Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis.

Breast cancer (BC) is the most prevalent cancer in women. While usually detected when localized, invasive procedures are still required for diagnosis. Herein, we developed a novel ultrasensitive pipeline to detect circulating tumor DNA (ctDNA) in a series of 75 plasma samples from localized BC patients prior to any medical intervention. We first performed a tumor-informed analysis to correlate the mutations found in tumor tissue and plasma. Disregarding the tumor data next, we developed an approach to detect tumor mutations in plasma. We observed a mutation concordance between the tumor and plasma of 29.50% with a sensitivity down to 0.03% in mutant variant allele frequency (VAF). We detected mutations in 33.78% of the samples, identifying eight patients with plasma-only mutations. Altogether, we determined a specificity of 86.36% and a positive predictive value of 88.46% for BC detection. We demonstrated an association between higher ctDNA median VAF and higher tumor grade, multiple plasma mutations with a likelihood of relapse and more frequent TP53 plasma mutations in hormone receptor-negative tumors. Overall, we have developed a unique ultra-sensitive sequencing workflow with a technology not previously employed in early BC, paving the way for its application in BC screening.

[Renal pseudoaneurysm and arteriovenous fistula: color doppler study of a post-lithotripsy simple cyst]. / Pseudoaneurisma y fístula arteriovenosa renal estudio mediante doppler color de quiste simple post-litotricia.

OBJECTIVES: To describe the clinical and radiological (color doppler ultrasound, CT scan and arteriography) features of a case of renal arteriovenous malformation type mixed fistula with pseudoaneurysm in a female patient after extracorporeal shock wave lithotripsy. METHODS/RESULTS: We report one case of secondary vascular malformation in a 54-year-old female patient who underwent extracorporeal shockwave lithotripsy, presenting as recurrent hematuria. Ultrasound detected a "cystic" formation newly appeared after lithotripsy, being the diagnostic made by a color doppler study which showed a mixed high speed arteriovenous turbulent flow. The lesion showed intense intravenous contrast uptake on CT scan. Diagnosis was confirmed by arteriography. CONCLUSIONS: External shock wave lithotripsy is, as well as interventional procedures, a known cause of renal vascular complications, so that doppler color studies may be diagnostic in patients with suggestive clinical features, focusing specially on those lesions or morphological abnormalities newly appeared when compared to pre-treatment studies.