Neuroendocrine Gene Subsets Are Uniquely Dysregulated in Prostate Adenocarcinoma

Prostate cancer has heterogeneous growth patterns, and its prognosis is the poorest when it progresses to a neuroendocrine phenotype. Using bioinformatic analysis, we evaluated RNA expression of neuroendocrine genes in a panel of five different cancer types: prostate adenocarcinoma, breast cancer, kidney chromophobe, kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. Our results show that specific neuroendocrine genes are significantly dysregulated in these tumors, suggesting that they play an active role in cancer progression. Among others, synaptophysin (SYP), a conventional neuroendocrine marker, is upregulated in prostate adenocarcinoma (PRAD) and breast cancer (BRCA). Our analysis shows that SYP is enriched in small extracellular vesicles (sEVs) derived from plasma of PRAD patients, but it is absent in sEVs derived from plasma of healthy donors. Similarly, classical sEV markers are enriched in sEVs derived from plasma of prostate cancer patients, but weakly detectable in sEVs derived from plasma of healthy donors. Overall, our results pave the way to explore new strategies to diagnose these diseases based on the neuroendocrine gene expression in patient tumors or plasma sEVs

Implanted atrial pacemakers for paroxysmal atrial flutter. Long-term efficacy

Five patients with drug-resistant paroxysmal atrial flutter received permanent burst atrial pacemakers for the treatment of tachycardia. All patients had extensive electrophysiologic evaluations to determine the safety and efficacy of atrial pacing. The absence of prolonged spontaneous or electrically induced atrial fibrillation was also documented in all patients. Three pulse generators were patient activated (nonautomatic) and two were multiprogrammable and automatic. The atrial pacemakers terminated many attacks of paroxysmal atrial flutter safely and reliably in a follow-up period ranging from 24 to 60 months (average, 42). No major complications developed. In four patients, concomitant drug therapy was necessary, although to a lesser degree, to reduce the frequency of attacks and the ventricular rate. Our study documents the long-term efficacy and low risk associated with permanent-burst atrial pacing in the treatment of drug-refractory paroxysmal atrial flutter in selected patients