Giant cell interstitial pneumonia: case series with comprehensive ultrastructural analyses of "not only" hard metal pneumoconiosis.

AIMS: Giant cell interstitial pneumonia (GIP) is a fibrosing lung disease histologically characterized by centrilobular pulmonary fibrosis and cannibalistic intra-alveolar multinucleated giant cells. It is considered a form of pneumoconiosis caused particularly by secondary exposure to hard metals (cemented carbide or tungsten carbide). Hard metals are commonly used in various industrial applications, such as cutting tools, drilling tools, machine inserts, and other wear-resistant components. However, cases with unknown exposure that recurred in transplanted lungs have been described. This has led to the hypothesis of a complex etiopathogenesis, likely multifactorial, involving the coparticipation of immune mechanisms. We aimed to identify all the elements present in a series of GIP lung samples to better understand the pathogenic mechanisms of the disease. METHODS AND RESULTS: We describe five cases of histologically diagnosed GIP in patients with occupational exposure to metallic dust using ultrastructural characterization to identify metal dust and to quantify asbestos fibres. We found that tungsten was present in three cases, albeit in trace amounts in two of them. Numerous elements were identified in all samples, including asbestos fibres in patients with endstage pulmonary fibrosis. Furthermore, in one of the described cases the recurrence of the disease was also observed in transplanted lungs. CONCLUSION: These findings support the hypothesis that GIP may be due to elements other than hard metals, with asbestos possibly representing a contributory factor in the expression of a more severe fibrotic disease. The recurrence of GIP observed in transplanted organs strengthens the hypothesis of the existence of a not yet fully understood etiopathogenic immune mechanism.

Unlocking the Potential of Computed Tomography-Guided Tracers in Pinpointing Lung Lesions during Surgery: A Collaborative Multi-Institutional Journey.

Background: Multiple techniques exist for the preoperative localization of small, deeply located solid or subsolid pulmonary nodules to guide limited thoracoscopic resection. This study aims to conduct a multi-institutional comparison of three different tomography-guided tracers' methods. Methods: A retrospective multicenter cross-sectional study was conducted. All patients suitable for CT-guided tracers with microcoil (GROUP1, n = 58), hook wire (GROUP2, n = 86), or bioabsorbable hydrogel plug (GROUP3, n = 33) were scheduled for video-assisted thoracoscopic wedge resection. Outcome variables: successful nodule localization, safety, and the feasibility of the tracers' placement. A χ2 test or Fisher's test for expected numbers less than five and a Kruskal-Wallis test were used to analyze the categorical and continuous variables, respectively. For the power calculations, we used G*Power version 3.1.9.6. Results: One hundred seventy-seven patients underwent the localization and resection of 177 nodules detected with three different CT-guided tracers. A significant difference was recorded for cancer history (p = 0.030), respiratory function, Charlson comorbidity index (p = 0.018), lesion type (p < 0.0001), distance from pleura surface (p < 0.0001), and time between preoperative CT-guided tracers and surgical procedures (p < 0.0001). Four post-procedural complications were recorded and in GROUP2, four cases of tracer dislocations occurred. Finally, hook wire group was associated with the shortest surgical time (93 min, p = 0.001). Conclusions: All methods were feasible and efficient, resulting in a 100% success rate for the microcoils and the bioabsorbable hydrogel plugs and a 94.2% success rate for the hook wires. Our results highlight the need to choose a technique that is less stressful for the patient and helps the surgeon by extending the approach to deep nodules and resecting over the course of several days from deployment.

Tertiary lymphoid structures and B-cell infiltration are IPF features with functional consequences.

