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OBJECTIVES Only few studies compared the surgical morbidity and mortality of thoracoscopic segmentectomy versus lobectomy for non-small-cell lung cancer, in particular, by relating the segmental resections with the corresponding anatomical lobes. METHODS We enrolled a total of 7487 patients who underwent VATS lobectomy (7269) or segmentectomy (218) from January 2014 to July 2019. A propensity score matching approach was used to account for potential confounding factors between the 2 groups. After matching, 349 lobectomies and 208 segmentectomies were included in the analysis. We analysed the operative and postoperative outcomes of video-assisted anatomical segmentectomy compared with video-assisted lobectomy and, in details, the results of segmentectomy with its corresponding lobectomy in a large cohort of patients from the Italian VATS Group Registry. RESULTS The overall conversion rate to thoracotomy was not statistically different between the groups (27 patients 8% vs 7 patients 3%, P = 0.1). The lobectomy group had a greater number of resected lymph nodes (median 11 vs 8, P = 0.006). No significant differences were detected in 30-day mortality (1.4%, 5 patients vs 0.9%, 2 patients), overall complications (18%, 62 patients vs 14%, 29 patients) and prolonged air leakage (31 patients, 9% vs 12 patients, 6%) between lobectomy and segmentectomy, respectively. No statistical differences were found regarding the median duration of drainage (3.2 days, P = 1) and the overall median length of hospital stay (6.4 days, P = 0.1) between the 2 groups. In the context of segmentectomy versus corresponding lobectomy, the right upper lobectomy compared with right upper segmentectomy showed a higher number of resected lymph nodes (P = 0.027). No statistical differences were reported in terms of conversion rate and postoperative complication and mortality. CONCLUSIONS Segmentectomy could be considered a safe procedure without significant differences compared to thoracoscopic lobectomy in terms of postoperative morbidity and mortality.

OBJECTIVES This study compares the uniportal with the 3-portal video-assisted thoracic surgery (VATS) by examining the data collected in the Italian VATS Group Database. The primary end point was early postoperative pain; secondary end points were intraoperative and postoperative complications, surgical time, number of dissected lymph nodes and length of stay. METHODS This was an observational, retrospective, cohort, multicentre study on data collected by 49 Italian thoracic units. Inclusion criteria were clinical stage I–II non-small-cell lung cancer, uniportal or 3-portal VATS lobectomy and R0 resection. Exclusion criteria were cT3 disease, previous thoracic malignancy, induction therapy, significant comorbidities and conversion to other techniques. The pain parameter was dichotomized: the numeric rating scale ≤3 described mild pain, whereas the numeric rating scale score >3 described moderate/severe pain. The propensity score-adjusted generalized estimating equation was used to compare the uniportal with 3-portal lobectomy. RESULTS Among 4338 patients enrolled from January 2014 to July 2017, 1980 met the inclusion criteria; 1808 patients underwent 3-portal lobectomy and 172 uniportal surgery. The adjusted generalized estimating equation regression model using the propensity score showed that over time pain decreased in both groups (P CONCLUSIONS Data from the Italian VATS Group Database showed that in clinical practice uniportal lobectomy seems to entail a higher risk of moderate/severe pain on second and third postoperative days.

OBJECTIVESInherent technical aspects of pulmonary lobectomy by video-assisted thoracoscopic surgery (VATS) may limit surgeons’ ability to deal with factors predisposing to complications. We analysed complication rates after VATS lobectomy in a prospectively maintained nationwide registry.METHODSThe registry was queried for all consecutive VATS lobectomy procedures from 49 Italian Thoracic Units. Baseline condition, tumour features, surgical techniques, devices, postoperative care, complications, conversions and the reasons thereof were detailed. Univariable and multivariable regressions were used to assess factors potentially linked to complications.RESULTSFour thousand one hundred and ninety-one VATS lobectomies in 4156 patients (2480 men, 1676 women) were analysed. The median age-adjusted Charlson index of the patients was 4 (interquartile range 3–6). Grade 1 and 2 and Grade 3–5 complications were observed in 20.1% and in 5.8%, respectively. Ninety-day mortality was 0.55%. The overall conversion rate was 9.2% and significantly higher in low-volume centres (CONCLUSIONSVATS lobectomy is a safe procedure even in medically compromised patients. An improved classification system for conversions is proposed and prevention strategies are suggested to reduce conversion rates and possibly complications in less-experienced centres.

