Summary of Meta-analyses of Studies Considering Lesion Size Cut-off Thresholds for The Assessment of Eligibility for FNAB and Sonoelastography and Inter- and Intra-observer Agreement in Estimating the Malignant Potential of Focal Lesions of The Thyroid Gland.

Thyroid cancer is a tumour with a steadily increasing incidence. It accounts for 7% to 15% of focal lesions detected by ultrasound, depending on age, gender and other factors affecting its occurrence. Fine-needle aspiration biopsy is an essential method to establish the diagnosis but, in view of its limitations, sonoelastography is seen as a non-invasive technique useful in differentiating the nature of lesions and monitoring them after fine-needle aspiration biopsy. This paper presents a literature review on the role of both sonoelastographic techniques (relative strain sonoelastography, shear wave sonoelastography) to assess the deformability of focal thyroid lesions. Ultrasound examination is a relatively subjective method of thyroid imaging, depending on the skills of the examiner, the experience of the centre, and the quality of equipment used. As a consequence, there are inconsistencies between the results obtained by different examiners (inter-observer variability) and by the same examiner (intra-observer variability). In this paper, the authors present a review of the literature on inter-observer and intra-observer variability in the assessment of individual features of ultrasound imaging of focal lesions in the thyroid. In addition, the authors report on an analysis of cut-off thresholds for the size of lesions constituting the basis for fine-needle aspiration biopsy eligibility assessment. The need to diagnose carcinomas up to 10 mm in diameter is highlighted, however a more liberal approach is recommended in terms of indications for biopsy in lesions associated with a low risk of malignancy, where, based on consultations with patients, active ultrasound surveillance might even be considered.

Assessment of breast cancer response to neoadjuvant chemotherapy based on ultrasound backscattering envelope statistics.

PURPOSE: Neo-adjuvant chemotherapy (NAC) is used in breast cancer before tumor surgery to reduce the size of the tumor and the risk of spreading. Monitoring the effects of NAC is important because in a number of cases the response to therapy is poor and requires a change in treatment. A new method that uses quantitative ultrasound to assess tumor response to NAC has been presented. The aim was to detect NAC unresponsive tumors at an early stage of treatment. METHODS: The method assumes that ultrasound scattering is different for responsive and nonresponsive tumors. The assessment of the NAC effects was based on the differences between the histograms of the ultrasound echo amplitude recorded from the tumor after each NAC dose and from the tissue phantom, estimated using the Kolmogorov-Smirnov statistics (KSS) and the symmetrical Kullback-Leibler divergence (KLD). After therapy, tumors were resected and histopathologically evaluated. The percentage of residual malignant cells was determined and was the basis for assessing the tumor response. The data set included ultrasound data obtained from 37 tumors. The performance of the methods was assessed by means of the area under the receiver operating characteristic curve (AUC). RESULTS: For responding tumors, a decrease in the mean KLD and KSS values was observed after subsequent doses of NAC. In nonresponding tumors, the KLD was higher and did not change in subsequent NAC courses. Classification based on the KSS or KLD parameters allowed to detect tumors not responding to NAC after the first dose of the drug, with AUC equal 0.83 ± $\pm$ 0.06 and 0.84 ± $\pm$ 0.07, respectively. After the third dose, the AUC increased to 0.90 ± $\pm$ 0.05 and 0.91 ± $\pm$ 0.04, respectively. CONCLUSIONS: The results indicate the potential usefulness of the proposed parameters in assessing the effectiveness of the NAC and early detection of nonresponding cases.

Is There a Correlation between Multiparametric Assessment in Ultrasound and Intrinsic Subtype of Breast Cancer?