Background: Recent literature has shown the presence of B cells and autoantibodies in idiopathic pulmonary fibrosis (IPF) which would imply the presence of tertiary lymphoid structures (TLS, sites where the immune response is triggered), yet TLS are not considered features of the histological characteristics of IPF. Aim: This study aims to quantify the presence, size, and degree of activation of TLS in biopsied and explanted lungs from patients with early- and late-IPF, never treated with antifibrotics, and relate their presence and activity to the clinical course, disease progression, and lung inflammation. Methods: Immunohistochestry for B cells and CD4, CD8, and CD45 cells was performed in lung tissue from IPF patients: 18 at diagnosis (early), 39 explanted (end-stage), and 12 smoking controls. TLS activation was assessed by CD40 expression. Spirometry along 31 (12-72) months of follow-up was used to characterize end-stage IPF as slow progressors or rapid progressors. Results: B cells, along with other inflammatory cells, were higher in early- and end-stage IPF than in controls (p < 0.001). In rapid progressors, all inflammatory cells were higher than in slow progressors (p < 0.05). TLS were present in 100% of early- and end-stage IPF and in 50% of controls. In end-stage IPF, the TLS area and activation score were higher than in early IPF (p < 0.0001; p = 0.005) and controls (p < 0.04; p < 0.002). TLS activation score correlated with FVC decline during follow-up in rapid progressors (r = 0.73; p = 0.007) but not in slow progressors. Conclusions: A prominent B-cell infiltration, along with the presence of TLS, the activity of which correlates with FVC decline, is an important component of IPF from the beginning of the disease, likely playing an important role on its mechanism and progression.

Comparative Analysis of Comprehensive Genomic Profile in Thymomas and Recurrent Thymomas Reveals Potentially Actionable Mutations for Target Therapies.

Molecular profiles of thymomas and recurrent thymomas are far from being defined. Herein, we report an analysis of a comprehensive genetic profile (CGP) in a highly selected cohort of recurrent thymomas. Among a cohort of 426 thymomas, the tissue was available in 23 recurrent tumors for matching the biomolecular results obtained from primary and relapse samples. A control group composed of non-recurrent thymoma patients was selected through a propensity score match analysis. CGP was performed using the NGS Tru-SightOncology assay to evaluate TMB, MSI, and molecular alterations in 523 genes. CGP does not differ when comparing initial tumor with tumor relapse. A significantly higher frequency of cell cycle control genes alterations (100.0% vs. 57.1%, p = 0.022) is detected in patients with early recurrence (<32 months) compared to late recurrent cases. The CGPs were similar in recurrent thymomas and non-recurrent thymomas. Finally, based on NGS results, an off-label treatment or clinical trial could be potentially proposed in >50% of cases (oncogenic Tier-IIC variants). In conclusion, CGPs do not substantially differ between initial tumor vs. tumor recurrence and recurrent thymomas vs. non-recurrent thymomas. Cell cycle control gene alterations are associated with an early recurrence after thymectomy. Multiple target therapies are potentially available by performing a comprehensive CGP, suggesting that a precision medicine approach on these patients could be further explored.

Safety and Efficacy of Salvage Surgery after Treatment With Immune-Checkpoint Adjuvant Inhibitors for Advanced Non-Small Cell Lung Cancer: A Multicentric Study.

OBJECTIVE: In advanced non-small cell lung cancer (NSCLC), immune-checkpoint inhibitors (ICIs) can achieve significant clinical responses. This raises the question of whether to consider salvage surgery as a curative treatment option. Few case series reported encouraging results in terms of pathological response. However, intraoperative risk and postoperative morbidity have been highlighted. This study aims to assess the safety and feasibility of surgery after ICIs administration and to evaluate its effectiveness on the final pathological examination. METHODS: We retrospectively identified stages III-IVA NSCLC consecutive patients who underwent surgery with radical intent after ICIs at three National Centers (2016-2022). Before treatment, all patients were considered unresectable by a multidisciplinary discussion. After surgery, pathological response was evaluated according to the International Association for the Study of Lung Cancer (IASLC) recommendation. RESULTS: Thirty-one patients were included; pretreatment clinical stage was: IIIA in 4 patients (10%), IIIB in 13 (42%), IIIC in 3 (13%), and IVA in 11 (35%). Median treatment duration was four cycles. Only anatomical resections were performed, with lobectomy that represent the main type of resection (22 patients, 74%). A minimally invasive approach was performed in 10 patients (32%), with a conversion rate of 0%. Postoperative complications were observed in eight patients (25%). Complete pathologic response (CPR) and major pathologic response (MPR) were 48% and 16%, respectively. Two and 3-years survival were 88%. CONCLUSIONS: Based on our experience, salvage surgery of advanced NSCLC treated with ICIs confirm his feasibility and safety in responder patients. Moreover, it is associated with low morbidity, high CPR rate, and satisfying medium-term survival.

