A Prospective Multicenter Study on the Additive Value of Contrast-Enhanced Ultrasound for Biopsy Decision of Ultrasound BI-RADS 4 Breast Lesions.

OBJECTIVE: The main aim of this study was to determine whether the use of contrast-enhanced ultrasound (CEUS) could improve the categorization of suspicious breast lesions based on the Breast Imaging Reporting and Data System (BI-RADS), thereby reducing the number of benign breast lesions referred for biopsy. METHODS: This prospective study, conducted between January 2017 and December 2018, enrolled consenting patients from eight teaching hospitals in China, who had been diagnosed with solid breast lesions classified as BI-RADS 4 using conventional ultrasound. CEUS was performed within 1 wk of diagnosis for reclassification of breast lesions. Histopathological results obtained from core needle biopsies or surgical excision samples served as the reference standard. The simulated biopsy rate and cancer-to-biopsy yield were used to compare the accuracy of CEUS and conventional ultrasound (US). RESULTS: Among the 1490 lesions diagnosed as BI-RADS 4 with conventional ultrasound, 486 malignant and 1004 benign lesions were confirmed based on histology. Following CEUS, 2, 395, and 211 lesions were reclassified as CEUS-based BI-RADS 2, 3, and 5, respectively, while 882 (59%) remained as BI-RADS 4. The actual cancer-to-biopsy yield based on US was 32.6%, which increased to 43.4% when CEUS-based BI-RADS 4A was used as the cut-off point to recommend biopsy. The simulated biopsy rate decreased to 73.4%. Overall, in this preselected BI-RADS 4 population, only 2.5% (12/486) of malignant lesions would have been miscategorized as BI-RADS 3 using CEUS-based reclassification. The diagnostic accuracy, sensitivity, and specificity of contrast-enhanced ultrasound reclassification were 57.65%, 97.53%, and 38.35%, respectively. CONCLUSION: Our collective findings indicate that CEUS is a valuable tool in further triage of BI-RADS category 4 lesions and facilitates a reduction in the number of biopsies while increasing the cancer-to-biopsy yield.

Influence of the initial recurrence site on prognosis after radical surgery for colorectal cancer: a retrospective cohort study.

BACKGROUND & AIMS: In this retrospective study, we aimed to elucidate how the initial recurrence site influences the post-recurrence survival (PRS) after the curative resection of colorectal cancer. PATIENTS AND METHODS: We collected samples from patients with stage I-III colorectal adenocarcinoma who were admitted to Yunnan Cancer Hospital from January 2008 to December 2019. Four hundred and six patients who developed recurrence after radical resection were included. The cases were classified according to the original site of recurrence as follows: liver metastases (n = 98), lung metastases (n = 127), peritoneum (n = 32), other individual organ (n = 69), two or more organs or sites (n = 49), and local recurrence (n = 31). Kaplan-Meier survival curves were used to compare the PRS of patients with different initial sites of recurrence. The influence of the initial recurrence site on PRS was analyzed using the Cox proportional hazards model. RESULTS: The 3-year PRS of simple liver metastasis was 54.04% (95% CI, 45.46%-64.24%), and the 3-year PRS of simple lung metastasis was 50.05% (95% CI, 42.50%-58.95%). No significant difference was observed between simple liver metastasis or simple lung metastasis and local recurrence with a 3-year PRS of 66.99% (95% CI, 53.23%-84.32%). The 3-year PRS for peritoneal metastases was 25.43% (95% CI, 14.76%-43.82%), and the 3-year PRS for two or more organ sites was 34.84% (95% CI, 24.16%-50.24%). The peritoneal (hazard ratio [HR], 1.75; 95% CI, 1.10-2.79; P = 0.0189) and metastasis to two or more organs or sites (HR, 1.59; 95% CI, 1.05-2.43; P = 0.0304) were PRS-independent adverse prognostic factors. CONCLUSION: The prognosis of patients with peritoneum and multiple organs or sites recurred was poor. This study suggests early monitoring of peritoneal and multiple organ or site recurrence after surgery. This part of patients should receive comprehensive treatment as early as possible to improve their prognosis.

Pregnancy-associated plasma protein-A (PAPPA) promotes breast cancer progression.

Breast cancer is the most common malignancy in females and poses a significant health threat to women. Pregnancy-associated plasma protein-A (PAPPA) is highly expressed in pregnancy-associated breast cancer (PABC) tissues. In this study, we investigated the functional role of PAPPA in regulating the malignant phenotype of breast cancer. We first examined the expression level of PAPPA in PABC tissue and breast cancer cell lines using quantitative real-time polymerase-chain reaction (qRT-PCR) and western blot. Next, the functional role of PAPPA in breast cancer cells was validated by overexpression and knockdown experiments. Cell counting kit-8 (CCK-8) proliferation assay, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, wound healing and transwell invasion assay were used to examine cell proliferation, migration, and invasion ability. We further identified the microRNA target regulating PAPPA and studied its functional role. Finally, we examined the impact of PAPPA on the tumorigenesis and metastasis of breast cancer in mice model. Our study revealed that PAPPA was upregulated in PABC tissues and breast cancer cells. Overexpression of PAPPA promoted cell proliferation, motility, invasion, and epithelial-mesenchymal transition (EMT). We further identified miR-497-5p as a negative regulator of PAPPA, which suppressed cell proliferation, migration, invasion, and EMT in breast cancer cells. We also validated the oncogenic role of PAPPA in the mouse xenograft model. Collectively, our study suggests that PAPPA is an oncogenic protein highly expressed in PABC tissues and promotes breast cancer progression, which could serve as a novel therapeutic target for breast cancer.

