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.

Multimodal therapy for synchronous bone oligometastatic NSCLC: The role of surgery.

OBJECTIVES: The study aimed to assess the feasibility of radical surgical treatment for selected bone-oligometastatic non-small cell lung cancer (NSCLC) patients and to identify prognostic factors associated with survival. MATERIALS AND METHODS: The clinical records of 27 patients with bone synchronous oligometastatic NSCLC were retrospectively analyzed. RESULTS: Thirteen (48.1%) bone metastases were treated by surgery and 14 (51.9%) by local radiotherapy. Eighteen (66.7%) patients underwent induction chemotherapy before lung surgery, and 3 (11.1%) concurrent radiotherapy. Pulmonary surgery was a major lung resection in 23 (85.2%) cases. Intraoperative and 30-days mortality was null. Only one major (ARDS) and 10 (37.04%) mild complications (like air leakage, arrhythmia, and mucus retention) were recorded. 1-year and 5-years OS from the diagnosis and 1-year, 3- years disease-free survival (DFS) were 96%, 38%, and 66%, 30%, respectively. After stepwise Cox regression analysis, local recurrence (p = 0.05) and metachronous metastases (p = 0.04) maintained their independent prognostic value as overall survival negative determinants. Nodal upstaging (p = 0.04) and nonsurgical treatment of bone lesion (p = 0.03) turned out to be independent risk factors for shorter DFS; the vertebral localization of bone metastases showed only a remarkable trend towards significance (p = 0.06) as a risk factor for a worse DFS. CONCLUSIONS: In selected patients, surgical treatment of primary NSCLC and bone synchronous metastasis seems to be safe and feasible and rewarding survivals may be expected.

Role of Peripheral Blood Markers for Detecting Response and Predicting Prognosis in Patients with Non-small-cell Lung Cancer Undergoing Neoadjuvant Therapy and Surgery.

INTRODUCTION: To date, no validated predictors of response before neoadjuvant therapy (NAD) are currently available in locally advanced non-small-cell lung cancer (NSCLC). In this study, different peripheral blood markers were investigated before NAD (pre-NAD) and after NAD/before surgery (post-NAD) to evaluate their influence on the treatment outcomes. METHODS: Patients affected by locally advanced NSCLC (cT1-T4/N0-2/M0) who underwent NAD followed by surgery from January 1996 to December 2019 were considered for this retrospective analysis. The impact of peripheral blood markers on downstaging post-NAD and on overall survival (OS) was evaluated using multivariate logistic and Cox regression models. Time to event analysis was performed by means of Kaplan-Meier survival curves and Log Rank tests at 5 years from surgery. RESULTS: Two hundred and seventy-two consecutive patients were included. Most of the patients had Stage III NSCLC (83.5%). N2 disease was reported in 188 (69.1%) patients. Surgical resection was performed in patients with stable disease or downstaging post-NAD. Nodal downstaging was observed in 80% of clinical N2 (cN2) patients. The median follow-up of the total series was 74 months (range 6-302). Five-year OS in the overall population and in N2 population was 74.6% and 73.5%, respectively. The pre-surgery platelets level (PLT) (p = 0.019) and the variation (pre-NAD/post-NAD) of the neutrophil/lymphocyte ratio (p = 0.024) were identified as independent prognostic factors of OS. The preoperative PLT value (p value = 0.031) was confirmed as the only predictor of NAD response. CONCLUSIONS: The clinical role of peripheral blood markers in locally advanced NSCLC needs to be further investigated. Based on these preliminary results, these factors may be used as auxiliary markers for the prediction of response to neoadjuvant treatment and as prognostic factors for stratification in multimodal approaches.

Exploring technical issues in personalized medicine: NSCLC survival prediction by quantitative image analysis-usefulness of density correction of volumetric CT data.

