Impact of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in lymph nodal and mediastinal lesions: A multicenter experience.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an established procedure in lung cancer (LC) staging and in the diagnosis of mediastinal masses. Most of the experiences reported refer to single specialized centers where dedicated teams of endoscopists and pathologists perform the procedure. We report the EUS-FNA experience of a cooperation group involving clinicians and cytopathologists from three hospitals. Fifty-seven consecutive EUS-FNA of mediastinal nodes in LC patients, eight mediastinal and two subdiaphragmatic masses were collected in 3 years. EUS-FNA was performed by two endoscopists and three experienced pathologists. On-site evaluation was performed in all cases by the three cytopathologists. Lymph node negative cases underwent surgery, which confirmed the cytological diagnoses but also detected two false negatives. Four of the 10 EUS cytological diagnoses of mediastinal and subdiaphragmatic masses were histologically confirmed. All EUS diagnoses were blindly reviewed by three pathologists to assess intra and interpersonal reproducibility. FNA-EUS diagnoses were: 10 inadequate (17%), 10 negative (17%), 4 suspicious (7%) and 33 positive (59%). Diagnoses of mediastinal and subdiaphragmatic masses were: relapse of lung carcinoma (3), mesenchimal tumor not otherwise specifiable (3), gastrointestinal stromal tumor (GIST) (1), esophageal carcinoma (2) and paraganglioma (1). The sensitivity attained was 85% and the specificity 100%; revision of the slides demonstrated a significant diagnostic reproducibility of the three cytopathologists (P < 0.5). The sensitivity and specificity attained were similar to those reported in the literature suggesting that experienced cytopathologists and endoscopists from different institutions can employ the same procedure reaching comparable results

Mitochondria form contact sites with the nucleus to couple pro-survival retrograde response

Mitochondria drive cellular adaptation to stress by retro-communicating with the nucleus. This process is known as Mitochondrial Retrograde Response (MRR) and is induced by mitochondrial dysfunctions. MRR results in the nuclear stabilization of pro-survival transcription factors such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Here we demonstrate that MRR is facilitated by contact sites between mitochondria and the nucleus. The 18kD Translocator Protein (TSPO), which de-ubiquitylates and stabilizes the mitochondria thereby preventing their mitophagy-mediated segregation, is required for this interaction. The tethering TSPO enacts is mediated by the complex formed with the Protein kinase A (PKA) via the A-kinase anchoring protein Acyl-CoA Binding Domain Containing 3 (ACBD3) and allows the redistribution of cholesterol which sustains the pro-survival response by blocking NF-kB de-acetylation. This work proposes a new paradigm in the mitochondrial retro-communication by revealing the existence of contact sites between mitochondria and the nucleus and a signalling role for cholesterol