Molecular profile of breast cancer provides information about its biological activity, prognosis and treatment strategies. The purpose of our study was to investigate the correlation between ultrasound features and molecular subtypes of breast cancer. From June 2019 to December 2019, 86 patients (median age 57 years; range 32-88) with 102 breast cancer tumors were included in the study. The molecular subtypes were classified into five types: luminal A (LA), luminal B without HER2 overexpression (LB HER2-), luminal B with HER2 overexpression (LB HER2+), human epidermal growth factor receptor 2 positive (HER2+) and triple negative breast cancer (TNBC). Histopathological verification was obtained in core biopsy or/and post-surgery specimens in all cases. Univariate logistic regression analysis was performed to assess the association between the subtypes and ultrasound imaging features. Experienced radiologists assessed lesions according to the BIRADS-US lexicon. The ultrasound scans were performed with a Supersonic Aixplorer and Supersonix. Based on histopathological verification, the rates of LA, LB HER2-, LB HER2+, HER2+, and TNBC were 33, 17, 17, 16, 19, respectively. Both LB HER2+ and HER2+ subtypes presented higher incidence of calcification (OR = 3.125, p = 0.02, CI 0.0917-5.87) and HER2+ subtype presented a higher incidence of posterior enhancement (OR = 5.75, p = 0.03, CI 1.2257-32.8005), compared to other subtypes. The calcifications were less common in TNBC (OR = 0.176, p = 0.0041, CI 0.0469-0.5335) compared to other subtypes. There were no differences with regard to margin, shape, orientation, elasticity values and vascularity among five molecular subtypes. Our results suggest that there is a correlation between ultrasonographic features assessed according to BIRADS-US lexicon and BC subtypes with HER2 overexpression (both LB HER2+ and HER2+). It may be useful for identification of these aggressive subtypes of breast cancer.

Quantitative Assessment of the Echogenicity of a Breast Tumor Predicts the Response to Neoadjuvant Chemotherapy.

The aim of the study was to improve monitoring the treatment response in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The IRB approved this prospective study. Ultrasound examinations were performed prior to treatment and 7 days after four consecutive NAC cycles. Residual malignant cell (RMC) measurement at surgery was the standard of reference. Alteration in B-mode ultrasound (tumor echogenicity and volume) and the Kullback-Leibler divergence (kld), as a quantitative measure of amplitude difference, were used. Correlations of these parameters with RMC were assessed and Receiver Operating Characteristic curve (ROC) analysis was performed. Thirty-nine patients (mean age 57 y.) with 50 tumors were included. There was a significant correlation between RMC and changes in quantitative parameters (KLD) after the second, third and fourth course of NAC, and alteration in echogenicity after the third and fourth course. Multivariate analysis of the echogenicity and KLD after the third NAC course revealed a sensitivity of 91%, specificity of 92%, PPV = 77%, NPV = 97%, accuracy = 91%, and AUC of 0.92 for non-responding tumors (RMC ≥ 70%). In conclusion, monitoring the echogenicity and KLD parameters made it possible to accurately predict the treatment response from the second course of NAC.

Assessment of Anti-Tumor potential and safety of application of Glutathione stabilized Gold Nanoparticles conjugated with Chemotherapeutics.

Due to the high toxicity of currently used chemotherapeutics, novel methods of cancer treatment are needed. Gold nanoparticles (AuNPs) seem to be an interesting alternative due to penetration through biological membranes and systemic barriers. AuNPs as carriers of chemotherapeutics allow for reduced concentrations whilst maintaining the expected effect, and thus reducing the costs of therapy and adverse effects. We synthesized AuNPs stabilized with reduced glutathione (GSH) and conjugated with doxorubicin (DOX), gemcitabine (GEM) or cytarabine (CTA). This is the first study in which cytarabine-AuNPs were synthesized and characterized. Transmission electron microscopy (TEM), thermogravimetric analysis (TGA), nuclear magnetic resonance spectroscopy (NMR) and high-performance liquid chromatography (HPLC) were used to chemically characterize obtained nanoparticles. Antitumor activity and safety of application were assessed by MTT assay in in vitro model (human osteosarcoma cells -143B, human osteoblast- hFOB1.19, breast cancer cells - MCF7, breast epithelial cells - MCF10A, pancreatic cancer cells - PANC-1, and pancreatic cells - hTERT-HPNE cells). We have shown that cellular response varies according to the type and concentration of AuNPs. At some concentrations, we were able to show selective cytotoxicity of our AuNPs conjugates only to cancer cell lines. Synthesized nanoparticles were more cytotoxic to tumor cell lines than chemotherapeutics alone.

Prospective analysis of inter-observer and intra-observer variability in multi ultrasound descriptor assessment of thyroid nodules.