The aim of this study was to apply density correction method to the quantitative image analysis of non-small cell lung cancer (NSCLC) computed tomography (CT) images, determining its influence on overall survival (OS) prediction of surgically treated patients. Clinicopathological (CP) data and preoperative CT scans, pre- and post-contrast medium (CM) administration, of 57 surgically treated NSCLC patients, were retrospectively collected. After CT volumetric density measurement of primary gross tumour volume (GTV), aorta and tracheal air, density correction was conducted on GTV (reference values: aortic blood and tracheal air). For each resulting data set (combining CM administration and normalization), first-order statistical and textural features were extracted. CP and imaging data were correlated with patients 1-, 3- and 5-year OS, alone and combined (uni-/multivariate logistic regression and Akaike information criterion). Predictive performance was evaluated using the ROC curves and AUC values and compared among non-normalized/normalized data sets (DeLong test). The best predictive values were obtained when combining CP and imaging parameters (AUC values: 1 year 0.72; 3 years 0.82; 5 years 0.78). After normalization resulted an improvement in predicting 1-year OS for some of the grey level size zonebased features (large zone low grey level emphasis) and for the combined CP-imaging model, a worse performance for grey level co-occurrence matrix (cluster prominence and shade) and first-order statistical (range) parameters for 1- and 5-year OS, respectively. The negative performance of cluster prominence in predicting 1-year OS was the only statistically significant result (p value 0.05). Density corrections of volumetric CT data showed an opposite influence on the performance of imaging quantitative features in predicting OS of surgically treated NSCLC patients, even if no statistically significant for almost all predictors.

Early nasal high-flow versus Venturi mask oxygen therapy after lung resection: a randomized trial.

BACKGROUND: Data on high-flow nasal oxygen after thoracic surgery are limited and confined to the comparison with low-flow oxygen. Different from low-flow oxygen, Venturi masks provide higher gas flow at a predetermined fraction of inspired oxygen (FiO2). We conducted a randomized trial to determine whether preemptive high-flow nasal oxygen reduces the incidence of postoperative hypoxemia after lung resection, as compared to Venturi mask oxygen therapy. METHODS: In this single-center, randomized trial conducted in a teaching hospital in Italy, consecutive adult patients undergoing thoracotomic lung resection, who were not on long-term oxygen therapy, were randomly assigned to receive high-flow nasal or Venturi mask oxygen after extubation continuously for two postoperative days. The primary outcome was the incidence of postoperative hypoxemia (i.e., ratio of the partial pressure of arterial oxygen to FiO2 (PaO2/FiO2) lower than 300 mmHg) within four postoperative days. RESULTS: Between September 2015 and April 2018, 96 patients were enrolled; 95 patients were analyzed (47 in high-flow group and 48 in Venturi mask group). In both groups, 38 patients (81% in the high-flow group and 79% in the Venturi mask group) developed postoperative hypoxemia, with an unadjusted odds ratio (OR) for the high-flow group of 1.11 [95% confidence interval (CI) 0.41-3] (p = 0.84). No inter-group differences were found in the degree of dyspnea nor in the proportion of patients needing oxygen therapy after treatment discontinuation (OR 1.34 [95% CI 0.60-3]), experiencing pulmonary complications (OR 1.29 [95% CI 0.51-3.25]) or requiring ventilatory support (OR 0.67 [95% CI 0.11-4.18]). Post hoc analyses revealed that PaO2/FiO2 during the study was not different between groups (p = 0.92), but patients receiving high-flow nasal oxygen had lower arterial pressure of carbon dioxide, with a mean inter-group difference of 2 mmHg [95% CI 0.5-3.4] (p = 0.009), and were burdened by a lower risk of postoperative hypercapnia (adjusted OR 0.18 [95% CI 0.06-0.54], p = 0.002). CONCLUSIONS: When compared to Venturi mask after thoracotomic lung resection, preemptive high-flow nasal oxygen did not reduce the incidence of postoperative hypoxemia nor improved other analyzed outcomes. Further adequately powered investigations in this setting are warranted to establish whether high-flow nasal oxygen may yield clinical benefit on carbon dioxide clearance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02544477 . Registered 9 September 2015.

Non-Small Cell Lung Cancer with Chest Wall Involvement: Integrated Treatment or Surgery Alone?

