Implementation of Artificial Intelligence in Personalized Prognostic Assessment of Lung Cancer: A Narrative Review.

Artificial Intelligence (AI) has revolutionized the management of non-small-cell lung cancer (NSCLC) by enhancing different aspects, including staging, prognosis assessment, treatment prediction, response evaluation, recurrence/prognosis prediction, and personalized prognostic assessment. AI algorithms may accurately classify NSCLC stages using machine learning techniques and deep imaging data analysis. This could potentially improve precision and efficiency in staging, facilitating personalized treatment decisions. Furthermore, there are data suggesting the potential application of AI-based models in predicting prognosis in terms of survival rates and disease progression by integrating clinical, imaging and molecular data. In the present narrative review, we will analyze the preliminary studies reporting on how AI algorithms could predict responses to various treatment modalities, such as surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. There is robust evidence suggesting that AI also plays a crucial role in predicting the likelihood of tumor recurrence after surgery and the pattern of failure, which has significant implications for tailoring adjuvant treatments. The successful implementation of AI in personalized prognostic assessment requires the integration of different data sources, including clinical, molecular, and imaging data. Machine learning (ML) and deep learning (DL) techniques enable AI models to analyze these data and generate personalized prognostic predictions, allowing for a precise and individualized approach to patient care. However, challenges relating to data quality, interpretability, and the ability of AI models to generalize need to be addressed. Collaboration among clinicians, data scientists, and regulators is critical for the responsible implementation of AI and for maximizing its benefits in providing a more personalized prognostic assessment. Continued research, validation, and collaboration are essential to fully exploit the potential of AI in NSCLC management and improve patient outcomes. Herein, we have summarized the state of the art of applications of AI in lung cancer for predicting staging, prognosis, and pattern of recurrence after treatment in order to provide to the readers a large comprehensive overview of this challenging issue.

Uniportal Video-Assisted Thoracoscopic Surgery Completion Lobectomy Long after Wedge Resection or Segmentectomy in the Same Lobe: A Bicenter Study.

BACKGROUND: Completion lobectomy (CL) following a prior resection in the same lobe may be complicated by severe pleural or hilar adhesions. The role of uniportal video-assisted thoracoscopic surgery (U-VATS) has never been evaluated in this setting. METHODS: Data were collected from two Italian centers. Between 2015 and 2022, 122 patients (60 men and 62 women, median age 67.7 ± 8.913) underwent U-VATS CL at least 4 weeks after previous lung surgery. RESULTS: Twenty-eight (22.9%) patients were affected by chronic obstructive pulmonary disease (COPD) and twenty-five (20.4%) were active smokers. Among the cohort, the initial surgery was performed using U-VATS in 103 (84.4%) patients, triportal-VATS in 8 (6.6%), and thoracotomy in 11 (9.0%). Anatomical segmentectomy was the initial surgery in 46 (37.7%) patients, while hilar lymphadenectomy was performed in 16 (13.1%) cases. CL was performed on 110 (90.2%) patients, segmentectomy on 10 (8.2%), and completion pneumonectomy on 2 (1.6%). Upon reoperation, moderate pleural adhesions were observed in 38 (31.1%) patients, with 2 (1.6%) exhibiting strong adhesions. Moderate hilar adhesions were found in 18 (14.8%) patients and strong adhesions in 11 (9.0%). The median operative time was 203.93 ± 74.4 min. In four (3.3%) patients, PA taping was performed. One patient experienced intraoperative bleeding that did not require conversion to thoracotomy. Conversion to thoracotomy was necessary in three (2.5%) patients. The median postoperative drainage stay and postoperative hospital stay were 5.67 ± 4.44 and 5.52 ± 2.66 days, respectively. Postoperative complications occurred in 34 (27.9%) patients. Thirty-day mortality was null. Histology was the only factor found to negatively influence intraoperative outcomes (p = 0.000). Factors identified as negatively impacting postoperative outcomes at univariate analyses were male sex (p = 0.003), age > 60 years (p = 0.003), COPD (p = 0.014), previous thoracotomy (p = 0.000), previous S2 segmentectomy (p = 0.001), previous S8 segmentectomy (p = 0.008), and interval between operations > 5 weeks (p= 0.005). In multivariate analysis, only COPD confirmed its role as an independent risk factor for postoperative complications (HR: 5.12, 95% CI (1.07-24.50), p = 0.04). CONCLUSIONS: U-VATS CL seems feasible and safe after wedge resection and anatomical segmentectomy.

