Circulating cell-free and extracellular vesicles-derived microRNA as prognostic biomarkers in patients with early-stage NSCLC: results from RESTING study.

BACKGROUND: Factors to accurately stratify patients with early-stage non-small cell lung cancer (NSCLC) in different prognostic groups are still needed. This study aims to investigate 1) the prognostic potential of circulating cell-free (CF) and extracellular vesicles (EVs)-derived microRNA (miRNAs), and 2) their added value with respect to known prognostic factors (PFs). METHODS: The RESTING study is a multicentre prospective observational cohort study on resected stage IA-IIIA patients with NSCLC. The primary end-point was disease-free survival (DFS), and the main analyses were carried out separately for CF- and EV-miRNAs. CF- and EV-miRNAs were isolated from plasma, and miRNA-specific libraries were prepared and sequenced. To reach the study aims, three statistical models were specified: one using the miRNA data only (Model 1); one using both miRNAs and known PFs (age, gender, and pathological stage) (Model 2), and one using the PFs alone (Model 3). Five-fold cross-validation (CV) was used to assess the predictive performance of each. Standard Cox regression and elastic net regularized Cox regression were used. RESULTS: A total of 222 patients were enrolled. The median follow-up time was 26.3 (95% CI 25.4-27.6) months. From Model 1, three CF-miRNAs and 21 EV-miRNAs were associated with DFS. In Model 2, two CF-miRNAs (miR-29c-3p and miR-877-3p) and five EV-miRNAs (miR-181a-2-3p, miR-182-5p, miR-192-5p, miR-532-3p and miR-589-5p) remained associated with DFS. From pathway enrichment analysis, TGF-beta and NOTCH were the most involved pathways. CONCLUSION: This study identified promising prognostic CF- and EV-miRNAs that could be used as a non-invasive, cost-effective tool to aid clinical decision-making. However, further evaluation of the obtained miRNAs in an external cohort of patients is warranted.

Sleeve Lobectomy: To Wrap or Not to Wrap the Bronchial Anastomosis?

BACKGROUND: Bronchoplastic procedures have become the reference standard in the lung parenchyma-sparing treatment of centrally located bronchopulmonary tumors. Two schools of thought exist regarding performing a bronchial sleeve resection: those who wrap the anastomosis with a pedicled flap and those who leave the anastomosis unprotected. We performed a study comparing these 2 methods. METHODS: This study was a retrospective multicenter observational analysis of 90 consecutive patients undergoing bronchial sleeve resections for neoplastic disease between June 2009 and July 2019. Group A (60 patients) underwent bronchial wrapping and group B (30 patients) did not undergo wrapping. RESULTS: The only difference between group A, which had 5 patients (8.3%), and group B, which had 10 patients (33.3%), regarding general characteristics was the presence of diabetes (P = .003). There were no differences in surgical, postoperative, and follow-up characteristics. There was no statistically significant difference between groups (group A, 9 patients [15%]; and group B, 6 patients [20%]) in terms of anastomotic complications at 1 year (P = .425). Diabetes was an independent predictive factor for anastomotic complications at 1 year (P = .035). The number of postoperative complications (P < .001) was an independent risk factor for length of hospital stay. CONCLUSIONS: We found no differences between groups in terms of postoperative complications and length of hospital stay, which confirmed previous reports that sleeve resections may be performed safely without bronchial wrapping.

Totally thoracoscopic versus standard VATS lobectomies: perioperative differences.

BACKGROUND: Minimally invasive surgery is considered the gold standard approach for early stage lung cancer. Techniques range from a standard three-port approach to uniportal lobectomies, with no technique emerging as superior thus far. We retrospectively compared the pain outcomes of a standard approach using a utility incision with a totally thoracoscopic technique. METHODS: Between January 2015 and December 2019, 168 patients received a VATS lobectomy in our centers. Two groups were created, Group A (82 patients, totally thoracoscopic approach) and Group B (86 patients, standard approach with utility incision). Perioperative outcomes, such as operative time, complications, length of stay, perioperative and chronic pain using visual analog scale (VAS), and rescue doses of painkillers were examined. A one-way analysis of covariance (ANCOVA) was conducted to investigate the impact of surgical time and days of drainage on VAS score. RESULTS: Pain was less on postoperative day (POD) 1 and 2 (p = 0.025 and p = 0.020, respectively) in Group A. No differences were found in the baseline and perioperative characteristics of the two groups, in the mean VAS score at 1 month (p = 0.429), 1 year (p = 0.561), doses of NSAIDs (p = 0.609), and chronic pain (3vs7 patients, p = 0.220). The ANCOVA test showed no significant effect of surgical time and days of drainage on VAS score (p > 0.05). CONCLUSIONS: In our experience, a totally thoracoscopic approach may improve acute postoperative pain without compromising the oncological results of the procedure and the safety of the patients.