BACKGROUND: The aim of this study was to identify prognostic factors in patients affected by non-small cell lung cancer (NSCLC) with chest wall (CW) involvement, analyzing different strategies of treatment and surgical approaches. METHODS: Records of 59 patients affected by NSCLC with CW involvement underwent surgery were retrospectively reviewed, from January 2000 to March 2013. RESULTS: Induction therapy was administered to 18 (30.5%) patients while adjuvant treatment to 36 (61.0%). In 36 (61%) patients, lung resection was associated only with a parietal pleural resection while in 23 (39%) with CW en-bloc resection. Overall 5-year survival was 34%. Prognostic factors were evaluated in the 51 (86.4%) completely resected (R0) patients.Five-year survival was 60% in patients undergoing induction therapy followed by surgery and 24% in those who underwent surgery as first treatment (p = 0.11). Five-year survival was better in the neoadjuvant group than that in the surgery group in IIB (T3N0) p-stage (100 vs 28%, p = 0.03), while in the IIIA (T3N1-2,T4N0) p-stage it was of 25 vs 0%, respectively (p = 0.53).No 5-year survival difference was found in case of parietal pleural resection versus CW en-bloc resection (p = 0.27) and in case of only parietal pleural involvement versus soft tissue (p = 0.78).In case of incomplete resection (R1), patients undergoing adjuvant radiotherapy had better 2-year survival than patients untreated: 60% vs 0% (p = 0.025). CONCLUSIONS: Type of surgical resection and the deep of infiltration of disease do not influence survival in this subset of patients. Integrated treatments seem to be suitable: neoadjuvant therapies ensure a better survival rate than surgery alone in IIB and IIIA patients, instead adjuvant radiotherapy proves a fundamental option in incomplete resections.

Digital Devices Improve Chest Tube Management: Results from a Prospective Randomized Trial.

BACKGROUND: Digital devices could help clinical practice measuring the air leak, but their role is still debated. Aim of this study is to test advantages using these devices. METHODS: From June 2012 to May 2015, we enrolled 95 patients undergoing lobectomy or wedge resection in a prospective randomized trial. Patients were divided into two groups: group D (digital, 50 patients) evaluated with digital device and group E (empirical, 45 patients) evaluated with water seal. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to select and assess predictors of persistent air leak. In group D, chest drain was removed if the air leak was absent or < 0.5 L/h for 12 consecutive hours and in group E if clinical signs of air leak were absent. RESULTS: Mean hospitalization and mean chest tube stay was 6.0 ± 3.3 and 4.4 ± 3.2 days, respectively, prolonged air leak occurred in nine (8%). Hospitalization was 5.8 ± 2.5 versus 6.2 ± 4.2 days (p = 0.5), while mean chest tube stay was 4.1 ± 2.0 versus 4.6 ± 3.5 days (p = 0.4) in group D and group E, respectively. Clamping test was needed in one patient in group D and in seven in group E (p = 0.019). At multivariate analysis, heart disease (p < 0.0001), lobectomy (p < 0.0001), fused fissure (p < 0.0001), and air leakage in first postoperative (p.o.) day were predictors of persistent air leak (AUC on the ROC curve of 69.7%, sensibility: 77.8%). In group D, an air leak value > 0.2 L/h with spikes over 0.5 L/h in third p.o. was predictive of persistent air leak, with chest tube duration of 7.73 ± 5.20 versus 4.32 ± 1.33 days (AUC: 83%, sensitivity: 80%, p < 0.0001). CONCLUSION: In our experience, digital devices reduced observer variability and mistakes in chest tube management, thus identifying patients at risk for prolonged air leak.

Incidence and Management of Post-Lobectomy and Pneumonectomy Bronchopleural Fistula.

