Genetic predisposition to lung adenocarcinoma outcome is a feature already present in patients' noninvolved lung tissue.

Emerging evidence suggests that the prognosis of patients with lung adenocarcinoma can be determined from germline variants and transcript levels in nontumoral lung tissue. Gene expression data from noninvolved lung tissue of 483 lung adenocarcinoma patients were tested for correlation with overall survival using multivariable Cox proportional hazard and multivariate machine learning models. For genes whose transcript levels are associated with survival, we used genotype data from 414 patients to identify germline variants acting as cis-expression quantitative trait loci (eQTLs). Associations of eQTL variant genotypes with gene expression and survival were tested. Levels of four transcripts were inversely associated with survival by Cox analysis (CLCF1, hazard ratio [HR] = 1.53; CNTNAP1, HR = 2.17; DUSP14, HR = 1.78; and MT1F: HR = 1.40). Machine learning analysis identified a signature of transcripts associated with lung adenocarcinoma outcome that was largely overlapping with the transcripts identified by Cox analysis, including the three most significant genes (CLCF1, CNTNAP1, and DUSP14). Pathway analysis indicated that the signature is enriched for ECM components. We identified 32 cis-eQTLs for CNTNAP1, including 6 with an inverse correlation and 26 with a direct correlation between the number of minor alleles and transcript levels. Of these, all but one were prognostic: the six with an inverse correlation were associated with better prognosis (HR < 1) while the others were associated with worse prognosis. Our findings provide supportive evidence that genetic predisposition to lung adenocarcinoma outcome is a feature already present in patients' noninvolved lung tissue.

Lung Transplantation From Controlled and Uncontrolled Donation After Circulatory Death (DCD) Donors With Long Ischemic Times Managed by Simple Normothermic Ventilation and Ex-Vivo Lung Perfusion Assessment.

Donation after cardiac death (DCD) donors are still subject of studies. In this prospective cohort trial, we compared outcomes after lung transplantation (LT) of subjects receiving lungs from DCD donors with those of subjects receiving lungs from donation after brain death (DBD) donors (ClinicalTrial.gov: NCT02061462). Lungs from DCD donors were preserved in-vivo through normothermic ventilation, as per our protocol. We enrolled candidates for bilateral LT ≥14 years. Candidates for multi-organ or re-LT, donors aged ≥65 years, DCD category I or IV donors were excluded. We recorded clinical data on donors and recipients. Primary endpoint was 30-day mortality. Secondary endpoints were: duration of mechanical ventilation (MV), intensive care unit (ICU) length of stay, severe primary graft dysfunction (PGD3) and chronic lung allograft dysfunction (CLAD). 121 patients (110 DBD Group, 11 DCD Group) were enrolled. 30-day mortality and CLAD prevalence were nil in the DCD Group. DCD Group patients required longer MV (DCD Group: 2 days, DBD Group: 1 day, p = 0.011). ICU length of stay and PGD3 rate were higher in DCD Group but did not significantly differ. LT with DCD grafts procured with our protocols appears safe, despite prolonged ischemia times.

Italian survey on non-intubated thoracic surgery: results from INFINITY group.

BACKGROUND: Non-Intubated Thoracic Surgery (NITS) is becoming increasingly adopted all over the world. Although it is mainly used for pleural operations,, non-intubated parenchymal lung surgery has been less frequently reported. Recently, NITS utilization seems to be increased also in Italy, albeit there are no multi-center studies confirming this finding. The objective of this survey is to assess quantitatively and qualitatively the performance of NITS in Italy. METHODS: In 2018 a web-based national survey on Non-Intubated management including both thoracic surgeons and anesthesiologists was carried out. Reference centers have been asked to answer 32 questions. Replies were collected from June 26 to November 31, 2019. RESULTS: We raised feedbacks from 95% (55/58) of Italian centers. Seventy-eight percent of the respondents perform NITS but only 38% of them used this strategy for parenchymal surgery. These procedures are more frequently carried out in patients with severe comorbidities and/or with poor lung function. Several issues as obesity, previous non-invasive ventilation and/or oxygen therapy are considered contraindications to NITS. The regional anesthesia technique most used to provide intra- and postoperative analgesia was the paravertebral block (37%). Conversion to general anesthesia is not anecdotal (31% of answerers). More than half of the centers believed that NITS may reduce postoperative intensive care unit admissions. Approximately a quarter of the centers are conducting trials on NITS and, three quarters of the respondent suppose that the number of these procedures will increase in the future. CONCLUSIONS: There is a growing interest in Italy for NITS and this survey provides a clear view of the national management framework of these procedures.