Accurate staging of early non-small cell lung cancer is fundamental for selecting the best treatment. The aim of this study was to identify risk factors for nodal upstaging after video-assisted thoracoscopic lobectomy for clinical T1-3N0 tumors.From 2014 to 2017, 3276 thoracoscopic lobectomies were recorded in the prospective database "Italian VATS Group". Linear and multiple logistic regression models were adapted to identify independent predictors of nodal upstaging and factors associated with progression in postoperative N status.Nodal upstaging was found in 417 cases (12.7%), including 206 cases (6.2%) of N1-positive nodes, 81 cases of N2 nodes (2.4%), and 130 cases (4%) of involvement of both N1 + N2 nodes. A total of 241 (7.3%) patients had single-station nodal involvement, whereas 176 (5.3%) had multiple-station involvement. In the final regression model, the tumor grade, histology, pathologic T status, and 12 resected nodes were independent predictors of nodal upstaging.The number of resected lymph nodes seems to predict nodal upstaging better than the type of intraoperative lymph node management. Other preoperative risk factors correspond to those for which the current guidelines of the European Society of Thoracic Surgery recommend more extensive preoperative mediastinal staging.

Background: The expertise curve of video-assisted thoracoscopic surgery (VATS) lobectomies still stirs debate and controversy both because of the number of procedures to carry out and of the evaluation of the learning threshold. The purpose of our study was the examination of the variables related to the learning curve of the video-assisted approach, to establish what may be an expression of the technical maturity of the surgeon. Methods: The National Register for VATS lobectomy built in 2013 was used to collect data from 65 Thoracic Surgery Units. Out of more than 3,700 patients enrolled, only information from Units with ≥100 VATS lobectomies were retrospectively analysed. Unpaired Student’s t-tests, Fisher’s exact tests, Pearson’s χ 2 were applied as needed. Cumulative summative analysis and one-way ANOVA were used to identify the expertise curve of VATS lobectomy. Results: Ten institutions contributed a total of 1,679 patients, who were divided into three uniform groups according to the chronological sequence of surgery. The length of utility incision, the number of dissected lymph nodes and the operative time were not statistically significant (P=0.999, P=0.972 and P=0.307, respectively) among groups. Conversion to thoracotomy and postoperative air leaks occurred in 125 (7.44%) and 109 (6.49%) patients, gradually declined in Group 3 with statistical signi cance (P=0.048 and P=0.00086). Conclusions: The conversion rate and the percentage of air leaks seem to de ne the expertise of VATS lobectomy, being linked to the ability to manage more complicated surgical cases or intraoperative adverse events.

OBJECTIVES: Inherent technical aspects of pulmonary lobectomy by video-assisted thoracoscopic surgery (VATS) may limit surgeons’ ability to deal with factors predisposing to complications. We analysed complication rates after VATS lobectomy in a prospectively maintained nationwide registry. METHODS: The registry was queried for all consecutive VATS lobectomy procedures from 49 Italian Thoracic Units. Baseline condition, tumour features, surgical techniques, devices, postoperative care, complications, conversions and the reasons thereof were detailed. Univariable and multivariable regressions were used to assess factors potentially linked to complications. RESULTS: Four thousand one hundred and ninety-one VATS lobectomies in 4156 patients (2480 men, 1676 women) were analysed. The median age-adjusted Charlson index of the patients was 4 (interquartile range 3–6). Grade 1 and 2 and Grade 3–5 complications were observed in 20.1% and in 5.8%, respectively. Ninety-day mortality was 0.55%. The overall conversion rate was 9.2% and significantly higher in low-volume centres (