INTRODUCTION: Bronchopleural fistula is a rare but potentially fatal complication of pulmonary resections and proper management is essential for its resolution. In this study, we analyzed the incidence of fistula after pulmonary resection and reported data about endoscopic and conservative treatments of this complication. METHODS: From January 2003 to December 2013, 835 patients underwent anatomic lung resections: 786 (94.1 %) had a lobectomy and 49 (5.9 %) a pneumonectomy. Bronchopleural fistula was suspected by clinical signs and confirmed by endoscopic visualization. RESULTS: Eighteen patients (2.2 %) developed a bronchopleural fistula, 11 in lobectomy group (1.4 %) and 7 in pneumonectomy group (14.3 %). The fistula size ranged between <1 mm and 6 mm and mean time of fistula onset was 33.9 ± 54.9 days after surgery. Of 18 patients who developed fistula, one died due to acute respiratory failure and another one was reoperated and then died to causes unrelated to the treatment. All the remaining 16 patients were treated with a conservative therapy that consisted in keeping or replacing a drainage chest tube. Nine of them underwent also endoscopic closure of the fistula using biological or synthetic glues. The mean period of time elapsed for the resolution of this complication was shorter with combined (conservative + endoscopic) than with conservative treatment alone (15.4 ± 13.2 vs. 25.8 ± 13.2 days, respectively), but without significant difference between the two methods (p: 0.299). CONCLUSION: Endoscopic therapy, associated with a conservative treatment, is a safe and useful option in the management of the postoperative bronchopleural fistula.

Robotic surgery for thymic cysts: clinical features, management, and results of a multicentric study.

Thymic cysts are rare, radiological diagnosis is often incidental, and cysts seldom assume clinical relevance for symptoms of compression. Thymoma were occasionally found inside both complex and simple thymic cysts. Given the challenges in accurately clinical diagnosing and since the occasionally discovering of thymoma inside both complex and simple thymic cysts, the management of thymic cysts remains controversial. Advancements in surgical tools such as robotics, applied to thymic conditions, could potentially transform the approach to thymic cysts. We report one the largest multicentric series of thymic cysts surgically treated with robotic approach, focusing on preoperative findings and surgical results. Cases were gathered from three Italian thoracic surgery centers with homogeneous clinical practice, significant experience in thymic neoplasms, and thoracic robotic skilled. Surgical intervention was indicated for patients with radiological diagnosis of thymic cysts under the following circumstances: the presence of symptoms, concurrent myasthenia gravis, cysts growing in follow-up, and the complexity of the cyst with suspicion of neoplasm. Data were collected and matched according to postoperative and pathological features to identify potential prognostic factors. Population include 57 patients, 29/28 male/female ratio with mean age of 59.46 ± 11.67 years. The average size of the thymic cysts was 29.14 ± 24.53 ranged between 3 and 150 mm. All patients undergone CT scan and mean of values of density was 25.82 ± 11-82 Hounsfield. Surgical procedures were robotic approach in all case including total/extended thymectomy 35 (61.4%) and cyst resection/partial thymectomy 22 (38.6%). There were no mortality or recurrence. Major complications rate was 5.3%. No correlations were observed between preoperative features and complication. Pathological examination revealed microfoci of thymic tumor in four cases. Robot-assisted surgery for thymic cysts showed excellent early clinical outcomes with low rate of postoperative complications also in case of large lesion. Thymic cysts should not be underestimated due to the risk of coexistent thymic neoplasm.

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.

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.

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.

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.

Surgical management of compensatory sweating: A systematic review.

Endoscopic thoracic sympathectomy (ETS) surgery is a highly effective treatment of primary hyperhidrosis (PH) for the palms, face, axillae. Compensatory sweating (CS) is the most common and feared side effect of thoracic sympathectomy. CS is a phenomenon characterized by increased sweating in sites distal to the level of sympathectomy. Compensatory sweating is the main problem for which many patients give up surgery, losing the chance to solve their problem and accepting a poor quality of life. There are still no treatments that offer reliable solutions for compensatory sweating. The treatments proposed in the literature are scarce, with low case histories, and with uncertain results. Factors associated with CS are extension of manipulation of the sympathetic chain, level of sympathetic denervation, and body mass index. Therapeutic options include non surgical treatment and surgical treatment. Non surgical treatments include topical agents, botulinum toxin, systemic anticholinergics, iontophoresis. Surgical treatments include clip removal, extended sympathectomy and sympathetic chain reconstruction, although the efficacy is not well-established for all the methods. In this review we provide an overview of the treatments and outcomes described in the literature for the management of compensatory CS, with focus on surgical treatment.

