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.

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.

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.

Lung Adenocarcinoma Diagnosed at a Younger Age Is Associated with Advanced Stage, Female Sex, and Ever-Smoker Status, in Patients Treated with Lung Resection.

To date, the factors which affect the age at diagnosis of lung adenocarcinoma are not fully understood. In our study, we examined the relationships of age at diagnosis with smoking, pathological stage, sex, and year of diagnosis in a discovery (n = 1694) and validation (n = 1384) series of lung adenocarcinoma patients who had undergone pulmonary resection at hospitals in the Milan area and at Thoraxklinik (Heidelberg), respectively. In the discovery series, younger age at diagnosis was associated with ever-smoker status (OR = 1.5, p = 0.0035) and advanced stage (taking stage I as reference: stage III OR = 1.4, p = 0.0067; stage IV OR = 1.7, p = 0.0080), whereas older age at diagnosis was associated with male sex (OR = 0.57, p < 0.001). Analysis in the validation series confirmed the ever versus never smokers' association (OR = 2.9, p < 0.001), the association with highest stages (stage III versus stage I OR = 1.4, p = 0.0066; stage IV versus stage I OR = 2.0, p = 0.0022), and the male versus female sex association (OR = 0.78, p = 0.032). These data suggest the role of smoking in affecting the natural history of the disease. Moreover, aggressive tumours seem to have shorter latency from initiation to clinical detection. Finally, younger age at diagnosis is associated with the female sex, suggesting that hormonal status of young women confers risk to develop lung adenocarcinoma. Overall, this study provided novel findings on the mechanisms underlying age at diagnosis of lung adenocarcinoma.

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.

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.

Comparison Between Electronic and Traditional Chest Drainage Systems: A Multicenter Randomized Study.

BACKGROUND: Air leak is the major factor that influences the permanence of the chest tube and the in-hospital length of stay (LOS) among patients undergoing lung resections. The aim of this study was to determine whether the use of digital chest drain systems, compared with traditional ones, reduced the duration of chest drainage and postoperative in-hospital LOS in patients undergoing video-assisted thoracoscopic (VATS) lobectomy. METHODS: The study was a prospective, randomized, multicenter trial. Patients undergoing VATS lobectomy were randomized in 2 groups, receiving a digital drain system or a traditional one and managed accordingly to the protocol. RESULTS: Among 503 patients who fulfilled inclusion criteria and were randomized, 38 dropped out after randomization. Finally, 465 patients were analyzed, of whom 204 used the digital device and 261 the traditional one. In the digital group, there was a significantly shorter median chest tube duration of 3 postoperative days (interquartile range [IQR], 2-4 days) vs 4 postoperative days (IQR, 3-4 days; P = .001) and postoperative in-hospital LOS of 4 days (IQR, 3-6 days) vs 5 days (IQR, 4-6 days; P = .035). Analysis of predictors for increased duration of air leaks showed a relationship with male sex (P = .039), forced expiratory volume in 1 second percentage (P = .004), forced vital capacity percentage (P = .03), and presence of air leaks at the end of surgery (P = .001). CONCLUSIONS: In patients undergoing VATS lobectomy, the use of a digital drainage system allows an earlier removal of the chest drain compared with the traditional system, leading to a shorter in-hospital LOS.

Advances in Lung Transplantation.

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

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.

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.

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.

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.

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.

Isolation and characterization of two newly established thymoma PDXs from two relapses of the same patient: a new tool to investigate thymic malignancies.

BACKGROUND: Thymic malignancies are a heterogeneous group of rare cancers for which systemic chemotherapy is the standard treatment in the setting of advanced, recurrent or refractory diseases. Both environmental and genetic risk factors have not been fully clarified and few target-specific drugs have been developed for thymic epithelial tumors. A major challenge in studying thymic epithelial tumors is the lack of preclinical models for translational studies. MAIN BODY: Starting from bioptic material of two consecutive recurrences of the same patient, we generated two patient-derived xenografts. The patient-derived xenografts models were characterized for histology by immunohistochemistry and mutations using next-generation sequencing. When compared to the original tumors resected from the patient, the two patient-derived xenografts had preserved morphology after the stain with hematoxylin and eosin, although there was a moderate degree of de-differentiation. From a molecular point of view, the two patient-derived xenografts maintained 74.3 and 61.8% of the mutations present in the human tumor of origin. SHORT CONCLUSION: The newly generated patient-derived xenografts recapitulate both the molecular characteristics and the evolution of the thymoma it derives from well, allowing to address open questions for this rare cancer.

Early psychological intervention in adult patients after hospitalization during COVID-19 pandemia. A single center observational study.