In non small cell lung cancer (NSCLC) patients undergoing surgery after induction chemotherapy, all mediastinal lymphnodes potentially involved by tumor should be resected whenever possible. Paratracheal bilateral lymphadenectomy for left sided tumors can be disabling, i.e. median sternotomy plus a thoracotomy to reach the subcarinal region. From the right side, an extensive ipsilateral dissection is feasible through a standard thoracotomy, but contralateral lymphnodes, especially in the left hilum and aortopulmonary window are considered inaccessible. A technical tip is shown to reach and dissect the left paratracheal and aortopulmonary window nodes through a simple right thoracotomy in right-lung cancer. The procedure has been carried out in 3 cases and proved to be technically feasible. The value of such a procedure as to staging accuracy, local disease control and survival should be evaluated in a clinical trial setting.

Objective: The objective of the study is to analyse the causes and impact of conversion from VATS to thoracotomy identifying any possible pre-operative risk factors and related consequences. Methods: Data from patient who underwent VATS lobectomy (VATS-L) for NSCLC at VATS Group participating centres were retrospectively analysed and divided in two groups: patients treated with VATS-L and patients who suffered from conversion. Predictors of conversion were assessed with univariate and multivariable exact logistic regression. Complications were evaluated as dependent variables of conversion in a Cox multivariable logistic regression model. Results: A total of 4629 patients underwent planned VATS-L for NSCLC and of these, 432 (9.3%) required conversion; the most frequent causes were bleeding (30.4%) and fibro-calcified hilar lymph nodes (23.9%). The independent risk factors at multivariable analysis model were sex male (OR 1.458, p < 0.01), age older than 70years (OR 1.248, p = 0.036) and the clinically node-positive disease (OR 2.258, p < 0.01). The mortality rate was similar, but the percentage of patients who suffered from any complication (41.7% vs 24.4%, p < 0.01), the complication rate (65% vs 32.2%, p < 0.01), chest tube duration (p < 0.01) and the hospitalisation rate (p < 0.01) were higher for patients converted. Atrial fibrillation (OR 1.471, p = 0.019), prolonged air leak (OR 1.403, p = 0.043), blood transfusions (OR 4.820, p < 0.01), sputum retention (OR 1.80, p = 0.027) and acute kidney failure (OR 2.758, p = 0.03) were significantly associated with conversion at multivariable analysis. Conclusions: Conversion is associated with increased surgical morbidity, blood loss and hospital stay. Sex male, old age and the clinical involvement of lymph nodes were the strongest predictors of conversion.

The COVID-19 pandemic has changed routine care practice for older persons, especially in those with frailty living in long term care (LTC) facilities. Due to the high mortality rates of Nursing home (NH) residents during the first wave of the COVID-19 pandemic, priority for COVID-19 vaccinations was given to this vulnerable population. However, the safety and efficacy of such vaccines in older frail elders remains questionable due to the fact that initial randomized clinical trials (RCTs) for such vaccines did not include this population. This type of discrimination in patient participation in RCTs continues and has been recognized in the literature. Nevertheless, in the context of a worldwide emergency, COVID-19 vaccination in older persons living in LTC facilities may provide a solid basis to protect against negative outcomes, such as COVID-19 infection and death. In this report, we present the protocol of the GeroCovid Vax study, an Italian study that began in February 2021 which is aimed at investigating the safety and efficacy of the anti-SARS-CoV-2 vaccinations in older persons living in LTCs. This protocol specially aims to continuously and closely monitor events related to- and following- the anti-SARS-CoV-2 vaccination in elderly living in LTC facilities. In this report, we will provide information related to the study protocol and describe baseline characteristics of the sample.

Italy was one of the first western countries to embrace the first wave of COVID-19 and undergo detrimental outcomes in older adults in different clinical settings, especially in those with comorbidity and frailty. In addition, older nursing home (NH) residents had significantly higher mortality rates most likely due to the increased susceptibility of infection due to combined physical vulnerability and risks linked to the NH living environment itself. Different reports throughout Italy have rapidly highlighted selected outcomes related to COVID-19 in older patients being treated in acute and long-term care (LTC) settings. However, the majority of these studies are single center studies. Thus, it remains fundamental to collect large data from prospective based-population studies in order to identify preventive and therapeutic COVID-19 risk/protective factors correlated with COVID-19 health status outcomes. In this commentary paper, we will discuss different Italian reports according to clinical settings and highlight the importance of GeroCovid Observational and GeroCovid Vax, two large population based prospective studies in Italy.