Read-through transcripts in lung: germline genetic regulation and correlation with the expression of other genes.

Transcripts originating from the transcriptional read through of two adjacent, similarly oriented genes have been identified in normal and neoplastic tissues, but their functional role and the mechanisms that regulate their expression are mostly unknown. Here, we investigated whether the expression of read-through transcripts previously identified in the non-involved lung tissue of lung adenocarcinoma patients was genetically regulated. Data on genome-wide single nucleotide variant genotypes and expression levels of 10 read-through transcripts in 201 samples of lung tissue were combined to identify expression quantitative trait loci (eQTLs). Then, to identify genes whose expression levels correlated with the 10 read-through transcripts, we used whole transcriptome profiles available for 154 patients. For 8 read-though transcripts, we identified 60 eQTLs (false discovery rate <0.05), including 17 cis-eQTLs and 43 trans-eQTLs. These eQTLs did not maintain their behavior on the 'parental' genes involved in the read-through transcriptional event. The expression levels of 7 read-through transcripts were found to correlate with the expression of other genes: CHIA-PIFO and CTSC-RAB38 correlated with CHIA and RAB38, respectively, while 5 other read-through transcripts correlated with 43 unique non-parental transcripts; thus offering indications about the molecular processes in which these chimeric transcripts may be involved. We confirmed 9 eQTLs (for 4 transcripts) in the non-involved lung tissue from an independent series of 188 lung adenocarcinoma patients. Therefore, this study indicates that the expression of four read-through transcripts in normal lung tissue is under germline genetic regulation, and that this regulation is independent of that of the genes involved in the read-through event.

Early pulmonary function and mid-term outcome in lung transplantation after ex-vivo lung perfusion - a single-center, retrospective, observational, cohort study.

Outcomes after transplantation of lungs (LuTX) treated with ex-vivo lung perfusion (EVLP) are debated. In a single-center 8 years of retrospective analysis, we compared: donors' and recipients' characteristics, gas exchange and lung mechanics at ICU admission, 3, 6, and 12 months, and patients' survival of LuTX from standard donors compared with EVLP-treated grafts. A total of 193 LuTX were performed. Thirty-one LuTX, out of 50 EVLP procedures, were carried out: 7 from nonheart beating and 24 from extended criteria brain-dead donors. Recipients' characteristics were similar. At ICU admission, compared with standard donors, EVLP patients had worse PaO2 /FiO2 [276 (206; 374) vs. 204 (133; 245) mmHg, P < 0.05], more frequent extracorporeal support (18% vs. 32%, P = 0.053) and longer mechanical ventilation duration [28 days of ventilator-free days: 27 (24; 28) vs. 26 (19; 27), P < 0.05]. ICU length of stay [4 (2; 9) vs. 6 (3; 12) days, P = 0.208], 28-day survival (99% vs. 97%, P = 0.735), and 1-year respiratory function were similar between groups. Log-rank analysis (median follow-up 2.5 years) demonstrated similar patients' survival (P = 0.439) and time free of chronic lung allograft disease (P = 0.484). The EVLP program increased by 16% the number of LuTX. Compared to standard donors, EVLP patients had worse respiratory function immediately after LuTX but similar early and mid-term outcomes.

How Data Analytics and Big Data Can Help Scientists in Managing COVID-19 Diffusion: Modeling Study to Predict the COVID-19 Diffusion in Italy and the Lombardy Region.

BACKGROUND: COVID-19 is the most widely discussed topic worldwide in 2020, and at the beginning of the Italian epidemic, scientists tried to understand the virus diffusion and the epidemic curve of positive cases with controversial findings and numbers. OBJECTIVE: In this paper, a data analytics study on the diffusion of COVID-19 in Italy and the Lombardy Region is developed to define a predictive model tailored to forecast the evolution of the diffusion over time. METHODS: Starting with all available official data collected worldwide about the diffusion of COVID-19, we defined a predictive model at the beginning of March 2020 for the Italian country. RESULTS: This paper aims at showing how this predictive model was able to forecast the behavior of the COVID-19 diffusion and how it predicted the total number of positive cases in Italy over time. The predictive model forecasted, for the Italian country, the end of the COVID-19 first wave by the beginning of June. CONCLUSIONS: This paper shows that big data and data analytics can help medical experts and epidemiologists in promptly designing accurate and generalized models to predict the different COVID-19 evolutionary phases in other countries and regions, and for second and third possible epidemic waves.