Survival Outcome After Surgery in Patients With Thymoma Distant Recurrence.

OBJECTIVE: The aim of this study is to describe characteristics and survival outcome of patients who underwent surgical treatment for distant thymoma relapse according to the definition of the International Thymic Malignancy Interest Group. METHODS: Data of patients affected by thymoma recurrence from four different institutions were collected and retrospectively reviewed. Patients with locoregional metastases who underwent nonsurgical therapies and with incomplete data on follow-up were excluded. According to the International Thymic Malignancy Interest Group distant recurrence definition, patients with recurrence due to hematogenic localization were included. Clinical and pathologic characteristics were described using descriptive statistics, whereas survival outcome was calculated using Kaplan-Meier curves and Cox regression analysis. RESULTS: The analysis was conducted on 40 patients. A single localization was present in 13 patients, the relapse was intrathoracic in 28 cases (70%), and lung involvement was found in 26 cases. The liver was operated in seven cases, whereas other kinds of abdominal involvement were detected in eight cases. Adjuvant treatment was administered in 22 cases (55%).Five- and 10-year overall survival (OS) were 67% and 30%, respectively. Univariable analysis identified as significant favorable factor a low-grade histology (A, B1, B2): five-year OS at 92.3% versus 53.3% in high-grade (B3-C) (p = 0.035). Site of recurrence and number of localization did not influence the prognosis, but in patients with adjuvant therapy administration, there was a survival advantage also if not statistically significant: five-year OS 84.8% versus 54.5% in patients without adjuvant therapy (p = 0.101).Multivariable analysis confirmed as independent prognostic factor low-grade histology: hazard ratio = 0.176, 95% confidence interval 0.042-0.744, p = 0.018. CONCLUSIONS: Our study revealed a good survival outcome in patients who underwent surgery for distant thymoma recurrence, independently from the number and site of the relapse localization. Patients with A, B1, or B2 histology presented a significantly better survival than patients with B3-C.

The Prognostic Role of the Number of Involved Structures in Thymic Epithelial Tumors: Results from the ESTS Database.

BACKGROUND: The role of the number of involved structures (NIS) in thymic epithelial tumors (TETs) has been investigated for inclusion in future staging systems, but large cohort results still are missing. This study aimed to analyze the prognostic role of NIS for patients included in the European Society of Thoracic Surgeons (ESTS) thymic database who underwent surgical resection. METHODS: Clinical and pathologic data of patients from the ESTS thymic database who underwent surgery for TET from January 2000 to July 2019 with infiltration of surrounding structures were reviewed and analyzed. Patients' clinical data, tumor characteristics, and NIS were collected and correlated with CSS using Kaplan-Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using logistic regression analysis. RESULTS: The final analysis was performed on 303 patients. Histology showed thymoma for 216 patients (71.3%) and NET/thymic carcinoma [TC]) for 87 patients (28.7%). The most frequently infiltrated structures were the pleura (198 cases, 65.3%) and the pericardium in (185 cases, 61.1%), whereas lung was involved in 96 cases (31.7%), great vessels in 74 cases (24.4%), and the phrenic nerve in 31 cases (10.2%). Multiple structures (range, 2-7) were involved in 183 cases (60.4%). Recurrence resulted in the death of 46 patients. The CSS mortality rate was 89% at 5 years and 82% at 10 years. In the univariable analysis, the favorable prognostic factors were neoadjuvant therapy, Masaoka stage 3, absence of metastases, absence of myasthenia gravis, complete resection, thymoma histology, and no more than two NIS. Patients with more than two NIS presented with a significantly worse CSS than patients with no more than two NIS (CSS 5- and 10-year rates: 9.5% and 83.5% vs 93.2% and 91.2%, respectively; p = 0.04). The negative independent prognostic factors confirmed by the multivariable analysis were incomplete resection (hazard ratio [HR] 2.543; 95% confidence interval [CI] 1.010-6.407; p = 0.048) and more than two NIS (HR 1.395; 95% CI 1.021-1.905; p = 0.036). CONCLUSIONS: The study showed that more than two involved structures are a negative independent prognostic factor in infiltrative thymic epithelial tumors that could be used for prognostic stratification.

Surgeon experience influence lymphadenectomy during VATS lobectomy: National VATS database results.