We compare the perioperative course, postoperative pain, and quality-of-life (QOL) in patients undergoing anatomic resections of early-stage lung cancer by means of robotic surgery (RATS), video-assisted thoracic surgery (VATS), or muscle-sparing thoracotomy (OPEN), 169 consecutive patients with known/suspected lung cancer, candidates to anatomic resection, were enrolled in a single-center prospective study from April 2016 to December 2018. EORTC QLQ-C30 and QLQ-LC13 scores were obtained preoperatively and, at three time points, postoperatively. RATS and VATS groups were matched for ASA scores, while RATS and open surgery were matched for gender, ASA score, cancer stage, and tumor size, 58 patients underwent open surgery, 58 had VATS, and 53 had RATS. Hospital stay was shorter after RATS than OPEN (median 4.5 versus 5, p = 0.047). Comparing matched RATS and VATS groups, the number of hilar lymph nodes and nodal stations removed was significantly higher in the former approach (p = 0.01 vs. p &lt, 0.0001), conversely, pain at 2 weeks was slightly lower after VATS (p = 0.004). No significant difference was observed in conversions, complications, duration of surgery, and postoperative hospitalization. The robotic approach was superior to OPEN in terms of QOL, pain, and length of postoperative stay and showed improved lymph node dissection compared to VATS.

IntroductionWe report the results of the first prospective international randomized control trial to compare the perioperative outcome and surgical radicality of the robotic approach with those of traditional video-assisted surgery in the treatment of early-stage lung cancer.MethodsPatients with clinical stage T1–T2, N0–N1 non-small cell lung cancer (NSCLC) were randomly assigned to robotic-assisted thoracoscopic surgery (RATS) or video-assisted thoracic surgery (VATS) resection arms. The primary objective was the incidence of adverse events including complications and conversion to thoracotomy. The secondary objectives included extent of lymph node (LN) dissection and other indicators.ResultsThis trial was closed at 83 cases as the probability of concluding in favor of the robot arm for the primary outcome was null according to the observed trend. In this study, we report the results of the analysis conducted on the patients enrolled until trial suspension. Thirty-nine cases were randomized in the VATS arm and 38 in the robotic arm. Six patients were excluded from analysis. Despite finding no difference between the two arms in perioperative complications, conversions, duration of surgery, or duration of postoperative stay, a significantly greater degree of LN assessment by the robotic technique was observed in regards to the median number of sampled LN stations [6, interquartile range (IQR) 4–6 vs. 4, IQR 3–5; p = 0.0002], hilar LNs (7, IQR 5–10 vs. 4, IQR 2–7; p = 0.0003), and mediastinal LNs (7, IQR 5–10 vs. 5, IQR 3–7; p = 0.0001).ConclusionsThe results of this trial demonstrated that RATS was not superior to VATS considering the perioperative outcome for early-stage NSCLC, but the robotic approach allowed an improvement of LN dissection. Further studies are suggested to validate the results of this trial.Clinical Trial Registrationclinicaltrials.gov, identifier NCT02804893.

