Lung cancer burden can be reduced by adopting primary and secondary prevention strategies such as anti-smoking campaigns and low-dose CT screening for high risk subjects (aged >50 and smokers >30 packs/year). Recent CT screening trials demonstrated a stage-shift towards earlier stage lung cancer and reduction of mortality (~20%). However, a sizable fraction of patients (30–50%) with early stage disease still experience relapse and an adverse prognosis. Thus, the identification of effective prognostic biomarkers in stage I lung cancer is nowadays paramount. Here, we applied a multi-tiered approach relying on coupled RNA-seq and miRNA-seq data analysis of a large cohort of lung cancer patients (TCGA-LUAD, n = 510), which enabled us to identify prognostic miRNA signatures in stage I lung adenocarcinoma. Such signatures showed high accuracy (AUC ranging between 0.79 and 0.85) in scoring aggressive disease. Importantly, using a network-based approach we rewired miRNA-mRNA regulatory networks, identifying a minimal signature of 7 miRNAs, which was validated in a cohort of FFPE lung adenocarcinoma samples (CSS, n = 44) and controls a variety of genes overlapping with cancer relevant pathways. Our results further demonstrate the reliability of miRNA-based biomarkers for lung cancer prognostication and make a step forward to the application of miRNA biomarkers in the clinical routine.

The silencing of SPARC (secreted protein acid and rich in cysteine) gene through methylation of its promoter region represents a common event in many solid tumors and it is frequently associated with tumor progression and an aggressive clinical outcome. Anyhow, the data concerning the epigenetic mechanism of SPARC deregulation and its prognostic value in lung cancer are still incomplete. We explored the aberrant methylation of SPARC and its effects in 4 non-small cell lung cancer (NSCLC) cell lines and 59 NSCLC tissues and correlated the methylation levels with clinical-pathological features and disease outcome of patients. In 3 out of 4 tumor cell lines high SPARC methylation levels were observed. An inverse correlation between the epigenetic silencing and SPARC expression was confirmed by 5-Aza-2′-deoxycytidine ((5-Aza-CdR) treatment that also significantly induced a reduction in cell viability, proliferation and tumor cell migration. In tissues, the DNA methylation levels of the SPARC gene were significantly lower in paired non-neoplastic lungs (NLs) and normal lungs distant from tumor (NLDTs) than in NSCLCs (p = 0.002 and p = 0.0034 respectively). A promoter hypermethylation was detected in 68% of squamous cell carcinoma (SqCCs, 17/25) and 56% of adenocarcinoma (ADCs, 19/34), with SqCC showing the highest levels of methylation. Higher SPARC methylation levels were significantly associated with higher mortality risk both in all NSCLCs early stage patients (Hazard Ratio, HR = 1.97; 95% Confidence Interval, CI: 1.32–2.93; p = 0.001) and in those with SqCC (HR = 2.96; 95% CI: 1.43–6.12; p = 0.003). Promoter methylation of SPARC gene should represent an interesting prognostic biomarker in NSCLC, with potential application in the squamous early-stage context. Further research in this setting on larger independent cohorts of lung patients with different histologies and stages of disease are warranted.

Background: The primary aim of this study was to confirm the validity of intraoperative lung ultrasound (ILU) as a safe and effective method of localization for difficult to visualize pulmonary nodules during Video-Assisted Thoracoscopic Surgery (VATS) and open thoracotomy. The secondary aim was to enhance knowledge on the morphological patterns of presentation of pulmonary nodules on direct ultrasound examination. Materials and methods: 131 patients with lung nodule and indication for surgery were enrolled. All patients underwent pre-operative imaging of the chest, including Chest Computed Tomography (CT) and Transthoracic Ultrasound (TUS), and surgical procedures for histological assessment of pulmonary nodules (VATS or open thoracotomy). Results: The identification of 100.00% of lung nodules was allowed by ILU, while the detection rate of digital palpation was 94.66%. It was not possible to associate any specific ILU echostructural pattern to both benign or malignant lesions. However, the actual histological margins of the lesions in the operating samples were corresponding to those visualized at ILU in 125/131 (95.42%) cases. No complications have been reported with ILU employment. Conclusions: In our experience, ILU performed during both open surgery and VATS demonstrated to be a reliable and safe method for visualization and localization of pulmonary nodules non previously assessed on digital palpation. In addition, ILU showed to allow a clear nodule’s margins’ definition matching, in most cases, with the actual histological margins.

(1) Background: The aim of this study was to conduct a prospective analysis on the diagnostic accuracy of transthoracic ultrasound-guided percutaneous needle biopsy (TUS-PNB) for the histological assessment of peripheral lung lesions and to assess the performance of transthoracic ultrasound (TUS) examination vs. chest CT (gold standard) in the differentiation between malignant and benign peripheral lung lesions. (2) Methods: A total of 961 consecutive patients with subpleural pulmonary lesions were enrolled. All the patients received a CT scan with contrast; 762 patients underwent TUS-PTNB for suspicion of malignancy, and the remaining 199 enrolled patients underwent only TUS examination as a part of routine follow-up for known non-malignant subpleural consolidations. (3) Results: Among the 762 TUS-guided biopsies, there were 627 (82.28%) malignant lesions, 82 (10.76%) benign lesions, and 53 (6.96%) indeterminate lesions. The overall diagnostic accuracy was 93.04%. The rates of pneumothorax not requiring chest-tube insertion and self-limited hemoptysis were 0.79 and 0.26%, respectively. Patients were divided into two groups based on the benign or malignant nature of the subpleural consolidations. On TUS, both malignant and benign lesions showed mostly irregular margins and a hypoechoic pattern, but no differences were assessed in terms of sonographic margins and pattern between the two groups. There was poor agreement between TUS and chest CT in assessing air bronchograms and necrotic areas. The only finding in the detection of which TUS showed superiority compared to chest-CT was pleural effusion. (4) Conclusions: TUS-PNB was confirmed to be an effective and safe diagnostic method for peripheral pulmonary consolidation, but their sonographic pattern did not allow to rule out a malignant nature. A pre-operative evaluation on CT images, combined with the possibility of performing additional immunohistochemical and cytological investigations and the experience of the medical staff, may improve the diagnostic yield of TUS-guided biopsies.

Esophageal diverticulum is a rare disease caused by impairment of esophageal motility. The incidence is not known, due to lack of symptoms in many cases. Surgical treatment is reserved to symptomatic patients. In this case report, we describe a rare case of epiphrenic esophageal diverticulum. A 61-year-old male with silent medical history, suffering severe chest pain had a CT scan showing a large esophageal diverticulum. The patient was referred to our hospital, IRCCS “Casa Sollievo della Sofferenza”, to complete pre-operative assessment with a CT scan and a Barium swallowing radiography, giving morphodimensional details of the diverticulum. Based on these findings, the surgeons have chosen the appropriate operative strategy. The surgeons adopted a laparoscopic access, completed with robotic-assisted laparotomy due to the morphology of the diverticulum. Radiological evaluation is crucial in the diagnosis and in the treatment planning of symptomatic patients.