Rate and Predictors of Unforeseen PN1/PN2-Disease in Surgically Treated cN0 NSCLC-Patients with Primary Tumor > 3 cm: Nationwide Results from Italian VATS-Group Database.

Background. Since no robust data are available on the real rate of unforeseen N1-N2 disease (uN) and the relative predictive factors in clinical-N0 NSCLC with peripheral tumours > 3 cm, the usefulness of performing a (mini)invasive mediastinal staging in this setting is debated. Herein, we investigated these issues in a nationwide database. Methods. From 01/2014 to 06/2020, 15,784 thoracoscopic major lung resections were prospectively recorded in the "Italian VATS-Group" database. Among them, 1982 clinical-N0 peripheral solid-type NSCLC > 3 cm were identified, and information was retrospectively reviewed. A mean comparison of more than two groups was made by ANOVA (Bonferroni correction for multiple comparisons), while associations between the categorical variables were estimated with a Chi-square test. The multivariate logistic regression model and Kaplan-Meyer method were used to identify the independent predictors of nodal upstaging and survival results, respectively. Results. At pathological staging, 229 patients had N1-involvement (11.6%), and 169 had uN2 disease (8.5%). Independent predictors of uN1 were SUVmax (OR: 1.98; CI 95: 1.44-2.73, p = 0.0001) and tumour-size (OR: 1.52; CI: 1.11-2.10, p = 0.01), while independent predictors of uN2 were age (OR: 0.98; CI 95: 0.96-0.99, p = 0.039), histology (OR: 0.48; CI 95: 0.30-0.78, p = 0.003), SUVmax (OR: 2.07; CI 95: 1.15-3.72, p = 0.015), and the number of resected lymph nodes (OR: 1.03; CI 95: 1.01-1.05, p = 0.002). Conclusions. The unforeseen N1-N2 disease in cN0/NSCLCs > 3 cm undergoing VATS resection is observable in between 12 and 8% of all cases. We have identified predictors that could guide physicians in selecting the best candidate for (mini)invasive mediastinal staging.

Uniportal-VATS vs. open McKeown esophagectomy: Surgical and long-term oncological outcomes.

Background: Till now there are very few reports about surgical results of Uniportal-VATS esophagectomy and no one about long-term outcomes. This study is the first comparing surgical and oncological outcomes of Uniportal-VATS with open McKeown esophagectomy, with the largest reported series and longest oncological follow-up. Methods: The prospectively collected clinical, surgical and oncological data of 75 patients, undergone McKeown esophagectomy at our Thoracic Surgery Department, from January 2012 to August 2022, were retrospectively analyzed. Nineteen patients underwent esophagectomy by thoracotomy and reconstruction according to McKeown technique while 56 by Uniportal-VATS approach. Gastric tubulization was performed totally laparoscopic or through a mini-laparatomic access and cervical anastomosis was made according to Orringer's technique. Results: The mean operative thoracic time was similar in both accesses (102.34 ± 15.21 min in Uniportal-VATS vs. 115.56 ± 23.12 min in open, p: 0.646), with a comparable number of mediastinal nodes retrieved (Uniportal-VATS:13.40 ± 8.12 vs. open:15.00 ± 6.86, p: 0.275). No case needed conversion from VATS to open. The learning curve in Uniportal-VATS was completed after 34 cases, while the Mastery was reached after 40. Both approaches were comparable in terms of minor post-operative complications (like pneumonia, lung atelectasis, anemization, atrial fibrillation, anastomotic-leak, left vocal cord palsy, chylothorax), while the number of re-operation for major complications (bleeding or mediastinitis) was higher in open group (21.0% vs. 3.6%, p: 0.04). Both techniques were also effective in terms of surgical radicality and local recurrence but VATS approach allowed a significantly lower chest tube length (11.89 ± 9.55 vs. 25.82 ± 24.37 days, p: 0.003) and post-operative stay (15.63 ± 11.69 vs. 25.53 ± 23.33, p: 0.018). The 30-day mortality for complications related to surgery was higher in open group (p: 0.002). The 2-, 5- and 8-year survival of the whole series was 72%, 50% and 33%, respectively. Combined 2- and 5-year OS in Uniportal-VATS group was 76% and 47% vs. 62% and 62% in open group, respectively (Log-rank, p: 0.286; Breslow-Wilcoxon: p: 0.036). No difference in DFS was recorded between the two approaches (5 year-DFS in Uniportal-VATS: 86% vs. 72%, p: 0.298). At multivariate analysis, only pathological stage independently affected OS (p: 0.02), not the surgical approach (p: 0.276). Conclusions: Uniportal-VATS seems to be a safe, feasible and effective technique for performing McKeown esophagectomy, with equivalent surgical and long-term oncological results to standard thoracotomy, but with a faster and unharmed recovery, and a quite short learning curve.