Clarification of Misleading Perceptions of COVID-19 Fatality and Testing Rates in Italy: Data Analysis.

BACKGROUND: The fatality rate of coronavirus disease (COVID-19) in Italy is controversial and is greatly affecting discussion on the impact of containment measures that are straining the world's social and economic fabric, such as instigating large-scale isolation and quarantine, closing borders, imposing limits on public gatherings, and implementing nationwide lockdowns. OBJECTIVE: The scientific community, citizens, politicians, and mass media are expressing concerns regarding data suggesting that the number of COVID-19-related deaths in Italy is significantly higher than in the rest of the world. Moreover, Italian citizens have misleading perceptions related to the number of swab tests that have actually been performed. Citizens and mass media are denouncing the coverage of COVID-19 swab testing in Italy, claiming that it is not in line with that in other countries worldwide. METHODS: In this paper, we attempt to clarify the aspects of COVID-19 fatalities and testing in Italy by performing a set of statistical analyses that highlight the actual numbers in Italy and compare them with official worldwide data. RESULTS: The analysis clearly shows that the Italian COVID-19 fatality and mortality rates are in line with the official world scenario, as are the numbers of COVID-19 tests performed in Italy and in the Lombardy region. CONCLUSIONS: This up-to-date analysis may elucidate the evolution of the COVID-19 pandemic in Italy.

Germline polymorphisms and survival of lung adenocarcinoma patients: a genome-wide study in two European patient series.

In lung cancer, the survival of patients with the same clinical stage varies widely for unknown reasons. In this two-phase study, we examined the hypothesis that germline variations influence the survival of patients with lung adenocarcinoma. First, we analyzed existing genotype and clinical data from 289 UK-resident patients with lung adenocarcinoma, identifying 86 single nucleotide polymorphisms (SNPs) that associated with survival (p < 0.01). We then genotyped these candidate SNPs in a validation series of 748 patients from Italy that resulted genetically compatible with the UK series based on principal component analysis. In a Cox proportional hazard model adjusted for age, sex and clinical stage, four SNPs were confirmed on the basis of their having a hazard ratio (HR) indicating the same direction of effect in the two series and p < 0.05. The strongest association was provided by rs2107561, an intronic SNP of PTPRG, protein tyrosine phosphatase, receptor type, G; the C allele was associated with poorer survival in both patient series (pooled analysis loge HR = 0.31; 95% CI: 0.15-0.46, p = 8.5 × 10(-5) ). PTPRG mRNA levels in 43 samples of lung adenocarcinoma were 40% of those observed in noninvolved lung tissue from the same patients. PTPRG overexpression significantly inhibited the clonogenicity of A549 lung carcinoma cells and the anchorage-independent growth of the NCI-H460 large cell lung cancer line. These four germline variants represent promising candidates that, with further study, may help predict clinical outcome. In addition, the PTPRG locus may have a role in tumor progression.

Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation.

This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2 /FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40-84] vs. 39 [36-46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953).

Gene expression signature of non-involved lung tissue associated with survival in lung adenocarcinoma patients.

Lung adenocarcinoma patients of similar clinical stage and undergoing the same treatments often have marked interindividual variations in prognosis. These clinical discrepancies may be due to the genetic background modulating an individual's predisposition to fighting cancer. Herein, we hypothesized that the lung microenvironment, as reflected by its expression profile, may affect lung adenocarcinoma patients' survival. The transcriptome of non-involved lung tissue, excised from a discovery series of 204 lung adenocarcinoma patients, was evaluated using whole-genome expression microarrays (with probes corresponding to 28 688 well-annotated coding sequences). Genes associated with survival status at 60 months were identified by Cox regression analysis (adjusted for gender, age and clinical stage) and retested in a validation series of 78 additional cases. RNA-Seq analysis from non-involved lung tissue of 12 patients was performed to characterize the different isoforms of candidate genes. Ten genes for which the loge-transformed hazard ratios expressed the same direction of effect in the discovery (P < 1.0 × 10(-3)) and validation series comprised the gene expression signature associated with survival: CNTNAP1, PKNOX1, FAM156A, FRMD8, GALNTL1, TXNDC12, SNTB1, PPP3R1, SNX10 and SERPINH1. RNA sequencing highlighted the complex expression pattern of these genes in non-involved lung tissue from different patients and permitted the detection of a read-through gene fusion between PPP3R1 and the flanking gene (CNRIP1) as well as a novel isoform of CNTNAP1. Our findings support the hypothesis that individual genetic characteristics, evidenced by the expression pattern of non-involved tissue, influence the outcome of lung adenocarcinoma patients.

