Establishment of a logistic regression model nomogram for clinicopathological characteristics and risk factors with axillary lymph node metastasis in T1 locally advanced breast cancer: a retrospective study.

Background: Although the research reports on locally advanced breast cancer (LABC) are increasing year by year, there are few reports on T1 LABC axillary lymph node metastasis (ALNM). By establishing a prediction model for T1 LABC ALNM, this study provides a reference value for the probability of ALNM of related patients, which helps clinicians to develop a more effective and individualized treatment plan for LABC. Methods: Cases with pathologically confirmed T1 breast cancer (BC) between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were identified. Logistic regression was used to analyze the correlation between LABC lymph node metastasis and every factor, and the odds ratio (OR) and 95% confidence interval (CI) were used to identify any influencing factors. A nomogram was drawn after incorporating meaningful factors identified in multivariate logistic regression into the model. The receiver operating characteristic (ROC) curve of the model was drawn, and the area under the curve (AUC) and its 95% CI were calculated. Hosmer-Lemeshow goodness-of-fit test and clinical decision curve analysis (DCA) were performed. The results were validated in the validation group. Results: A total of 200,933 female T1 BC patients were included in this study. Univariate and multivariate logistic regression analysis of T1 BC showed that progesterone receptor (PR)-negative, race, age, lobular carcinoma, micropapillary ductal carcinoma, axillary tail tumor, poor differentiation, and larger tumor diameter increased the probability of ALNM in T1 LABC. A predictive nomogram was established using the above predictors, the AUC of the modeling group was 0.739 (95% CI: 0.732-0.747), and when the AUC cut-off value was 0.026, the specificity and sensitivity of the model were 65.78% and 69.99%, respectively. Validation of the model showed that the AUC of the validation group (n=60,280) was 0.741. When all the risk factors were met, the predicted probability of N2-N3 was 50.40%. Conclusions: In this study, it was found that PR-negative, Black race, age, lobular carcinoma, micropapillary ductal carcinoma, axillary tail tumor, poor differentiation, and tumor diameter increased the probability of large lymph node metastasis in T1 LABC small tumors.

The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients.

This meta-analysis aimed to evaluate the diagnostic accuracy of touch imprint cytology (TIC) for sentinel lymph node (SLN) metastases of patients with clinical node-negative early breast cancer. The PubMed, Web of Science, Embase, and the Cochrane Library databases were meticulously searched to retrieve literature published from January 2005 to September 2022 by two independent reviewers. The meta-analysis was performed using STATA16.0, Meta-Disc 1.4, and RevMan 5.4.9. According to the inclusion criteria, 4,073 patients from 13 studies were included in this meta-analysis. The pooled sensitivity and specificity of TIC for detecting SLN metastases were 0.77 (95% CI 0.66-0.85) and 0.99 (95% CI 0.97-1.00), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 76.15 (95% CI 29.16-198.84) and 0.23 (95% CI 0.15-0.36), respectively. The pooled diagnostic odds ratio was 326.82 (95% CI 132.76-804.56) and the area under the sROC curve was 0.97 (95% CI 0.95-0.98), respectively. This meta-analysis revealed that TIC with high sensitivity and specificity is a feasibility and accuracy diagnosis technique for intraoperative detection of SLN metastases in breast cancer.

Noninvasive PET Imaging of a Ga-68-Radiolabeled RRL-Derived Peptide in Hepatocarcinoma Murine Models.

PURPOSE: Tc-99m- and I-131-labeled arginine-arginine-leucine (RRL) peptides have shown the feasibility of tumor imaging in our previous studies. However, there have been no reports using RRL peptide for positron emission tomography (PET) imaging. In this study, RRL was radiolabeled with Ga-68 under optimized reaction conditions to develop a better specific and effective tumor imaging agent. PROCEDURES: RRL was synthesized and conjugated to a bifunctional chelating agent (DOTA-NHS), then radiolabeled with Ga-68. Labeling yield was optimized by varying pH, temperature, and reaction time and the stability was evaluated in human fresh serum. Cellular uptakes of [68Ga]DOTA-RRL and FITC-conjugated RRL in HepG2 cells were evaluated using a gamma counter, confocal microscopy, and flow cytometry. PET images and biodistribution were performed in HepG2 tumor-bearing mice after injection of [68Ga]DOTA-RRL or [68Ga]GaCl3 at different time points. Further, blocking study was investigated using cold RRL. RESULTS: The labeling yield of [68Ga]DOTA-RRL was 80.6 ± 3.9 % with a pH of 3.5-4.5 at 100 °C for 15 min. The cellular uptake of [68Ga]DOTA-RRL in HepG2 cells was significantly higher than that of [68Ga]GaCl3 (P < 0.05). Moreover, the high fluorescent affinity of FITC-conjugated RRL in HepG2 cells was shown using confocal microscopy and flow cytometry. After injection of [68Ga]DOTA-RRL in HepG2 tumor-bearing mice, tumor regions exhibited high radioactive accumulation over 120 min and the highest uptake at 30 min. After blocked with cold RRL, HepG2 tumors could not be visualized. [68Ga]GaCl3 was unable to show tumor images at any time point. The biodistribution results confirmed the PET imaging and blocking results. CONCLUSIONS: Our study successfully prepared [68Ga]DOTA-RRL with a high labeling yield under the optimized reaction conditions and demonstrated its potential role as a PET imaging agent for tumor-targeted diagnosis.

Significant Association of CXCL12 rs1746048 with LDL-C Level in Intracranial Aneurysms.

BACKGROUND: C-X-C motif chemokine ligand 12 (CXCL12) may play an important role in the development of Intracranial Aneurysm (IA). OBJECTIVE: The goal of this study was to explore the association between CXCL12 rs1746048 genotypes and circulating lipid concentrations along with the risk of IA. METHODS: A total of 256 IA patients and 361 healthy volunteers were included in the case-control study. The genotypes of CXCL12 rs1746048 were detected by Melting Temperature shift (Tmshift) Polymerase Chain Reaction (PCR). RESULTS: Significant higher levels were seen in Total Cholesterol (TC) (padjusted < 0.001), Highdensity Lipoprotein Cholesterol (HDL-C) (padjusted < 0.001), Low-density Lipoprotein Cholesterol (LDL-C) (padjusted < 0.001), Apolipoprotein A-I (ApoA-I) (padjusted = 0.040), and Apolipoprotein B (ApoB) (padjusted < 0.001) in IAs compared with controls. CXCL12 rs1746048 T allele frequency showed significant association with the risk of IA in the female group aged 65 or above (p = 0.019, Odds Ratio (OR) = 2.15, 95% confidence interval (95%CI) = 1.13 - 4.11, power = 64.8%). Moreover, CXCL12 rs1746048 was likely to be a risk variant of IA under the recessive model in females older than 65 years. (p = 0.030, OR = 3.77, 95%CI = 1.08 - 13.12, power = 81.8%). Additionally, we also found that the levels of LDL-C were significantly different among three genotypes (CC vs. CT vs. TT = 2.75±0.73 vs. 3.03±0.89 vs. 2.82±0.72, p = 0.035) in IA patients. CONCLUSION: Our results suggest that CXCL12 rs1746048 is significantly associated with IA risk in Han Chinese females aged 65 years and older. Additionally, the genotypes of CXCL12 rs1746048 may affect the LDL-C concentrations in IA patients.