A new vessel filled and heart-beating human corpse model for VATS lobectomy training.

BACKGROUND: Nowadays, video-assisted thoracic surgery (VATS) lobectomy represents the treatment of choice for early-stage lung cancer. Over the years, different methods for VATS training have evolved. The aim of this study is to present an innovative beating-heart filled-vessel cadaveric model to simulate VATS lobectomies. METHODS: Via selective cannulation of the cadaver heart, the pulmonary vessels were filled with a gel to improve their haptic feedback. An endotracheal tube with a balloon on its tip then allowed movement of the heart chambers, transmitting a minimum of flow to the pulmonary vessels. A simulated OR was created, using all instrumentation normally available during surgery on living patients, with trainees constantly mentored by experienced surgeons. At the end of each simulation, the participants were asked 5 questions on a scale of 1 to 10 to evaluate the effectiveness of the training method ("1" being ineffective and "10" being highly effective). RESULTS: Eight models were set up, each with a median time of 108 min and a cost of €1500. Overall, 50 surgeons were involved, of which 39 (78%) were consultants and 11 (22%) were residents (PGY 3-5). The median scores for the 5 questions were 8.5 (Q1; IQR1-3 8-9), 8 (Q2; IQR1-3 7-9), 9 (Q3; IQR1-3 8-10), 9 (Q4; IQR1-3 8-10), and 9 (Q5; IQR1-3 8-10). Overall, the model was most appreciated by young trainees even though positive responses were also provided by senior surgeons. CONCLUSIONS: We introduce a new beating-heart filled-vessel cadaveric model to simulate VATS lobectomies. From this initial experience, the model is cost effective, smooth to develop, and realistic for VATS simulation.

Is There a Link between Chronic Obstructive Pulmonary Disease and Lung Adenocarcinoma? A Clinico-Pathological and Molecular Study.

Chronic Obstructive Pulmonary Disease (COPD) and lung cancer are strictly related. To date, it is unknown if COPD-associated cancers are different from the tumors of non-COPD patients. The main goal of the study was to compare the morphological/molecular profiles of lung adenocarcinoma (LUAD) samples of COPD, non-COPD/smokers and non-COPD/non-smokers, and to investigate if a genetic instability also characterized non-pathological areas. This study included 110 patients undergoing surgery for a LUAD, divided into three groups: COPD/smoker LUAD (38), non-COPD/smoker LUAD (54) and non-COPD/non-smoker LUAD (18). The tissue samples were systemically evaluated by pathologists and analyzed using a 30-gene Next Generation Sequencing (NGS) panel. In a subset of patients, tissues taken far from the neoplasia were also included. The non-COPD/smoker LUAD were characterized by a higher proliferative index (p = 0.001), while the non-COPD/non-smoker LUAD showed higher percentages of lepidic pattern (p = 0.008), lower necrosis, higher fibrosis, and a significantly lower mutation rate in the KRAS and PIK3CA genes. Interestingly, the same gene mutations were found in pathological and normal areas exclusively in the COPD/smokers and non-COPD/smokers. COPD/smoker LUAD seem to be similar to non-COPD/smoker LUAD, particularly for the genetic background. A less aggressive cancer phenotype was confirmed in non-COPD/non-smokers. The genetic alterations detected in normal lungs from smokers with and without COPD reinforce the importance of screening to detect early neoplastic lesions.

Real-world biomarker testing patterns: clinical-pathological portrait of early and late non-small cell lung cancer in hub and spoke North Italian centers.