OBJECTIVES: Aim of this study is to identify the factors that may influence the lymphadenectomy during VATS anatomical lung resection with particular interest on operator experience. MATERIALS AND METHODS: Clinical and pathological data from the prospective VATS Italian nationwide registry were reviewed and analysed. Patients with incomplete data regarding tumor and surgical characteristics, GGO, or with distant metastases were excluded. Patients clinical data, tumor characteristics, operation information and surgeon experience were collected and compared to resected lymph nodes number (#RN), resected N2 nodes number (#N2RN) and resected N2 stations number. A multivariable model was built using logistic regression analysis. Surgeon experience was categorized considering the number of VATS major anatomical resection and years after residency. RESULTS: The final analysis was conducted on 3727 patients. The median #RN and #N2RN were 11 (1-51) and 5 (0-41). Regarding the analysed outcomes, #N2RN > 6 resulted in 1812 (48.8%)cases, #RN > 10 in 2124 (57.0%)cases and more than 3 N2 stations were harvested in 1447 (38.8%)patients. First operator experience with number of VATS lobectomies>50 (p < 0.001), operator seniority after residency5-10years (p < 0.001), cTNM II/III(p = 0.017), lobectomy/bilobectomy vs segmentectomy (p < 0.001), and upper/middle lobe tumor location (p < 0.005)resulted significantly associated to #N2RN > 6 at the multivariable analysis. First operator experience with number of VATS lobectomies>50 (p < 0.001), operator seniority after residency5-10years (p < 0.001) and lobectomy/bilobectomy (p < 0.001) resulted significantly associated to #RN > 10 at the multivariable analysis. CONCLUSIONS: Our study showed that lymphadenectomy during VATS lobectomy is influenced by tumor factors such as cTstage and tumor location but also by operator experience, with a higher number of resected lymph nodes in surgeons with a high number of VATS procedures and years after residency compared to surgeons with less experience.

BRCA1-associated protein 1: Tumor predisposition syndrome and Kury-Isidor syndrome, from genotype-phenotype correlation to clinical management.

The BAP1 tumor suppressor gene encodes a deubiquitinase enzyme involved in several cellular activities, including DNA repair and apoptosis. Germline pathogenic variants in BAP1 have been associated with heritable conditions including BAP1 tumor predisposition syndrome 1 (BAP1-TPDS1) and a neurodevelopmental disorder known as Kury-Isidor syndrome (KURIS). Both these conditions are caused by monoallelic, dominant alterations of BAP1 but have never been reported in the same subject or family, suggesting a mutually exclusive genotype-phenotype correlation. This distinction is extremely important considering the early onset and aggressive nature of the types of cancer reported in individuals with TPDS1. Genetic counseling in subjects with germline BAP1 variants is fundamental to predicting the effect of the variant and the expected phenotype, assessing the potential risk of developing cancer for the tested subject and the family members who may carry the same variant and providing the multidisciplinary clinical team with the proper information to establish precise surveillance and management protocols.

Surgeon experience does not influence nodal upstaging during vats lobectomy: Results from a large prospective national database.

BACKGROUND: Despite recent improvement in preoperative staging, nodal and mediastinal upstaging occur in about 5% to 15% of cN0 patients. Different clinical and tumor characteristics are associated with upstaging, whereas the role of the surgeon's experience is not well evaluated. This study aimed to investigate if operator experience might influence nodal upstaging during video-assisted thoracic surgery anatomical lung resection. METHODS: Clinical and pathological data from the prospective video-assisted thoracic surgery Italian nationwide registry were reviewed and analyzed. Patients with incomplete data about tumor and surgical characteristics, ground glass opacities tumors, cN2 to 3, and M+ were excluded. Clinical data, tumor characteristics, and surgeon experience were correlated to nodal and mediastinal (N2) upstaging using Pearson's χ2 statistic or Fisher exact test for categorical variables and Mann-Whitney U and t tests for quantitative variables. A multivariable model was built using logistic regression analysis. Surgeon experience was categorized considering the number of video-assisted thoracic surgery major anatomical resections and years after residency. RESULTS: Final analysis was conducted on 3,319 cN0 patients for nodal upstaging and 3,471 cN0N1 patients for N2 upstaging. Clinical tumor-nodes-metastasis stage was stage I in 2,846 (81.9%) patients, stage II in 533 (15.3%), and stage III (cT3N1) in 92 (2.8%). Nodal upstaging occurred in 489 (13.1%) patients, whereas N2 upstaging occurred in 229 (6.1%) patients. Years after residency (P = .60 for nodal, P = .13 for N2 upstaging) and a number of video-assisted thoracic surgery procedures(P = .49 for nodal, P = .72 for nodal upstaging) did not correlate with upstaging. Multivariable analysis confirmed cT-dimension (P = .001), solid nodules (P < .001), clinical tumor-nodes-metastasis (P < .001) and maximum standardized uptake values (P < .001) as factors independently correlated to nodal upstaging, whereas cT-dimension (P = .005), clinical tumor-nodes-metastasis (P < .001) and maximum standardized uptake values (P = .028) resulted independently correlated to N2 upstaging. CONCLUSION: Our study showed that surgeon experience did not influence nodal and mediastinal upstaging during -assisted thoracic surgery anatomical resection, whereas cT-dimension, clinical tumor-nodes-metastasis, and maximum standardized uptake values resulted independently correlated to nodal and mediastinal upstaging.