Advances in Lung Transplantation.

Nowadays, lung transplantation is a clinical reality for the treatment of benign end-stage respiratory diseases [...].

Approaches and outcomes of Robotic-Assisted Thoracic Surgery (RATS) for lung cancer: a narrative review.

Robotic-Assisted Thoracic Surgery (RATS) is considered one of the main issues of present thoracic surgery. RATS is a minimally invasive surgical technique allowing enhanced view, accurate and complex movements, and high ergonomics for the surgeon. Despite these advantages, its application in lung procedures has been limited, mainly by its costs. Since now many different approaches have been proposed and the experience in RATS for lungs ranges from wedge resection to pneumonectomy and is mainly related to lung cancer. The present narrative review explores main approaches and outcomes of RATS lobectomy for lung cancer. A non-systematic review of literature was conducted using the PubMed search engine. An overview of lung robotic surgery is given, and main approaches of robotic lobectomy for lung cancer are exposed. Initial experiences of biportal and uniportal RATS are also described. So far, retrospective analysis reported satisfactory robotic operative outcomes, and comparison with VATS might suggest a more accurate lymphadenectomy. Some Authors might even suggest better perioperative outcomes too. From an oncological standpoint, no definitive prospective study has yet been published but several retrospective analyses report oncological outcomes comparable to those of VATS and open surgery. Literature suggests that RATS for lung procedures is safe and effective and should be considered as a valid additional surgical option.

A real-world experience of transition to robotic-assisted thoracic surgery (RATS) for lung resections.

Objective: We report our experience of transition to robotic-assisted thoracic surgery (RATS) for lung resections with the da Vinci Xi surgical system, exposing short-term results. Materials and methods: This is a single-center, retrospective analysis of RATS lung resections performed between April 2021 and September 2022 during our new robotic program. The surgical approach evolved over time, starting from a four-arm approach with four incisions. Alternative RATS approaches were subsequently evaluated, such as uniportal and biportal. Results: During a 17-month period, 29 lung resections were performed. Of them, 16 were lobectomies, 7 were segmentectomies, and 6 were wedge resections. The most common indication for anatomical lung resection was non-small cell lung cancer. A uniportal approach was used for two simple segmentectomies and a biportal RATS was performed in five lobectomies and two segmentectomies. A mean number of 8.1 lymph nodes and a mean of 2.6 N2 and 1.9 N1 stations were resected during surgery, and no nodal upstaging was observed. Negative resection margins were 100%. There were two (7%) conversions, one to open surgery and one to video-assisted thoracic surgery (VATS). Eight (28%) patients experienced complications with no 30-day mortality. Discussion: High-ergonomic and high-quality views were immediately observed. After some procedures, we abandoned uniportal RATS because of the possibility of arm collisions and the necessity of a VATS-skilled surgeon at the operating table. Conclusion: RATS for lung resections was safe and effective, and from the surgeon's standpoint, several practical advantages over VATS were observed. Further analysis on outcomes will help better understand the value of this technology.

Pneumonectomy for Unilateral Proximal Interruption of Pulmonary Artery: A Case Series from the Literature.