Background: Lung cancer is still the main cause of cancer death. In the last decades, significant innovations were introduced in non-small cell lung cancer (NSCLC) treatment and management improving patient outcomes. The discovery of immune checkpoint inhibitors and the detection of an increasing list of actionable genetic alterations are enabling a tailored approach. Herein, we assessed in a pragmatic retrospective study the rate of biomarker tests within a large pulmonary pathology-based unit (PPU) network of the Veneto region (Northern Italy). Methods: Each PPU of 7 hubs and spoke centers implemented a biomarker database with pathologic and clinical data of patients with NSCLC diagnosis over 24 months. Results: Out of 1,817 NSCLC cases, 51% were advanced and 49% early stage, with 72% being adenocarcinomas. Programmed death ligand 1 expression and epidermal growth factor receptor mutations were available in most samples, 91% and 78%, respectively. Only 36% of advanced stages received all 5 biomarker tests with an increased rate over time. Co-occurring molecular alterations were detected in 42 cases (2%): the prevalence was (n=17) 41% and (n=25) 59% in early and late-stage adenocarcinomas, respectively. Conclusions: In this real-world study, while most patients received at least one biomarker test, less than 50% had all 5 biomarkers. The screening appeared to increase over time especially with the progressive use of next generation sequencing. Our results confirm the importance of systematic biomarker testing including all NSCLCs based on the evidence of several genomic alterations also in early-stage disease whose analysis may become relevant as neo-adjuvant targeted therapies are available. Keywords: Non-small cell lung cancer (NSCLC); biomarkers; actionable targets; lung cancer.

Cost-effectiveness of single-pill and separate-pill administration of antihypertensive triple combination therapy: a population-based microsimulation study.

BACKGROUND: Single-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective. METHODS: A cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty. RESULTS: Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61-1.14), with a mean cost differential of -€12 (95% CI -9,719-8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871-€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17-7,813) and €2,027 (95% CI 19-8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574-10,640 vs. €3,710, 95% CI 263-11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status. CONCLUSIONS: The SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.

Thoracic Ultrasound as an Alternative to Chest X-ray in Thoracic Surgery Patients: A Single-Center Experience.

Background/Objectives: Chest X-ray (CXR) is currently the most used investigation for clinical follow-up after major noncardiac thoracic surgery. This study explores the use of lung ultrasound (LUS) as an alternative to CXR in the postoperative management of patients who undergo major thoracic procedures. Methods: The patients in our cohort were monitored with both a CXR and a lung ultrasonography after surgery and the day after chest drain removal. The LUS was performed by a member of the medical staff of our unit who was blinded to both the images and the radiologist's report of the CXR. Findings were compared between the two methods. Results: In the immediate postoperative evaluation, 280 patients were compared, finding general agreement between the two procedures at 84% (kappa statistic, 0.603). The LUS showed a sensibility of 84.1%, a specificity of 84.3%, a positive predictive value (PPV) of 60.9%, and a negative predictive value (NPV) of 94.8%. We evaluated 219 out of 280 patients in the postdrainage-removal setting due to technical issues. Concordance between the methods in the postdrainage-removal setting was 89% (kappa statistic, 0.761) with the LUS demonstrating an 82.2% sensibility, a 93.2% specificity, a PPV of 85.7%, and an NPV of 91.3%. Conclusions: The results of this study showed a substantial agreement between LUS and CXR, suggesting that the LUS could reduce the number of X rays in certain conditions. The high NPV allows for the exclusion of PNX and pleural effusion without the need to expose patients to radiation. Discrepancies were noted in cases of mild pneumothorax or modest pleural effusion, without altering the clinical approach.

Tumor inflammatory microenvironment contribution to survival in resected upstaged adenocarcinomas.

INTRODUCTION: Tumor Inflammatory microenvironment (TIME) encompasses several immune pathways modulating cancer development and escape that are not entirely uncoded. The results achieved with immunotherapy elicited the scientific debate on TIME also in non-small cell lung cancer (NSCLC). We aimed to investigate whether TIME (in terms of PD-L1 expression and/or Tumor Infiltrating Lymphocytes - TILs) played a separate role in terms of survival (OS) in resected upstaged lung adenocarcinomas (ADCs), excluding other perioperative variables as confounders. MATERIALS AND METHODS: This retrospective study included 50 patients with a clinically resectable lung ADC, undergoing surgery (lobectomy or segmentectomy) at the Thoracic Unit of Padova University Hospital between 2016 and 2022 and receiving an unexpected pathological upstaging (IIB or higher). RESULTS: Despite microscopical variables increasing from IIB to IIIB, survival was not significantly related to them. OS was better in TIME-active patients (defined as the presence of positive PD-L1 and/or TILs>10 %) than double negatives (PD-L1-/TILs-) (p = 0.01). In IIB or higher ADCs, TIME-active patients showed an improved survival compared to double negatives, merging the current TIME theories. CONCLUSION: TIME seems to be associated with survival independently from other microscopical parameter, even in case of resected upstaged adenocarcinomas.