Simple Summary Serum metabolite profiles were compared in healthy participants and lung cancer individuals in two independent screening studies. A reduced level of lipids, particularly cholesteryl esters, was observed in cancer patients. Despite several compounds showing significant differences between cancer patients and healthy controls within each study, only a few cancer-related features were common when both studies were compared, including reduced levels of LPC(18:0). A large heterogeneity of serum metabolomes was observed, both within and between studies, which impaired the accuracy of classifiers based on specific metabolites. Abstract Serum metabolome is a promising source of molecular biomarkers that could support early detection of lung cancer in screening programs based on low-dose computed tomography. Several panels of metabolites that differentiate lung cancer patients and healthy individuals were reported, yet none of them were validated in the population at high-risk of developing cancer. Here we analyzed serum metabolome profiles in participants of two lung cancer screening studies: MOLTEST-BIS (Poland, n = 369) and SMAC-1 (Italy, n = 93). Three groups of screening participants were included: lung cancer patients, individuals with benign pulmonary nodules, and those without any lung alterations. Concentrations of about 400 metabolites (lipids, amino acids, and biogenic amines) were measured by a mass spectrometry-based approach. We observed a reduced level of lipids, in particular cholesteryl esters, in sera of cancer patients from both studies. Despite several specific compounds showing significant differences between cancer patients and healthy controls within each study, only a few cancer-related features were common when both cohorts were compared, which included a reduced concentration of lysophosphatidylcholine LPC (18:0). Moreover, serum metabolome profiles in both noncancer groups were similar, and differences between cancer patients and both groups of healthy participants were comparable. Large heterogeneity in levels of specific metabolites was observed, both within and between cohorts, which markedly impaired the accuracy of classification models: The overall AUC values of three-state classifiers were 0.60 and 0.51 for the test (MOLTEST) and validation (SMAC) cohorts, respectively. Therefore, a hypothetical metabolite-based biomarker for early detection of lung cancer would require adjustment to lifestyle-related confounding factors that putatively affect the composition of serum metabolome.

Background Robotic surgery is increasingly used to resect lung cancer. However costs are high. We compared costs and outcomes for robotic surgery, video-assisted thoracic surgery (VATS), and open surgery, to treat non-small cell lung cancer (NSCLC). Methods We retrospectively assessed 103 consecutive patients given lobectomy or segmentectomy for clinical stage I or II NSCLC. Three surgeons could choose VATS or open, the fourth could choose between all three techniques. Between-group differences were assessed by Fisher's exact, two-way analysis of variance (ANOVA), and Wilcoxon-Mann-Whitney test. P values

Objectives Vascular injuries are among the most severe causes of unplanned conversion during VATS lobectomies. The study aimed to analyse the incidence of vascular injuries and their risk factors during VATS lobectomy. Methods The Italian VATS lobectomy Registry was used to collect data from 66 Thoracic Surgery Units. From 2013 to October 2016 (out of more than 3,700 patients enrolled) only information from Units with an enrollment >100 VATS lobectomies were retrospectively analysed. Logistic regression analysis was performed on selected variables of the univariate analysis. Results Ten institutions contributed a total of 1,679 patients. Vascular injuries leading to conversion occurred in 44 (2.6%) patients. Years of experiences were inversely related to the risk of vascular injuries. Univariate analysis showed age, gender, surgical activity, Charlson Index Score and number of resected lymph nodes like significantly associated variables. Multivariate analysis revealed that number of resected lymph nodes, VATS experience ratio (number of VATS lobectomies/total lobectomies performed in the same year at same centre), and surgical activity of the centre were significantly associated with the risk of conversion. Unplanned thoracotomy was correlated with postoperative morbidity. Conclusion Vascular injuries in VATS lobectomies represented a rare complication which could directly affect the postoperative outcomes. The predictive factors for conversion were multifactorial and depended on characteristics of centres and surgeons’ seniority. Minimally invasive VATS lobectomy approaches did not influence the risk of vascular damages.