The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review.

Background and Objective: Malignant pleural mesothelioma (MPM) is a very aggressive primary tumor of the pleura whose main risk factor is exposure to asbestos. However, only a minority of exposed people develops MPM and the incidence of MPM cases without an apparent association with asbestos exposure has been increasing in recent years, suggesting that genetic predisposing factors may play a crucial role. In addition, several studies reported familial cases of MPM, suggesting that heredity may be an important and underestimated feature in MPM development. Several candidate genes have been associated with a predisposition to MPM and most of them play a role in DNA repair mechanisms: overall, approximately 20% of MPM cases may be related to genetic predisposition. A particular category of patients with high susceptibility to MPM is represented by carriers of pathogenic variants in the BAP1 gene. Germline variants in BAP1 predispose to the development of MPM following an autosomal dominant pattern of inheritance in the familial cases. MPMs in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. In the present narrative review, we presented a comprehensive overview of genetic susceptibility in the development of MPM. Methods: The narrative review is based on a selective literature carried out in PubMed in 2023. Inclusion criteria were original articles in English language, and clinical trials (randomized, prospective, or retrospective). Key Content and Findings: We summarized the somatic and germline variants and the differences in terms of clinicopathological features and prognosis between gene-related MPM (GR-MPM) and asbestos-related MPM (AR-MPM). We also discussed the indications for screening, genetic testing, and surveillance of patients with BAP1 germline variants. Conclusions: In this narrative review, we have emphasized that the BAP1 gene's harmful germline variations are inherited in an autosomal dominant manner in familial cases. MPMs in individuals with these variations are less severe, and their medical care necessitates a collaborative effort. Additionally, we have outlined the current therapeutic prospects for MPM, including the possibility of gene-specific therapy, which is currently promising but still requires clinical validation.

The Role of Human Papilloma Virus (HPV) in Primary Lung Cancer Development: State of the Art and Future Perspectives.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Notably, the incidence of lung cancer among never-smokers, predominantly women, has been rising in recent years. Among the various implicated risk factors, human papilloma virus (HPV) may play a role in the development of NSCLC in a certain subset of patients. The prevalence of high-risk HPV-DNA within human neoplastic lung cells varies across the world; however, the carcinogenetic role of HPV in NSCLC has not been completely understood. Bloodstream could be one of the routes of transmission from infected sites to the lungs, along with oral (through unprotected oral sex) and airborne transmission. Previous studies reported an elevated risk of NSCLC in patients with prior HPV-related tumors, such as cervical, laryngeal, or oropharyngeal cancer, with better prognosis for HPV-positive lung cancers compared to negative forms. On the other hand, 16% of NSCLC patients present circulating HPV-DNA in peripheral blood along with miRNAs expression. Typically, these patients have a poorly differentiated NSCLC, often diagnosed at an advanced stage. However, HPV-positive lung cancers seem to have a better response to target therapies (EGFR) and immune checkpoint inhibitors and show an increased sensitivity to platinum-based treatments. This review summarizes the current evidence regarding the role of HPV in NSCLC development, especially among patients with a history of HPV-related cancers. It also examines the diagnostic and prognostic significance of HPV, investigating new future perspectives to enhance cancer screening, diagnostic protocols, and the development of more targeted therapies tailored to specific cohorts of NSCLC patients with confirmed HPV infection.

