Tumor cell-based liquid biopsy using high-throughput microfluidic enrichment of entire leukapheresis product.

Circulating Tumor Cells (CTCs), interrogated by sampling blood from patients with cancer, contain multiple analytes, including intact RNA, high molecular weight DNA, proteins, and metabolic markers. However, the clinical utility of tumor cell-based liquid biopsy has been limited since CTCs are very rare, and current technologies cannot process the blood volumes required to isolate a sufficient number of tumor cells for in-depth assays. We previously described a high-throughput microfluidic prototype utilizing high-flow channels and amplification of cell sorting forces through magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.83 liters from patients with metastatic cancer, with a median of 2,799 CTCs purified per patient. Isolation of many CTCs from individual patients enables characterization of their morphological and molecular heterogeneity, including cell and nuclear size and RNA expression. It also allows robust detection of gene copy number variation, a definitive cancer marker with potential diagnostic applications. High-volume microfluidic enrichment of CTCs constitutes a new dimension in liquid biopsies.

Contact surface area and its association with outcomes in robotic-assisted partial nephrectomy.

BACKGROUND: Renal tumor scoring systems, such as the contact surface area value, aim to assist in predicting outcomes following robotic-assisted partial nephrectomy. The aim of this study is to identify associations between specific postoperative outcomes and the contact surface area of renal masses. METHODS: We analyzed 332 consecutive robotic-assisted partial nephrectomies and calculated contact surface area for renal tumors with the contact surface area formula (CSA = 2πrd), where π ≈ 3.14, r = greatest tumor radius (cm), and d = greatest tumor depth (cm). RESULTS: Higher contact surface area was associated with longer warm ischemia time (P < .001), higher estimated blood loss (P < .001), and longer length of hospital stay (LOS) (P < .001). Higher contact surface area was significantly associated with decreased renal function at 1 day, 1 month, and 6 months following robotic-assisted partial nephrectomy. CONCLUSIONS: Contact surface area is associated with certain outcomes following robotic-assisted partial nephrectomy and may be a useful predictive tool.

Contrast enhanced ultrasound characterization of surgically resected renal masses in patients on dialysis.

Objective: Diagnostic work-up of suspicious renal masses has traditionally been conducted with contrast-enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI). However, patients who are not candidates for intravenous contrast due to allergy, renal insufficiency, or those on dialysis are discouraged from utilizing traditional contrast imaging due to risks of anaphylaxis, nephrotoxicity, or further kidney damage. We evaluated contrast-enhanced ultrasound (CEUS) in patients on dialysis who would benefit from alternative imaging options to CECT or MRI.Methods: Following IRB approval, nine renal masses from eight patients (aged 54-74 years) with chronic renal insufficiency were evaluated with CEUS and shown to be enhancing after the intravenous administration of ultrasound contrast agent. The ultrasound contrast agent Lumason (Sulfur hexafluoride lipid type-A microspheres, Bracco Diagnostics, Monroe Township, NJ, USA) was utilized. Enhancement was considered present when microbubble contrast agent was visualized within the lesion of interest.Results: Nine CEUS enhancing masses were pathologically examined following laparoscopic radical nephrectomy. Eight of the nine lesions were renal cell carcinoma (two clear cell, four papillary, two cystic). One resected mass was an unspecified benign renal lesion.Conclusions: In this sample of surgically resected tumors, CEUS was effective in characterizing renal lesions as solid neoplasms or complex cystic lesions suspicious for neoplasm-findings which merit further investigation.