Aim: The aim of this study was to evaluate the inter- and intra-observer variability and accuracy of ultrasound assessment of thyroid nodules using a descriptive lexicon. Materials and methods: A prospective study was performed on complete ultrasound examinations, including sonoelastography and color Doppler ultrasound of 18 patients with 20 thyroid nodules. A total of 20 records of thyroid nodules from these techniques were duplicated, numbered, and randomly arranged. Five radiologists assessed the recordings independently. Cohen Kappa and Fleiss Kappa statistics were used to determine the degree of intra- and inter-observer agreement. Results: Mean accuracy rates for all radiologists, for all ultrasound features, ranged from 82.7 to 87.8%. For B-mode and strain elastography, accuracies ranged from 65.0 to 100% and 47.4 to 86.8%, respectively. Concerning intra-observer variability, three radiologists demonstrated almost perfect agreement (the κ-value ranged from 0.81 to 0.86), and a substantial agreement was noted for the two remaining radiologists. The κ-values for inter-observer agreement ranged from 0.61 for macrocalcifications (substantial agreement) to 0.33 for Asteria four-point elastography scale criteria (fair agreement). Conclusions: The results suggest relatively good inter-observer and excellent intra-observer agreement in the assessment of thyroid nodules using ultrasound, and fair agreement in the case of strain elastography.

Fine-needle versus core-needle biopsy - which one to choose in preoperative assessment of focal lesions in the breasts? Literature review.

AIM: The aim of the study was to review two techniques that can be used to verify focal lesions in the breasts: fine-needle aspiration biopsy and core-needle biopsy. MATERIAL AND METHODS: Fifty-five articles (original papers and reviews), half of them published within the past 5 years, were included in the analysis. The authors also took their own experience into account. RESULTS: Pre-operative assessment of focal lesions in the breasts is crucial in the planning of further therapeutic management. The role of fine-needle aspiration biopsy has been reduced lately due to its low sensitivity and specificity as well as a high rate of non-diagnostic, suspicious and false negative results. This method does not enable one to differentiate between in situ and invasive disease. Currently, fine-needle biopsy is recommended for cystic lesions, suspected of being recurrences in the chest wall, and lymph node metastases. Core-needle biopsy is the basic diagnostic method of breast lesions. According to the recommendations of the Polish Ultrasound Society and American College of Radiology, BIRADS 4 and 5 lesions should be evaluated histopathologically. Core-needle biopsy makes it possible to establish a final diagnosis more frequently than fine-needle biopsy, both in the case of benign and malignant lesions. It delivers more information about the nature of a tumor (mutation of HER-2, estrogen and progesterone receptors and Ki-67 index). Its limitations include: underestimation of invasion and failure to recognize the components of ductal carcinoma in situ in papillary and atypical lesions. Single fine-needle aspiration biopsy is inexpensive, but when considering the cost of further diagnosis due to non-diagnostic, suspicious and atypical results, this method generates high additional costs. CONCLUSIONS: Microscopic verification of focal breast lesions is crucial for further therapeutic decisions. It has been proven that histopathological verification is more accurate and has more advantages than cytological assessment.

The role of ultrasound and lymphoscintigraphy in the assessment of axillary lymph nodes in patients with breast cancer.

Breast cancer is the most common malignancy and the leading cause of death due to cancer in European women. Mammography screening programs aimed to increase the detection of early cancer stages were implemented in numerous European countries. Recent data show a decrease in mortality due to breast cancer in many countries, particularly among young women. At the same time, the number of sentinel node biopsy procedures and breast-conserving surgeries has increased. Intraoperative sentinel lymph node biopsy preceded by lymphoscintigraphy is used in breast cancer patients with no clinical signs of lymph node metastasis. Due to the limited sensitivity and specificity of physical examination in detecting metastatic lesions, developing an appropriate diagnostic algorithm for the preoperative assessment of axillary lymph nodes seems to be a challenge. The importance of ultrasound in patient qualification for sentinel lymph-node biopsy has been discussed in a number of works. Furthermore, different lymphoscintigraphy protocols have been compared in the literature. The usefulness of novel radiopharmaceuticals as well as the methods of image acquisition in sentinel lymph node diagnostics have also been assessed. The aim of this article is to present, basing on current guidelines, literature data as well as our own experience, the diagnostic possibilities of axillary lymph node ultrasound in patient qualification for an appropriate treatment as well as the role of lymphoscintigraphy in sentinel lymph node biopsy.