Are the Efficacy and Safety of Chest Tubes in Uniportal Video-Assisted Thoracic Surgery Related to the Level of Intercostal Space Insertion or to the Drain Type? A Prospective Multicenter Study.

OBJECTIVES: The aim of this study is to evaluate if the efficacy and safety of chest tube placement are influenced by the level of intercostal space insertion (uniportal VATS vs. biportal VATS) or by the type of drain employed (standard vs. smart coaxial drain). METHODS: Data on patients who underwent either uniportal or biportal VATS upper lobectomies with lymphadenectomy were prospectively collected in three European centers. The uniportal VATS group with a 28 Fr standard chest tube (U-VATS standard) was compared with the uniportal VATS group with a 28 Fr smart drain (U-VATS smart), and U-VATS smart was also compared with biportal VATS with a 28 Fr smart drain inserted in the VIII intercostal space (Bi-VATS smart). RESULTS: When comparing the U-VATS standard group with the U-VATS smart, a higher fluid output was recorded in the U-VATS smart (p: 0.004) in the III post-operative day (p.o.) and overall (p: 0.027), with a lower 90-day re-admission in the U-VATS smart (p: 0.04). The Bi-VATS smart group compared to U-VATS smart showed a higher fluid output in the I p.o. (p < 0.001), with no difference in total fluid amount or hospitalization. The Bi-VATS smart recorded a lower incidence (p < 0.001) of residual pleural space or effusion (p: 0.004) at chest X-rays prior to drain removal but a higher level of pain and chronic intercostal neuralgia (p: 0.03). CONCLUSIONS: Chest tube insertion through the same incision space in uniportal VATS seems to be safe and effective. Smart drains can improve the fluid output in uniportal VATS, as if the drainage were inserted in a lower space (i.e., biportal VATS), but with less discomfort.

The Efficacy of Continuous Serratus Anterior and Erector Spinae Plane Blocks vs Intercostal Nerve Block in Uniportal-Vats Surgery: A Propensity-Matched Prospective Trial.

BACKGROUND: To evaluate the analgesic efficacy of continuous erector spinae plane block(c-ESPB) and serratus anterior plane block(c-SAPB) versus the intercostal nerve block (ICNB) in Uniportal-VATS in terms of pain control, drug consumption, and complications. METHODS: Ninety-three consecutive patients, undergone one of the three peripheral nerve blocks after Uniportal-VATS, were prospectively enrolled. A 1:1 propensity score matching was used to minimize bias. RESULTS: C-ESPB and c-SAPB groups had no difference in morphine request upon awakening compared to ICNB. A higher VAS-score was recorded in c-ESPB compared to ICNB in the first 12 h after surgery. A significantly lower consumption of paracetamol in II postoperative day (p.o.d.) and tramadol in I and II p.o.d. was recorded in the c-ESPB group compared to the ICNB group. A higher dynamic VAS score was recorded at 24 h and 48 h in the ICNB group compared to the c-SAPB. No difference was found in safety, VAS-score and drug consumption between c-ESPB and c-SAPB at any given time, except for a higher tramadol request in c-SAPB in II p.o.d. CONCLUSIONS: C-ESPB and c-SAPB appear to have the same safety and analgesic efficacy when compared between them and to ICNB in Uniportal-VATS approach. C-ESPB showed a delayed onset of analgesic effect and a lower postoperative drug consumption compared to ICNB.

Unsolved Issues in Thymic Epithelial Tumour Stage Classification: The Role of Tumour Dimension.

According to the different classifications now in use, thymic tumours are staged by the extent of local invasiveness, and tumour size is not included as a major determinant for the T category. The aim of this double-site retrospective study is to analyse the correlation between tumour dimension and overall survival (OS) in patients who underwent surgical treatment. From January 2000 to December 2020, patients with thymic epithelial tumours who underwent surgical resection were included in this study. Data from a total of 332 patients were analysed. Five- and ten-year overall survival (5-10 YOS) was 89.26% and 87.08%, respectively, while five- and ten-year disease-free survival (DFS) was 88.12% and 84.2%, respectively. Univariate analysis showed a significant correlation between male sex (p-value 0.02), older age (p-value < 0.01), absence of myasthenia gravis (p-value < 0.01), increase in pTNM (pathological Tumor Node Metastasis) (p-value 0.03) and increase in the number of infiltrated organs (p-value 0.02) with an increase in tumour dimension. Tumour dimension alone was not effective in the prediction of DFS and OS, both when considered as a continuous variable and when considered with a cut-off of 3 and 5 cm. However, with multivariate analysis, it was effective in predicting OS in the aforementioned conditions (p-value < 0.01). Moreover, multivariate analysis was also used in the thymoma and Masaoka I subgroups. In our experience, the role of tumour dimension as a descriptor of the T parameter of the TNM (Tumor Node Metastasis) staging system seemed to be useful in improving this system.