The coronavirus disease 2019 pandemic has represented an individual and collective trauma with an impact on mental health. COVID-19 survivors need to be screened for psychological distress regularly for timely intervention. After March 2020, an outpatients clinic for follow up of discharged COVID-19 patients was set up at Infectious Diseases Department of the Hospital of Lecco, Italy. Blood exams, specialistic visits were performed for each patients and IES-R and BDI scales were dispensed. 523 patients were referred to the clinic; 93 of them resulted positive at IES-R and/or BDI self-report and 58 agreed to have early interviews with psychologist specialist. Patients could receive only a short psychoeducation/psychological support intervention or in addition to the same, even a specific trauma-focused psychotherapeutic intervention with EMDR where clinically indicated. IES-R e BDI were administered pre- and post-intervention. The results show that the average of the post-traumatic stress scores detected at IES-R is above the clinical cut-off for the entire sample. There is an overall change in the decrease in mean scores on the IES and BDI scales before and after psychological intervention. Among the patients for whom psychopharmacological therapy was also necessary, those who had COVID-mourning in family improved the most at IES-R scale post- intervention. With respect to EMDR treatment, there is a significant improvement in depressive symptoms noticed at BDI for male patients who have received neither psychotropic drugs nor CPAP. Being hospitalized for coronavirus has a significant impact on the patient's mental health and it is a priority to arrange early screening to intercept psychological distress and give it an early response.

Prediction of Ablation Volume in Percutaneous Lung Microwave Ablation: A Single Centre Retrospective Study.

BACKGROUND: Percutaneous Microwave Ablation (MWA) of lung malignancies is a procedure with many technical challenges, among them the risk of residual disease. Recently, dedicated software able to predict the volume of the ablated area was introduced. Cone-beam computed tomography (CBCT) is the imaging guidance of choice for pulmonary ablation in our institution. The volumetric prediction software (VPS) has been installed and used in combination with CBCT to check the correct position of the device. Our study aimed to compare the results of MWA of pulmonary tumours performed using CBCT with and without VPS. METHODS: We retrospectively reviewed 1-month follow-up enhanced contrast-enhanced computed tomography (CECT) scans of 10 patients who underwent ablation with the assistance of VPS (group 1) and of 10 patients who were treated without the assistance of VPS (group 2). All patients were treated for curative purposes, the maximum axial diameter of lesions ranged between 5 and 22 mm in group 1 and between 5 and 25 mm in group 2. We compared the presence of residual disease between the two groups. RESULTS: In group 1 residual disease was seen in only 1 patient (10%) in which VPS had ensured complete coverage of the tumour. In group 2 residual disease was found in 3 patients (30%). CONCLUSIONS: Using this software during MWA of lung malignancies could improve the efficacy of the treatment compared to the conventional only CBCT guidance.

Nonintubated versus intubated thoracoscopic bullectomy for primary spontaneous pneumothorax: A multicenter propensity-matched analysis.

BACKGROUND: We aimed at comparing in a multicenter propensity-matched analysis, results of nonintubated versus intubated video-assisted thoracic surgery (VATS) bullectomy/blebectomy for primary spontaneous pneumothorax (PSP). METHODS: Eleven Institutions participated in the study. A total of 208 patients underwent VATS bullectomy by intubated (IVATS) (N = 138) or nonintubated (NIVATS) (N = 70) anesthesia during 60 months. After propensity matching, 70 pairs of patients were compared. Anesthesia in NIVATS included intercostal (N = 61), paravertebral (N = 5) or thoracic epidural (N = 4) block and sedation with (N = 24) or without (N = 46) laryngeal mask under spontaneous ventilation. In the IVATS group, all patients underwent double-lumen-intubation and mechanical ventilation. Primary outcomes were morbidity and recurrence rates. RESULTS: There was no difference in age (26.7 ± 8 vs 27.4 ± 9 years), body mass index (19.7 ± 2.6 vs 20.6 ± 2.5), and American Society of Anesthesiology score (2 vs 2). Main results show no difference both in morbidity (11.4% vs 12.8%; p = 0.79) and recurrence free rates (92.3% vs 91.4%; p = 0.49) between NIVATS and IVATS, respectively, whereas a difference favoring the NIVATS group was found in anesthesia time (p < 0.0001) and operative time (p < 0.0001), drainage time (p = 0.001), and hospital stay (p < 0.0001). There was no conversion to thoracotomy and no hospital mortality. One patient in the NIVATS group needed reoperation due to chest wall bleeding. CONCLUSION: Results of this multicenter propensity-matched study have shown no intergroup difference in morbidity and recurrence rates whereas shorter operation room time and hospital stay favored the NIVATS group, suggesting a potential increase in the role of NIVATS in surgical management of PSP. Further prospective studies are warranted.