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.

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.

Surgical Resection of Pulmonary Metastases from Melanoma in Oligometastatic Patients: Results from a Multicentric Study in the Era of Immunoncology and Targeted Therapy.

In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies has revolutionized the treatment of patients with advanced stage III and stage IV melanoma. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM) in the era of ESTs. The aim of this study is to describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, in order to identify prognostic factors affecting survival and to provide a framework for more informed patient selection of treatmeant with lung surgery in the future. Clinical data of 183 patients who underwent metastasectomy of PmMM between June 2008 and June 2021 were collected among four Italian Thoracic Centers. The main clinical, surgical and oncological variables reviewed were: sex, comorbidities, previous oncological history, melanoma histotypes and primary site, date of primary cancer surgical treatment, melanoma growth phase, Breslow thickness, mutation pattern disease, stage at diagnosis, metastatic sites, DFI (Disease Free Interval), characteristics of lung metastases (number, side, dimension, type of resection), adjuvant therapy after lung metastasectomy, site of recurrence, disease-free survival (DFS) and cancer-specific survival (CSS; defined as the time interval between the first melanoma resection or lung metastasectomy and death from cancer). All patients underwent surgical resection of the primary melanoma before lung metastasectomy. Twenty-six (14.2%) patients already had a synchronous lung metastasis at the time of primary melanoma diagnosis. A wedge resection was performed in 95.6% of cases to radically remove the pulmonary localizations, while an anatomical resection was necessary in the remaining cases. The incidence of major post-operative complications was null, while only 21 patients (11.5%) developed minor complications (mainly air leakage followed by atrial fibrillation). The mean in-hospital stay was 4.46 ± 2.8 days. Thirty- and sixty-day mortality were null. After lung surgery, 89.6% of the population underwent adjuvant treatments (47.0% immunotherapy, 42.6% targeted therapy). During a mean FUP of 107.2 ± 82.3 months, 69 (37.7%) patients died from melanoma disease, 11 (6.0%) from other causes. Seventy-three patients (39.9%) developed a recurrence of disease. Twenty-four (13.1%) patients developed extrapulmonary metastases after pulmonary metastasectomy. The CSS from melanoma resection was: 85% at 5 years, 71% at 10 years, 54% at 15 years, 42% at 20 years and 2% at 25 years. The 5- and 10-year CSS from lung metastasectomy were 71% and 26%, respectively. Prognostic factors negatively affecting CSS from lung metastasectomy at multivariable analysis were: melanoma vertical growth (p = 0.018), previous metastatic sites other than lung (p < 0.001) and DFI < 24 months (p = 0.007). Our results support the evidence that surgical indication confirms its important role in stage IV melanoma with resectable pulmonary metastases, and selected patients can still benefit from pulmonary metastasectomy in terms of overall cancer specific survival. Furthermore, the novel systemic therapies may contribute to prolonged survival after systemic recurrence following pulmonary metastasectomy. Patients with long DFI, radial growth melanoma phase and no site of metastatization other than lung seem to be the best candidate cases for lung metastasectomy; however, to drive stronger conclusions, further studies evaluating the role of metastasectomy in patients with iPmMM are needed.