Surgery for Non-Small Cell Lung Cancer in the Personalized Therapy Era.

Lung cancer remains one of the tumours with the highest incidence and the poorestprognosis, with an estimated incidence of more than 220,000 cases with 135,000 cancerrelateddeaths annually in the United States [1,2].[...].

Non-Small Cell Lung Cancer With N1 Involvement or Skip Metastases Presents the Same Survival Outcome: Results From a Multicentric Study.

BACKGROUND: The prognostic difference among patients affected by NSCLC with hilar metastases only or mediastinal nodes metastases without hilar involvement (skip metastases) is still unclear. Aim of this study is to analyse if prognostic difference are present or if the two groups present the same survival outcome. MATERIALS AND METHODS: Data on NSCLC patients from 7 high volume centres (2004-2014) were collected and retrospectively reviewed. Histology different from adenocarcinoma(ADC) or squamous cell carcinoma(SCC), patients without data on lymphadenectomy, who underwent neoadjuvant treatment, with distant metastases or incomplete resection were excluded, selecting patients with hilar involvement or with skip metastases. Different prognostic factors such as Tstage, histology, pathological stage, nodal characteristics and adjuvant therapy administration were correlated to overall survival (OS) by the Kaplan-Meier product-limit method. The log-rank test was used to assess differences between subgroups. A multivariable Cox proportional hazard model was developed using stepwise regression to compare the prognostic power of different factors. RESULTS: The final analysis was conducted on 480 adenocarcinoma/squamous cell carcinoma patients. Five-year OS (5YOS) resulted 53.9%. No significant differences in OS were detected comparing pN1 vs. pN2 patients or stage IIB vs. stage IIIA-B patients. Univariable confirmed as favourable prognostic factors young age (P<.001), T1-2 tumors (P=.030), number of resected nodes≥10 (P=.040), lymph node ratio (P=.026). Multivariable analysis confirmed as independent negative prognostic factors T≥3 (HR:1.385, 95%CI:1.037-1.851, P=.027) and age≥68 years (HR1.637, 95%CI:1.245-2.152). CONCLUSION: Patients with N1 involvement or skip metastases present a similar prognosis, suggesting that N2 involvement in these cases may be related to a direct lymphatic drainage to the mediastinal stations.

Reducing Post-Operative Alveolo-Pleural Fistula by Applying PGA-Sheets (Neoveil) after Major Lung Resection: A Historical Case-Control Study.

Alveolo-pleural fistula remains a serious post-operative complication in lung cancer patients after surgery, which is associated with prolonged hospital stay and higher healthcare costs. The aim of this study is to evaluate the efficacy of a polyglycol acid (PGA)-sheet known as Neoveil in preventing post-operative air-leak in cases of detected intra-operative air-leak after lung resection. Between 11/2021 and 7/2022, a total of 329 non-small cell lung cancer (NSCLC) patients were surgically treated in two institutions. Major lung resections were performed in 251 cases. Among them, 44 patients with significant intra-operative air-leak at surgery were treated by reinforcing staple lines with Neoveil (study group). On the other hand, a historical group (selected by propensity score matched analysis) consisting of 44 lung cancer patients with significant intra-operative air leak treated by methods other than the application of sealant patches were considered as the control group. The presence of prolonged air-leak (primary endpoint), pleural drainage duration, hospital stay, and post-operative complication rates were evaluated. The results showed that prolonged air-leak (>5 days after surgery) was not observed in study group, while this event occurred in four patients (9.1%) in the control group. Additionally, a substantial reduction (despite not statistically significant) in the chest tube removal was noted in the study group with respect to the control group (3.5 vs. 4.5, p = 0.189). In addition, a significant decrease in hospital stay (4 vs. 6 days, p = 0.045) and a reduction in post-operative complications (2 vs. 10, p = 0.015) were observed in the study group when compared with the control group. Therefore, in cases associated with intra-operative air-leak after major lung resection, Neoveil was considered a safer and more effective aerostatic tool and represents a viable option during surgical procedures.