Amplification of the MET oncogene is associated with poor prognosis, metastatic dissemination, and drug resistance in many malignancies. We developed a method to capture and characterize circulating tumor cells (CTC) expressing c-MET using a ferromagnetic antibody. Immunofluorescence was used to characterize cells for c-MET, DAPI, and pan-CK, excluding CD45 þ leukocytes. The assay was validated using appropriate cell line controls spiked into peripheral blood collected from healthy volunteers (HV). In addition, peripheral blood was analyzed from patients with metastatic gastric, pancreatic, colorectal, bladder, renal, or prostate cancers. CTCs captured by c-MET were enumerated, and DNA FISH for MET amplification was performed. The approach was highly sensitive (80%) for MET-amplified cells, sensitive (40%-80%) for c-MET-overexpressed cells, and specific (100%) for both c-MET-negative cells and in 20 HVs. Of 52 patients with metastatic carcinomas tested, c-MET CTCs were captured in replicate samples from 3 patients [gastric, colorectal, and renal cell carcinoma (RCC)] with 6% prevalence. CTC FISH demonstrated that MET amplification in both gastric and colorectal cancer patients and trisomy 7 with gain of MET gene copies in the RCC patient. The c-MET CTC assay is a rapid, noninvasive, sensitive, and specific method for detecting MET-amplified tumor cells. CTCs with MET amplification can be detected in patients with gastric, colorectal, and renal cancers.Implications: This study developed a novel c-MET CTC assay for detecting c-MET CTCs in patients with MET amplification and warrants further investigation to determine its clinical applicability.
Objective: Extracorporeal membrane oxygenation (ECMO) is increasingly employed in the management of patients with severe cardiac and pulmonary dysfunction. Patients commonly require tracheostomy for ventilator liberation. Though bedside percutaneous tracheostomy is commonly performed, it has the potential for increased complications, both surgical and with the ECMO circuit. We examined surgical outcomes of bedside percutaneous tracheostomy in the ECMO population. Methods: Patients were identified from an institutional database for bedside procedures. Demographics and data on complications were recorded. Descriptive statistics were calculated. Results: 37 patients on ECMO at the time of tracheostomy were identified. Median age and BMI were 43.2 and 28.0, respectively. 33 patients (89%) were on VV ECMO, and 4 (11%) were on VA ECMO. All were on anticoagulation prior to tracheostomy, which was held for 4 h before and after the procedure in all cases. There were no procedure-related deaths or airway losses. No patients experienced periprocedural clotting events of their ECMO circuit or oxygenator within 24 h. 3 patients (8%) required reintervention (re-exploration or bronchoscopy) for bleeding. Four other patients (10%) had minor bleeding controlled with packing. One patient had pneumomediastinum which resolved without intervention, and one had an occlusion of their tracheostomy which was treated with tracheostomy exchange. Conclusions: Bedside percutaneous tracheostomy is feasible for patients on ECMO. Further study is needed to determine specific risk factors for complications and means to mitigate these. Bedside percutaneous tracheostomy may be considered as part of the management of patients on ECMO to help facilitate liberation from mechanical support.
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