The importance of diaphragmatic surgery, chemical pleurodesis and postoperative hormonal therapy in preventing recurrence in catamenial pneumothorax: a retrospective cohort study.

BACKGROUND: Catamenial pneumothorax (CP) is defined as a recurrent, spontaneous pneumothorax occurring within a day before or 72 h after the onset of menstruation. Most first episodes go undiagnosed and treated as primary spontaneous pneumothorax, and only after recurrence is the clinical suspicion of CP raised. No gold-standard management approach exists, especially in terms of managing diaphragmatic involvement. METHODS: This study is a single-centre cohort retrospective study of 24 female patients who underwent surgery for pneumothorax due to diaphragmatic endometriosis between January 2008 and December 2016. Two groups were compared: a group that underwent pleurodesis alone (8 patients) and a group that underwent diaphragmatic surgery and pleurodesis (16 patients). RESULTS: There were differences in BMI and smoking habits between the two groups. The right diaphragm was involved more often (6vs15, p = 0.190). VATS was the preferred surgical approach and only one conversion occurred in the diaphragmatic surgery group (p = 0.470). Diaphragmatic abnormalities were present in all the patients, brown/violet spots (100%) in the pleurodesis group and perforations (100%) in the diaphragmatic surgery group (p < 0.001). There were no differences in days of chest tube removal and length of stay. The recurrence rate was 100% in the pleurodesis alone group while it was only 12.5% in the diaphragmatic surgery group (< 0.001). CONCLUSIONS: In our experience, diaphragmatic surgery and pleurodesis followed by hormonal therapy was an effective approach in preventing recurrence in patients with catamenial pneumothorax and diaphragmatic involvement.

Penetrating left ventricular injuries management: single General Thoracic Center experience.

BACKGROUND: Left ventricular penetrating injuries are rare but often lethal. Transport times greater than 30 min have been shown to increase the injury severity; thus early recognition of cardiac tamponade, prompt pericardial decompression, and control of cardiac hemorrhage are mandatory. METHODS: We retrospectively reviewed our record to include patients with penetrating trauma of the heart. RESULTS: Four hemodynamically unstable young male patients with left ventricular penetrating injury of the heart were referred to our unit between January 2007 and December 2015. Median time from trauma to surgery was 16 min (range 14-21). A cardiorrhaphy through sternotomy with no extracorporeal support was performed. We had no in-hospital mortality. CONCLUSION: According to our experience, in patients with hemodynamic shock and penetrating cardiac injury, a timely recognition of injuries and referral to the closest thoracic surgery unit may increase patient survival if it is located closer than a level I trauma center.

Chondroblastoma of the rib in a 47-year-old man: a case report with a systematic review of literature.

Chondroblastoma is an uncommon benign bone tumour arising typically in the epiphysis. Few cases of chondroblastoma of the rib have been reported in the literature. We describe a case of chondroblastoma of a 47-year-old man located in the body of the IX right rib. The patient presented a moderate right thoracic pain with an apparently palpable mass. Computed tomography (CT) scan showed a well-defined oval 49 mm × 43 mm lesion with the lytic bone destruction of the rib. A surgical resection was performed with an excellent outcome and no recurrence after 4-year follow-up. We also conducted a systematic review of literature where we evidenced that chondroblastoma could affect people of all age, but it's most common in children and young adult. Surgical resection constitutes the treatment of choice.

Pneumonectomy after chemotherapy: morbidity, mortality, and long-term outcome.