Knockdown of circ_NEK6 Decreased 131I Resistance of Differentiated Thyroid Carcinoma via Regulating miR-370-3p/MYH9 Axis.

Radioresistance is a crucial factor for the failure of iodine 131 (131I)-based radiotherapy for differentiated thyroid carcinoma (DTC). This study aimed to explore the effect of circ_NEK6 on the development of 131I resistance in DTC and its potential mechanism. In this study, we demonstrated that circ_NEK6 expression was significantly elevated in 131I-resistant DTC tissues and cell lines. Knockdown of circ_NEK6 significantly repressed 131I resistance via inhibiting cell proliferation, migration, invasion abilities, and inducing cell apoptosis and DNA damage in 131I-resistant DTC cells. Mechanistically, knockdown of circ_NEK6 suppressed 131I resistance in DTC by upregulating the inhibitory effect of miR-370-3p on the expression of myosin heavy chain 9 (MYH9). In vivo experiments showed that circ_NEK6 inhibition aggravated 131I radiation-induced inhibition of xenograft tumor growth. Taken together, knockdown of circ_NEK6 repressed 131I resistance in DTC cells by regulating the miR-370-3p/MYH9 axis, indicating that circ_NEK6 may act as a potential biomarker and therapeutic target for DTC patients with 131I resistance.

A multicenter study of a contrast-enhanced ultrasound diagnostic classification of breast lesions.

PURPOSE: To evaluate a classification model of contrast-enhanced ultrasound (CEUS) and examine the characteristics of patients with false-negative diagnosis. PATIENTS AND METHODS: A retrospective secondary analysis of a multicenter trial of CEUS for breast cancer diagnosis (from August 2015 to April 2017) was undertaken. Patients (n=1,023) with Breast Imaging Reporting and Data System 4-5 lesions on B-mode ultrasound underwent CEUS. Pathological diagnoses were available from surgical or biopsy specimens for correlation. Lesion maximum diameter (LMD), distance to the papilla (DtP), distance from the superficial edge of the lesion to the skin (DtS), distance from the deep edge of the lesion to the pectoralis muscle (DtPM), and body mass index (BMI) were evaluated. RESULTS: Median age and BMI were 48.0 and 41.2 years and 23.2 and 22.4 kg/m2 for patients with malignant and benign lesions, respectively. Overall sensitivity, specificity, and accuracy of CEUS for malignancy were 89.4%, 65.3%, and 75.8%, respectively. The patients with true-positive and false-negative diagnosis (ie, with malignant lesion) were older than those with false-positive and true-negative diagnosis (ie, with benign lesion). Patients with true-positive and false-positive diagnoses had higher BMI than patients with true-negative and false-negative diagnoses (P=0.004). Patients with true-positive and false-negative diagnoses had larger LMD and DtP, as well as smaller DtS and DtPM. CONCLUSION: Older age, higher BMI, larger LMD and DtP, and smaller DtS and DtPM were associated with malignant lesions on CEUS. Patients with these characteristics should undergo further imaging.

Factors influencing the performance of a diagnostic model including contrast-enhanced ultrasound in 1023 breast lesions: comparison with histopathology.

BACKGROUND: We aimed to investigate the influence of patient and lesion characteristics on our diagnostic model for contrast-enhanced ultrasound (CEUS) of the breast, comparing its accuracy with that of histopathology. METHODS: Conducting a study with eight medical centers, we compared 1,023 breast lesions categorized as BI-RADS 4 or 5 with the score from our newly-established CEUS-based diagnostic model, comparing the results with pathological outcomes. Univariate and multivariate logistic regression analyses were conducted to determine the influence of clinicopathological characteristics on the performance of this CEUS model. RESULTS: Logistic regression analysis showed that patients' age, maximum lesion diameter, and distance from the lesion's deep edge to the pectoralis major were significant independent influencing factors. The model's diagnostic accuracy was greater for patients >35 y (P=0.005), for maximum lesion diameter >20 mm, and for distance from the lesion's deep edge to the pectoralis major ≤3.05 mm. There was no significant difference in accuracy between lesions with maximum lesion diameter 10-20 and <10 mm (P=0.393). CONCLUSIONS: The diagnostic performance of the proposed CEUS model for breast lesions is influenced by patients' age, maximum lesion diameter, and distance from the lesion's deep edge to the pectoralis major. Consideration of influencing factors is required to optimize clinical use of the CEUS model.