RESUMO
Circulating tumor cells (CTC) have been studied in various solid tumors but clinical utility of CTC in small cell lung cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics. CTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC. CD56+ CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to whole-exome-sequencing (WES). Phenotypic study confirms tumor lineage and tumorigenic properties of isolated cells for the 4 patients analyzed with WES. WES of CD56+ CTC and matched tumor biopsy reveal genomic alteration frequently impaired in SCLC. At diagnosis CD56+ CTC were characterized by a high mutation load, a distinct mutational profile and a unique genomic signature, compared to match tumors biopsies. In addition to classical pathways altered in SCLC, we found new biological processes specifically affected in CD56+ CTC at diagnosis. High numeration of CD56+ CTC (> 7/ml) at diagnosis was associated with ES-SCLC. Comparing CD56+ CTC isolated at diagnosis and relapse, we identify differentially altered oncogenic pathways (e.g. DLL3 or MAPK pathway). We report a versatile method of CD56+ CTC detection in SCLC. Numeration of CD56+ CTC at diagnosis is correlated with disease extension. Isolated CD56+ CTC are tumorigenic and show a distinct mutational profile. We report a minimal gene set as a unique signature of CD56+ CTC and identify new affected biological pathways enriched in EpCAM-independent isolated CTC in SCLC.
Assuntos
Neoplasias Pulmonares , Células Neoplásicas Circulantes , Carcinoma de Pequenas Células do Pulmão , Humanos , Molécula de Adesão da Célula Epitelial , Relevância Clínica , Estudos Prospectivos , Genômica , Carcinogênese , Proteínas de Membrana , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
PURPOSE: To evaluate the safety and feasibility of peripheral percutaneous endovascular procedures in a large group of outpatients with peripheral arterial disease (PAD). MATERIALS AND METHODS: We retrospectively evaluated all consecutive patients who underwent peripheral transluminal angioplasty (PTA) for PAD of the lower extremities as "Out-Patient Admission Protocol" (OPAP) from January 2005 until December 2015. A total of 498 consecutive patients (305 men and 193 women) with mean age of 66±10 (SD) years (range: 37-90 years) were evaluated. By protocol, patients were expected to be discharged 6hours after the procedure. Clinical profile, procedure details and technical success were reviewed. Complications, conversion rate, readmission rate and long-term follow-up were evaluated. RESULTS: Ninety one percent of patients (454/498) suffered from claudication. Unilateral femoral access was performed in 75.4% (493/654) of procedures with a 6-French sheath in 80.7% (528/654) of procedures. Balloon PTA alone was performed in 17.3% (148/857) and stent placement in 82.7% (709/857) of treated segments. Technical success of lesion treatment was 98.2% (857/873). Closure devices were used in 55.4% (362/654) of procedures. Conversion and readmission rates were 1.8% (12/654) and 0.6% (4/654), respectively. Long-term follow-up was obtained in 386 target lesions, 5-year restenosis of lesion was 20.5% (79/386). CONCLUSION: As designed, the OPAP was feasible, safe and effective with very low conversion and complications rates. These results strongly support a larger use of such approaches as routine practice.