BACKGROUND: Results of pneumonectomy after chemotherapy are controversial, and the procedure is often considered as potentially dangerous. METHODS: Records of patients who underwent pneumonectomy after chemotherapy for non-small cell lung cancer in a single institution in a 6-year period were reviewed retrospectively. RESULTS: One hundred eighteen patients had pneumonectomy after chemotherapy. Indications for preoperative chemotherapy were N2 disease, 74; potentially resectable T4 disease, 17; doubtful resectability, 18; stage IV disease (nodule on another ipsilateral lobe), 4; and participation in a randomized trial on induction chemotherapy in initial stages, 5. Chemotherapy protocols were platinum-based. Imaging reevaluation showed complete, partial, minor response, and disease stability in 0, 24, 39, and 55 patients, respectively. Operative mortality was 5.9% (7 of 118), consisting of 4 of 54 after pneumonectomy, and 3 of 64 after left pneumonectomy. Bronchopleural fistula caused one death. No factor among those evaluated (sex, age, comorbidities, forced expiratory volume in 1 second, symptoms, side and location of tumor; indication for operation, number of cycles, and response to chemotherapy; extent of resection, TNM status, pathologic stage) predicted postoperative death. Median and overall 5-year survival was 22 months and 23.7%, respectively. At univariate analysis, pathologic stage, T status, and the occurrence of postoperative complications influenced 5-year survival. At multivariate analysis, T status (p = 0.0054), the occurrence of postoperative complications (p = 0.0015), and clinical response to induction chemotherapy (p = 0.028) were identified as independent predictors of 5-year survival. CONCLUSIONS: Pneumonectomy after chemotherapy has acceptable mortality. Long-term results are encouraging.

Should we change antibiotic prophylaxis for lung surgery? Postoperative pneumonia is the critical issue.

BACKGROUND: The recommended antibiotic prophylaxis by second-generation cephalosporins reduces the incidence of wound infection and empyema, but its effectiveness on postoperative pneumonias (POPs) after major lung resection lacks demonstration. We investigated risk factors and characteristics of POPs occurring when antibiotic prophylaxis by second-generation cephalosporin or an alternative prophylaxis targeting organisms responsible for bronchial colonization was used. METHODS: An 18-month prospective study on all patients undergoing lung resections for noninfectious disease was performed. Prophylaxis by cefamandole (3 g/24 h, over 48 hours) was used during the first 6 months, whereas amoxicillin-clavulanate (6 g/24 h, over 24 hours) was used during the subsequent 12 months. Intraoperative bronchial aspirates were systematically cultured. Patients with suspicion of pneumonia underwent bronchoscopic sampling for culture. RESULTS: Included were 168 patients in the first period and 277 patients in the second period. The incidence of POP decreased by 45% during the second period (P = 0.0027). A significant reduction in antibiotic therapy requirement for postoperative infections (P = 0.0044) was also observed. Thirty-day mortality decreased from 6.5% to 2.9% (P = 0.06). Multivariate analysis showed that type of resection, intraoperative colonization, chronic obstructive pulmonary disease, gender, body mass index, and type of prophylaxis were independent risk factors of POP. A case control-study that matched patients of the two periods according to these risk factors (except for antibiotic prophylaxis) confirmed that the incidence of POP was lowered during the second period. CONCLUSIONS: Targeted antibiotic prophylaxis may decrease the rate of POPs after lung resection and improve outcome.

The Budapest Meeting 2005 intensified networking on ethics of science: the case of reproductive cloning, germline gene therapy and human dignity.

This paper reports on the meeting of the Sounding Board of the EU Reprogenetics Project that was held in Budapest, Hungary, 6-9 November 2005. The Reprogenetics Project runs from 2004 until 2007 and has a brief to study the ethical aspects of human reproductive cloning and germline gene therapy. Discussions during The Budapest Meeting are reported in depth in this paper as well as the initiatives to involve the participating groups and others in ongoing collaborations with the goal of forming an integrated network of European resources in the fields of ethics of science.

Conflict of interest in biomedical research: a view from Europe.

In this paper I address the conflict of interest (CoI) issue from a legal point of view at a European level. We will see that the regulatory framework that exists in Europe does state the need for the independence of ethics committee involved in authorisation of research and clinical trials. We will see that CoI is an element that has to be closely monitored at National and International level. Therefore, Member States and Newly Associated States do have to address CoI in the authorisation process of research and clinical protocols of biomedicine.

Genetics' dreams in the post genomics era.

In this paper I explore the heuristic limits of human genetics, in particular the claim that it is possible to manipulate human germ cells in a pre-ordinate way (Gordon, 1999). I argue that this claim is unrealistic based on genetic reductionism and a wrong concept of genetic diseases.