytometry imaging revealed that the numbers of CD169+ macrophages were smaller in the metastatic lymph nodes than in the nonmetastatic lymph nodes. Conversely, the number of B cells, CD4+ T cells, CD8+T cells, Treg cells, and CD11c+ cells remained comparable in both lymph node types. Additional immunohistochemistry analysis of 315 nonmetastatic lymph nodes and 159 metastatic lymph nodes from 58 patients with breast cancer showed that a reduced CD169+ macrophage population was prevalent in all breast cancer subtypes. CD169+ macrophages gradually decreased in correlation with pathological lymph node metastasis status, while no correlation was identified with pathological tumor size classification or metastasized cancer volume in invaded lymph nodes. Discussion: CD169+ macrophages are a unique type of resident macrophages in the lymphoid organs that present cancer-derived antigens to CD8+ T cells. The antigen-presenting role of CD169+ macrophages to T cells is a pivotal step in adaptive immunity. The elimination of CD169+ macrophage implies the disruption of the first step of the initial immune response. This study uncovered CD169+ macrophage suppression as a pronounced pathological phenotype in lymph nodes with breast cancer metastasis, thereby establishing it as a critical future therapeutic target. Citation Format: Yurina Maeshima, Tatsuki R. Kataoka, Alexis Vandenbon, Masahiro Hirata, Yasuhide Takeuchi, Yutaka Suzuki, Yukiko Fukui, Yumiko Ibi, Hironori Haga, Satoshi Morita, Masakazu Toi, Shinpei Kawaoka, Kosuke Kawaguchi. Selective elimination of CD169+ macrophages in lymph nodes invaded by breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 106.

Prediction of lymph node metastasis in advanced gastric adenocarcinoma based on dual-energy CT radiomics: focus on the features of lymph nodes with a short axis diameter ≥6 mm.

To explore the value of the features of lymph nodes (LNs) with a short-axis diameter ≥6 mm in predicting lymph node metastasis (LNM) in advanced gastric adenocarcinoma (GAC) based on dual-energy CT (DECT) radiomics. Data of patients with GAC who underwent radical gastrectomy and LN dissection were retrospectively analyzed. To ensure the correspondence between imaging and pathology, metastatic LNs were only selected from patients with pN3, nonmetastatic LNs were selected from patients with pN0, and the short-axis diameters of the enrolled LNs were all ≥6 mm. The traditional features of LNs were recorded, including short-axis diameter, long-axis diameter, long-to-short-axis ratio, position, shape, density, edge, and the degree of enhancement; univariate and multivariate logistic regression analyses were used to establish a clinical model. Radiomics features at the maximum level of LNs were extracted in venous phase equivalent 120 kV linear fusion images and iodine maps. Intraclass correlation coefficients and the Boruta algorithm were used to screen significant features, and random forest was used to build a radiomics model. To construct a combined model, we included the traditional features with statistical significance in univariate analysis and radiomics scores (Rad-score) in multivariate logistic regression analysis. Receiver operating curve (ROC) curves and the DeLong test were used to evaluate and compare the diagnostic performance of the models. Decision curve analysis (DCA) was used to evaluate the clinical benefits of the models. This study included 114 metastatic LNs from 36 pN3 cases and 65 nonmetastatic LNs from 28 pN0 cases. The samples were divided into a training set (n=125) and a validation set (n=54) at a ratio of 7:3. Long-axis diameter and LN shape were independent predictors of LNM and were used to establish the clinical model; 27 screened radiomics features were used to build the radiomics model. LN shape and Rad-score were independent predictors of LNM and were used to construct the combined model. Both the radiomics model (area under the curve [AUC] of 0.986 and 0.984) and the combined model (AUC of 0.970 and 0.977) outperformed the clinical model (AUC of 0.772 and 0.820) in predicting LNM in both the training and validation sets. DCA showed superior clinical benefits from radiomics and combined models. The models based on DECT LN radiomics features or combined traditional features have high diagnostic performance in determining the nature of each LN with a short-axis diameter of ≥6 mm in advanced GAC.

Dual-Energy CT Material Decomposition: The Value in the Detection of Lymph Node Metastasis from Breast Cancer.

To evaluate the diagnostic performance of a dual-energy computed tomography (DECT)-based material decomposition algorithm for iodine quantification and fat fraction analysis to detect lymph node metastases in breast cancer patients. 30 female patients (mean age, 63.12 ± 14.2 years) diagnosed with breast cancer who underwent pre-operative chest DECT were included. To establish a reference standard, the study correlated histologic repots after lymphadenectomy or confirming metastasis in previous/follow-up examinations. Iodine concentration and fat fraction were determined through region-of-interest measurements on venous DECT iodine maps. Receiver operating characteristic curve analysis was conducted to identify the optimal threshold for differentiating between metastatic and non-metastatic lymph nodes. A total of 168 lymph nodes were evaluated, divided into axillary (metastatic: 46, normal: 101) and intramammary (metastatic: 10, normal: 11). DECT-based fat fraction values exhibited significant differences between metastatic (9.56 ± 6.20%) and non-metastatic lymph nodes (41.52 ± 19.97%) (p < 0.0001). Absolute iodine concentrations showed no significant differences (2.25 ± 0.97 mg/mL vs. 2.08 ± 0.97 mg/mL) (p = 0.7999). The optimal fat fraction threshold for diagnosing metastatic lymph nodes was determined to be 17.75%, offering a sensitivity of 98% and a specificity of 94%. DECT fat fraction analysis emerges as a promising method for identifying metastatic lymph nodes, overcoming the morpho-volumetric limitations of conventional CT regarding lymph node assessment. This innovative approach holds potential for improving pre-operative lymph node evaluation in breast cancer patients, offering enhanced diagnostic accuracy.

Chemoradiotherapy and Lymph Node Metastasis Affect Dendritic Cell Infiltration and Maturation in Regional Lymph Nodes of Laryngeal Cancer.

Dendritic cells (DCs) are the most specialized antigen-presenting cells, and lymph nodes (LNs) play an important role in the DC-mediated T-cell response. We evaluated the infiltration of CD1a-positive DCs (CD1a-DCs), i.e., immature DCs, and S100-positive dendritic cells (S100-DCs), a mixture of immature and mature DCs, in 73 cases of laryngeal cancer and its regional LNs. Among them, 31 patients underwent radiotherapy (RT) or chemoradiotherapy (CRT) prior to surgery. No significant difference was found for CD1a-DC infiltration in the primary tumors, metastatic LNs and non-metastatic LNs, while S100-DCs were significantly fewer in number in the primary tumors and metastatic LNs compared to non-metastatic LNs. The cases which showed a high infiltration of S100-DCs in the metastatic LNs appeared to show a favorable prognosis, although statistical significance was not reached. In the RT/CRT group, the infiltration of the CD1a-DCs and S100-DCs was less in the primary tumors and metastatic LNs compared to the treatment-naive group. Conversely, the RT/CRT group showed higher CD1a-DC and S100-DC numbers in the non-metastatic LNs compared to the treatment-naïve group. Thus, DC maturation in metastatic LNs plays an important role in tumor immunity in laryngeal cancer, and the infiltration of DCs into the primary tumor and metastatic LNs is impaired by RT/CRT.