The COVID-19 Pandemic Was Associated with a Change in Therapeutic Management and Mortality in Heart Failure Patients.

Background: Heart failure (HF)-related mortality has been exacerbated by the COVID-19 pandemic; however, it is unclear how healthcare reassessment has contributed to the excess mortality versus SARS-CoV-2 infection itself. We aimed to assess how the pandemic affected the therapeutic management and prognosis of HF patients. Methods: We retrospectively reviewed the healthcare utilization databases of the Lombardy region (Italy) to identify all newly-diagnosed HF patients from January 2018 to December 2021. Outcomes were the utilization of HF therapies (Sacubitril/Valsartan; cardiac resynchronization therapy [CRT] and/or implantable cardioverter-defibrillator [ICD]; mechanical circulatory support [MCS]; heart transplantation [HTX]) and mortality. Cox regression models were fitted to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with the pandemic. Results: 36,130 and 17,263 patients were identified in the pre-pandemic and pandemic eras, respectively. The pandemic reduced Sacubitril/Valsartan utilization (HR = 0.77, 95% CI: 0.65-0.91) and CRT/ICD implantation (HR = 0.85, 95% CI: 0.78-0.92), but not MCS (HR = 1.11, 95% CI: 0.86-1.43) and HTX (HR = 0.88, 95% CI: 0.70-1.09). An increased mortality risk was observed during the pandemic (HR = 1.19, 95% CI: 1.15-1.23), which was attributable to SARS-CoV-2 infection (HR for non-COVID-19-related mortality = 1.01, 95% CI: 0.97-1.04). Conclusions: The COVID-19 pandemic was associated with a reduction in medical and interventional therapies for HF and an increase in mortality for HF patients.

Cost-effectiveness of outpatient adherence to recommendations for monitoring of patients hospitalized for heart failure.

AIMS: A set of indicators to assess the quality of care for patients hospitalized for heart failure was developed by an expert working group of the Italian Health Ministry. Because a better performance profile measured using these indicators does not necessarily translate to better outcomes, a study to validate these indicators through their relationship with measurable clinical outcomes and healthcare costs supported by the Italian National Health System was carried out. METHODS AND RESULTS: Residents of four Italian regions (Lombardy, Marche, Lazio, and Sicily) who were newly hospitalized for heart failure (irrespective of stage and New York Heart Association class) during 2014-2015 entered in the cohort and followed up until 2019. Adherence to evidence-based recommendations [i.e. renin-angiotensin-aldosterone system (RAS) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and echocardiograms (ECCs)] experienced during the first year after index discharge was assessed. Composite clinical outcomes (cardiovascular hospital admissions and all-cause mortality) and healthcare costs (hospitalizations, drugs, and outpatient services) were assessed during the follow-up. The restricted mean survival time at 5 years (denoted as the number of months free from clinical outcomes), the hazard of clinical outcomes (according to the Cox model), and average annual healthcare cost (expressed in euros per person-year) were compared between adherent and non-adherent patients. A non-parametric bootstrap method based on 1000 resamples was used to account for uncertainty in cost-effectiveness estimates. A total of 41 406 patients were included in this study (46.3% males, mean age 76.9 ± 9.4 years). Adherence to RAS inhibitors, beta-blockers, MRAs, and ECCs were 64%, 57%, 62%, and 20% among the cohort members, respectively. Compared with non-adherent patients, those who adhered to ECCs, RAS inhibitors, beta-blockers, and MRAs experienced (i) a delay in the composite outcome of 1.6, 1.9, 1.6, and 0.6 months and reduced risks of 9% (95% confidence interval, 2-14%), 11% (7-14%), 8% (5-11%), and 4% (-1-8%), respectively; and (ii) lower (€262, €92, and €571 per year for RAS inhibitors, beta-blockers, and MRAs, respectively) and higher costs (€511 per year for ECC). Adherence to RAS inhibitors, beta-blockers, and MRAs showed a delay in the composite outcome and a saving of costs in 98%, 84%, and 93% of the 1000 bootstrap replications, respectively. CONCLUSIONS: Strict monitoring of patients with heart failure through regular clinical examinations and drug therapies should be considered the cornerstone of national guidelines and audits.

