Dataset Information

Detection of Lymph Node Metastases by Ultra-pH-Sensitive Polymeric Nanoparticles.

ABSTRACT: Lymph node (LN) dissection followed by histological analysis is the current standard for diagnosis of LN metastasis but the method suffers from patient morbidity and low sensitivity of detection. Ultra-pH sensitive (UPS) nanoparticles show remarkable accuracy in the delineation of primary tumor margins for precision cancer surgery. Herein we investigate the effectiveness of UPS nanoparticles to detect cancer-involved LNs. Methods: We synthesized a series of indocyanine green (ICG) conjugated UPS nanoparticles with distinct pKa (UPS5.3, UPS6.1, and UPS6.9). Systemically administered UPS-ICG nanoparticles in the 4T1.2-BALB/cj mouse model were imaged with real-time, near-infrared fluorescence (NIRF) to guide removal of LNs. Ex vivo imaging of gross tissue enabled quantification of fluorescence intensity. Histological analysis was used as the gold standard diagnostic test. Results: Macrophage uptake of UPS nanoparticles elevates the background signal in benign LNs. However, cancer foci within LNs show distinctive clustering of UPS-ICG fluorescence. UPS5.3 achieves accurate detection of metastatic LNs as shown by a receiver operating characteristic (ROC) area under the curve (AUC) of 0.96 ± 0.03. UPS6.1 and UPS6.9 offer decreased discriminatory power at ROC AUC of 0.73 ± 0.1 and 0.88 ± 0.07, respectively. Conclusions: All UPS compositions show cancer-specific discrimination of metastatic LNs over benign LNs with the best outcomes from UPS5.3. Detection of micro-metastatic LNs (cancer foci < 2 mm) remains a challenge. This study provides information on the detection of LN status for image-guided resection of metastatic LNs.

SUBMITTER: Bennett ZT

PROVIDER: S-EPMC7053196 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Detection of Lymph Node Metastases by Ultra-pH-Sensitive Polymeric Nanoparticles.

Bennett Zachary T ZT Feng Qiang Q Bishop Justin A JA Huang Gang G Sumer Baran D BD Gao Jinming J

Theranostics 20200210 7

Lymph node (LN) dissection followed by histological analysis is the current standard for diagnosis of LN metastasis but the method suffers from patient morbidity and low sensitivity of detection. Ultra-pH sensitive (UPS) nanoparticles show remarkable accuracy in the delineation of primary tumor margins for precision cancer surgery. Herein we investigate the effectiveness of UPS nanoparticles to detect cancer-involved LNs. <b>Methods</b>: We synthesized a series of indocyanine green (ICG) conjuga ...[more]

PMID: 32194872

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Project description:BackgroundPatients with breast cancer presenting with single lymph node metastasis (from a sentinel node) experience prolonged survival compared to patients with multiple lymph node metastases (≥3). However, little information is available on the genetic and immunological characteristics of breast cancer metastases within the regional lymph nodes as they progress from the sentinel lymph node (SLN) downstream to multiple regional lymph nodes (MLNs).MethodsGenomic profiling was performed using a next-generation sequencing panel covering 520 cancer-related genes in the primary tumour and metastatic lymph nodes of 157 female patients with breast cancer. We included primary tumours, metastatic lymph nodes and adjacent clinically normal lymph nodes (20 patients from the SLN group and 28 patients from the MLNs group) in the whole transcriptome analysis.FindingsThe downstream metastatic lymph nodes (P = 0.029) and the primary breast tumours (P = 0.011) had a higher frequency of PIK3CA mutations compared to the SLN metastasis. We identified a distinct group of 14 mutations from single sentinel node metastasis and a different group of 15 mutations from multiple nodal metastases. Only 4 distinct mutations (PIK3CA, CDK4, NFKBIA and CDKN1B) were conserved in metastases from both lymph node settings. The tumour mutational burden (TMB) was significantly lower in single nodal metastasis compared to the paired primary breast cancer (P = 0.0021), while the decline in TMB did not reach statistical significance in the MLNs group (P = 0.083). In the gene set enrichment analysis, we identified 4 upregulated signatures in both primary tumour and nodal metastases from the MLNs group, including 3 Epithelial-mesenchymal transition(EMT) signatures and 1 angiogenesis signature. Both the CD8/Treg ratio and the CD8/EMT ratio were significantly higher in adjacent normal lymph nodes from patients with a single metastasis in the SLN compared with samples from the MLNs group (P = 0.045 and P = 0.023, respectively). This suggests that the immune defence from the MLNs patients might have a less favourable microenvironment, thus permitting multiple lymph nodes metastasis.InterpretationSingle lymph node metastases and multiple lymph node metastases have significant differences in their molecular profiles and immune profiles. The findings are associated with more aggressive tumour characteristics and less favourable immune charactoristics in patients with multiple nodal metastases compared to those with a single metastasis in the sentinel node.FundingThis work was supported by funds from High-level Hospital Construction Project (DFJH201921), the National Natural Science Foundation of China (81902828 and 82002928), the Fundamental Research Funds for the Central Universities (y2syD2192230), and the Medical Scientific Research Foundation of Guangdong Province (B2019039).

Project description:BackgroundUnlike medullary thyroid carcinoma in adults, the vast majority of pediatric medullary thyroid carcinoma is hereditary. Pediatric medullary thyroid carcinoma is known to have different genetic alterations driving tumorigenesis, but it is not known if pediatric medullary thyroid carcinoma has different clinicopathologic features. This study aims to identify which pediatric medullary thyroid carcinoma patients might warrant elective neck dissection.MethodsWe selected all patients ages 0 to 19 diagnosed with clinically evident medullary thyroid carcinoma in the National Cancer Database between 2004 to 2016. Clinicopathologic factors, treatments, and outcomes were analyzed and compared between this cohort and adults (ages ≥20) with medullary thyroid carcinoma.ResultsOne hundred twenty-five pediatric medullary thyroid carcinoma (median age: 13) and 5,086 adult medullary thyroid carcinoma (median age: 57) patients were identified. Pediatric patients had smaller tumors (median diameter: 1.2 cm vs 2.0 cm; P < .001), lower rates of nodal metastases (n = 31, 36.9% vs 1,689, 50.4%; P = .02) but double the incidence of multifocal tumors (n = 70, 59.3%, vs 1,412, 29.9%; P < .001) compared with adults. Multifocal tumors conferred a significantly increased risk of nodal metastases in adult medullary thyroid carcinoma (64.4% vs 43.2%; P < .001) but not pediatric medullary thyroid carcinoma (37.7% vs 35.7%; P = .85). Nodal metastases were more frequent among older children (0-5 years: 0.0%, 6-12: 40.7%, 13-19: 41.7%; P = .04). However, rates of occult nodal metastases were similar between older children (6-19 years: n = 12, 21.4%) and adults (557, 25.8% P = .56).ConclusionPediatric medullary thyroid carcinoma has lower rates of lymph node metastases compared with adults. The risk of nodal disease was low among the youngest children, but older children ages 6 to 19 were at considerable risk for occult metastases. These findings could guide clinicians in selecting pediatric patients considered for elective lymph node dissection.

Dataset Information

Detection of Lymph Node Metastases by Ultra-pH-Sensitive Polymeric Nanoparticles.

Publications

Detection of Lymph Node Metastases by Ultra-pH-Sensitive Polymeric Nanoparticles.

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