BACKGROUND: Unilateral proximal interruption of the pulmonary artery (UPIPA) is a rare congenital disease, and its optimal management remains undefined in the existing literature. The occasional necessity for pneumonectomy is still supported by limited evidence. METHODS: A systematic review of the literature was conducted using the PubMed search engine, focusing on UPIPA cases that received pneumonectomy. Thirty-one pertinent articles were selected and included in the analysis. A case reported from our institution was included in the analysis. RESULTS: We found 25 adults and seven children affected by UPIPA who received an indication for pneumonectomy, plus an additional case that was reported by our institution. Among adult patients, the predominant indication was hemoptysis (57%), followed by suspected or confirmed lung cancer (23%). Approximately 46% of surgical procedures were classified as urgent or emergent. Postoperative complications were observed in 36% of cases, with no recorded mortality. In pediatric cases, pneumonectomy was primarily a life-saving intervention, performed urgently or emergently in 75% of instances. A possible late complication in pediatric patients involves a mediastinal shift leading to respiratory distress, which may be mitigated using an inflatable prosthesis. CONCLUSIONS: Pneumonectomy achieves complete resolution of UPIPA symptoms. In the adult population, its primary indication is hemoptysis, with procedures conducted in both elective and urgent/emergent settings. Despite a mortality rate of zero, a notable proportion of patients may experience postoperative complications. In pediatric cases, the clinical presentation varies more extensively, and pneumonectomy is typically reserved for life-threatening situations, emphasizing the need for careful patient selection.

Oncological Outcomes of Segmentectomy versus Lobectomy in Clinical Stage I Non-Small Cell Lung Cancer up to Two Centimeters: Systematic Review and Meta-Analysis.

OBJECTIVE: In recent years, pulmonary segmentectomy has emerged as an alternative to lobectomy for the treatment of patients with clinical stage I non-small cell lung cancer. Considering the conflicting results reported in the literature, the oncological effectiveness of segmentectomy remains controversial. To provide new insight into oncological results, we reviewed the literature, including recent randomized trials. METHODS: We performed a systematic review for surgical treatment of stage I NSCLC up to 2 cm using MEDLINE and the Cochrane Database from 1990 to December 2022. Primary outcomes for pooled analysis were overall and disease-free survival; secondary outcomes were postoperative complications and 30-day mortality. RESULTS: Eleven studies were considered for the meta-analysis. The pooled analysis included 3074 and 2278 patients who received lobectomy and segmentectomy, respectively. The estimated pooled hazard ratio showed a similar hazard for segmentectomy compared to lobectomy in terms of overall and disease-free survival. The restricted mean survival time difference between the two procedures was statistically and clinically not significant for overall and disease-free survival. Nevertheless, the overall survival hazard ratio was time-dependent: segmentectomy was at a disadvantage starting from 40 months after surgery. Six papers reported 30-day mortality: there were no events on 1766 procedures. The overall relative risk showed that the postoperative complication rate was higher in segmentectomy compared to lobectomy, without statistical significance. CONCLUSIONS: Our results suggest that segmentectomy might be a useful alternative to lobectomy for stage I NSCLC up to 2 cm. However, this appears to be time-dependent; in fact, the risk ratio for overall mortality becomes unfavorable for segmentectomy starting at 40 months after surgery. This last observation, together with some still undefined questions (solid/non-solid ratio, depth of the lesion, modest functional savings, etc.), leave room for further investigations on the real oncological effectiveness of segmentectomy.

Brixia system of screws: a titanium modular system with wide applicability for reinforced sternal closure in cardiac and thoracic surgery.

The use of cannulated screws and titanium plates to reinforce the sternal closure or to treat sternal dehiscence after median sternotomy has already been suggested in several articles. The system proposed here has some important advantages over those already described. Moreover, thanks to its characteristics, this system can also be used to treat pathologies affecting the entire rib cage. The system consists of a first threaded cannulated screw that is inserted in the bone or chondral cartilage and accommodates a cap screw that is tightened into the first screw and fixes a plate according to the following scheme: a threaded cannulated screw/plate/cap screw (Brixia system of screws). This system allows the plates to be fixed on the anterior face of the ribs and/or sternum without the need to enlarge dissection of the tissue, thereby lowering the danger of haemorrhage and injury to the thoracic organs. For this reason, it is particularly suitable for treating post-sternotomy sternal dehiscence, but it can be used to reinforce the primary sternal closure (after median or transversal sternotomy) in high-risk patients with sternal dehiscence. Owing to the modular nature of the system, singular components can also be utilized independently.

Pulmonary Lobectomy for Early-Stage Lung Cancer with Uniportal versus Three-Portal Video-Assisted Thoracic Surgery: Results from a Single-Centre Randomized Clinical Trial.