Objectives In-vivo characterization of malignant pleural mesothelioma (MPM) with 11C-methionine PET/computed tomography (MET PET). Methods Between September 2014 and February 2016, 30 consecutive patients with clinical suspicion of MPM were prospectively recruited. The study was approved and registered at www.clinicaltrials.gov (NCT02519049). Patients were evaluated at baseline with MET PET (experimental) and fluorine-18 fluorodeoxyglucose PET/computed tomography (FDG PET) (standard). Principal parameters analyzed were SUVmax, SUVmean, metabolic tumor volume (MTV), and metabolic tumor burden (MTB = MTV ×SUVmean). The reference standard for diagnostic performance was based on histology. Results The presence of malignancy was confirmed in 29/30 patients: 23 (76.6%) with MPM (20 epithelioid, two biphasic, and one sarcomatoid), five (16.6%) with adenocarcinoma of the lung, and one (3.3%) with an undifferentiated carcinoma. In one case, diagnosis was benign pleural inflammation. All tumors showed increased uptake of 11C-methionine: median SUVmax, SUVmean, MTV, and MTB were, respectively, 5.70 [95% confidence interval (CI): 4.51-6.79], 3.15 (95% CI: 2.71-3.40), 33.85 (95% CI: 14.08-66.64), and 105.25 (95% CI: 41.77-215.25). Pathology data revealed MTV and MTB to be significantly higher in nonepithelioid histology (P < 0.05). The other parameters showed a homogeneous distribution across the tumor types. Overall, MET PET identified 49 lymph nodes, compared with 34 nodes on FDG PET, demonstrating a sensitivity of 91% (95% CI: 80-96%), a positive predictive value of 92% (95% CI: 82- 97%), and an accuracy of 85% (P = 0.0042). Conclusions MET PET is able to characterize MPM lesions regardless of histology. This technique shows higher sensitivity than FDG PET for the identification of secondary lymph nodes.

Small-cell lung cancer (SCLC) comprises 13-20% of all lung cancers but is the fifth leading cause of cancer death worldwide. SCLC prognosis remains poor despite improvements in diagnosis and therapy over the last 30 years. Current treatment is systemic chemotherapy, flanked by thoracic irradiation for limited stage disease; however, about two-thirds of patients are diagnosed with extensive stage disease when thoracic irradiation is not worthwhile. Randomized trials on surgical resection in patients with limited stage disease conducted in the pre-PET era, when both staging and treatment were inadequate, did not support a role for surgery in disease management. However recent retrospective and population-based studies indicate that outcomes after surgery in patients with very early SCLC are comparable to those in patients with non-SCLC, and that survival is better than in SCLC patients not given surgery. CT screening identifies SCLC at an earlier stage - with better survival - than usual care, and offers the hope that more SCLC patients may become long-term survivors. However, cases must be exhaustively staged to identify those likely to benefit from surgery. Finding a specific SCLC marker to facilitate early diagnosis remains a priority.

Background: Complete thymectomy is recommended for thymic malignancies to reduce local recurrence and the likelihood of the long-term development of myasthenia gravis (MG). Thymus-conserving surgery (thymomectomy) seems to yield similar results, but evidence is still limited. The objective of this study was to assess if the oncological outcome, in terms of overall survival (OS) and disease-free survival (DFS), are comparable between radical thymectomy vs. conservative thymomectomy patients, and to assess if the outcome of the video-assisted thoracoscopic surgery (VATS) approach was similar to open surgery approach. Methods: We retrospectively analyzed 157 consecutive patients with either resectable thymoma or thymic carcinoma from two Italian centers (Humanitas Research Hospital, Milan, and Humanitas Gavazzeni, Bergamo) between 1997 and 2013 who underwent thymomectomy or extended thymectomy with the VATS or open approach; the patients with Miastenia Gravis underwent radical thymectomy. The patients were followed through physical examinations and phone interviews. Results: Thymomectomy and thymectomy were performed on 86 (54.8%) and 71 (45.2%) patients, respectively. Prognostic factors and comorbidities were comparable in the two groups. The median follow-up was 77 months. Cox proportional hazards model revealed that Masaoka advanced stage and thymic carcinoma of WHO classification were independent predictive factors for overall survival, but that the extent of surgery and the approach used (minimally invasive versus open) were not. Notably, five- and ten-year survival rates were similar in the two groups. Conclusions: In our experience, radical thymectomy and conservative thymomectomy did not differ in terms of disease-free and overall survival rates. In nonmyasthenic patients with early-stage resectable thymic malignancy, minimally invasive thymomectomy provided equivalent results to open thymectomy. Our results should be interpreted with caution due to the retrospective nature of the study. Well-designed, adequately-powered studies should be very welcome to increase the quantity and the quality of clinical evidence before incorporating this procedure in future guidelines.