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.

Robotic thymectomy in thymic tumours: a multicentre, nation-wide study.

OBJECTIVES: Robotic thymectomy has been suggested and considered technically feasible for thymic tumours. However, because of small-sample series and the lack of data on long-term results, controversies still exist on surgical and oncological results with this approach. We performed a large national multicentre study sought to evaluate the early and long-term outcomes after robot-assisted thoracoscopic thymectomy in thymic epithelial tumours. METHODS: All patients with thymic epithelial tumours operated through a robotic thoracoscopic approach between 2002 and 2022 from 15 Italian centres were enrolled. Demographic characteristics, clinical, intraoperative, postoperative, pathological and follow-up data were retrospectively collected and reviewed. RESULTS: There were 669 patients (307 men and 362 women), 312 (46.6%) of whom had associated myasthenia gravis. Complete thymectomy was performed in 657 (98%) cases and in 57 (8.5%) patients resection of other structures was necessary, with a R0 resection in all but 9 patients (98.6%). Twenty-three patients (3.4%) needed open conversion, but no perioperative mortality occurred. Fifty-one patients (7.7%) had postoperative complications. The median diameter of tumour resected was 4 cm (interquartile range 3-5.5 cm), and Masaoka stage was stage I in 39.8% of patients, stage II in 56.1%, stage III in 3.5% and stage IV in 0.6%. Thymoma was observed in 90.2% of patients while thymic carcinoma occurred in 2.8% of cases. At the end of the follow-up, only 2 patients died for tumour-related causes. Five- and ten-year recurrence rates were 7.4% and 8.3%, respectively. CONCLUSIONS: Through the largest collection of robotic thymectomy for thymic epithelial tumours we demonstrated that robot-enhanced thoracoscopic thymectomy is a technically sound and safe procedure with a low complication rate and optimal oncological outcomes.

Is chest tube capnography effective in differentiating between true and false air leaks after minimally invasive thoracic surgery?

OBJECTIVE: Air leak (AL) is the most frequent adverse event after thoracic surgery. When AL occurs, the concentration of the principal gas in the pleural space should be similar to that of air exhaled. Accordingly, we tried to develop a new method to identify AL by analyzing pCO2 levels in the air flow from the chest drainage using capnography. METHODS: This is a prospective observational study of 104 patients who underwent VATS surgery between January 2020 and July 2021. Digital drainage systems were used to detect AL. RESULTS: Eighty-two patients (79%) had lung resection. Among them, 19 had post-operative day 1 air leaks (median 67 ml/min). AL patients had higher intrapleural CO2 levels (median 24 mmHg) (p < 0.001). Median chest drainage duration was 2 days (range 1.0-3.0). Univariable logistic regression showed a linear and significant association between intrapleural CO2 levels and AL risk (OR 1.26, 95% CI 1.17-1.36, p < 0.001, C index: 0.94). The Univariable Gamma model demonstrated that an elevation in CO2 levels was linked to AL on POD1 (with an adjusted mean effect of 7.006, 95% CI 1.59-12.41, p = 0.011) and extended duration of drainage placement (p < 0.001). CONCLUSIONS: Intrapleural CO2 could be an effective tool to assess AL. The linear association between variables allows us to hypothesize the role of CO2 in the identification of AL. Further studies should be performed to identify a CO2 cutoff that will standardize the management of chest drainage.

Pathological complete response in a patient with pleural mesothelioma treated with immunotherapy: a case report.

The role of immunotherapy in the multimodal treatment for pleural mesothelioma (PM) is still under investigation, particularly in the preoperative setting. Pathological complete response (pCR) has been previously described after chemotherapy and immunotherapy; however, there is no prior experience reported with immunotherapy alone before surgery. We report the case of a 58-year-old male with biphasic PM treated with immunotherapy, resulting in a major clinical partial response. Following a multidisciplinary evaluation between thoracic surgeons, medical oncologists, pathologists, radiologists and radiation oncologists, the patient underwent surgery with radical intent through a right extended pleurectomy/decortication (eP/D). Histopathological examination of the specimen confirmed a pathological Complete Response (pCR). This case supports the feasibility and potential efficacy of combining preoperative immunotherapy with surgery in the management of advanced PM.