Video-assisted thoracic surgery (VATS) is a consolidated approach; however, there is no consensus on the number of ports leading to less postoperative pain. We compared early postoperative pain after uniportal and three-portal VATS lobectomy for early-stage NSCLC. In this randomized clinical trial, patients undergoing VATS lobectomy were randomly assigned to receive uniportal (U-VATS Group) or three-portal (T-VATS Group) VATS. The inclusion criteria were age ≤ 80 years and ASA < 4. The exclusion criteria were clinical T3, previous thoracic surgery, induction therapy, chest radiotherapy, connective tissue or vascular diseases, major organ failure, and analgesics or corticosteroids use. The postoperative analgesia protocol was based on NRS. Pain was measured as analgesic consumption; the secondary endpoints were intra- and postoperative complications, conversion rate, surgical time, dissected lymph nodes, hospital stay, and respiratory function. Out of 302 eligible patients, 120 were included; demographics were distributed homogeneously. The mean cumulative morphine consumption (CMC) in the U-VATS Group after 7 days was lower than in the T-VATS Group (77.4 mg vs. 90.1 mg, p = 0.003). Intraoperative variables and postoperative complications were comparable. The 30-day intercostal neuralgia rate was lower in the U-VATS Group, without reaching statistical significance. Patients undergoing U-VATS showed a lower analgesic consumption compared with the T-VATS Group; analgesic consumption was moderate in both groups.

Branching patterns and variations of the bronchus and blood vessels in the superior segment of the right lower lobe: a three-dimensional computed tomographic bronchography and angiography study.

Background: Superior segmentectomy is classified as simple due to the single intersegmental plane between the superior and basal segments. However, oncological outcomes in patients undergoing superior segmentectomy tend to be worse compared to those receiving other segmentectomy. The aim of this study is to determine the branching patterns and variations of the bronchus and blood vessels of the superior segment of the right lower lobe (RS6). Methods: Three-dimensional computed tomographic bronchography and angiography (3D-CTBA) was reconstructed in 316 patients who underwent enhanced chest computed tomography (CT) and subsequent surgery in our center from November 2018 to March 2021. Results: The bronchus in RS6 consisted of a single stem in 96.5% cases (305/316), and 2 separate stems in the remaining 3.5% cases (11/316). The artery in RS6 consisted of a single stem in 59.5% cases (188/316), 2 separate stems in 37.0% cases (117/316), and 3 separate stems in the remaining 3.5% cases (11/316). The vein in RS6 consisted of a single stem in 94.3% cases (298/316) and 2 separate stems in the remaining 5.7% cases (18/316). B6 variation was noted in 1.6% cases (5/316). A6 variation was noted in 18.0% cases (57/316), including the following: (I) coexistence of A6 and A2 (n=25); (II) A6b originating from A9+10/A10 alone (n=20); (III) A6c originating from A9+10 (n=10); and (IV) co-draining of A6 and A7 (n=2). V6 variation was noted in 11.7% cases (37/316), including the following: (I) co-draining of V6 and V2 (n=20); (II) co-draining of V6 and V4 (n=5); (III) V6 and V8+9 co-draining (n=3); (IV) V6 draining into the superior pulmonary vein (n=4); and (V) direct V6 draining into the left atrium (n=5). Conclusions: Variation of A6 and V6 in RS6 is much more common than previously reported. 3D-CTBA reconstruction is useful for pre-surgery planning.

Liquid biopsy in non-small cell lung cancer: a meta-analysis of state-of-the-art and future perspectives.

Introduction: To date, tissue biopsy represents the gold standard for characterizing non-small-cell lung cancer (NSCLC), however, the complex architecture of the disease has introduced the need for new investigative approaches, such as liquid biopsy. Indeed, DNA analyzed in liquid biopsy is much more representative of tumour heterogeneity. Materials and methods: We performed a meta-analysis of 17 selected papers, to attest to the diagnostic performance of liquid biopsy in identifying EGFR mutations in NSCLC. Results: In the overall studies, we found a sensitivity of 0.59, specificity of 0.96 and diagnostic odds ratio of 24,69. Since we noticed a high heterogeneity among different papers, we also performed the meta-analysis in separate subsets of papers, divided by 1) stage of disease, 2) experimental design and 3) method of mutation detection. Liquid biopsy has the highest sensitivity/specificity in high-stage tumours, and prospective studies are more reliable than retrospective ones in terms of sensitivity and specificity, both NGS and PCR-based techniques can be used to detect tumour DNA in liquid biopsy. Discussion: Overall, liquid biopsy has the potential to help the management of NSCLC, but at present the non-homogeneous literature data, lack of optimal detection methods, together with relatively high costs make its applicability in routine diagnostics still challenging.