Impact of High-Grade Patterns in Early-Stage Lung Adenocarcinoma: A Multicentric Analysis.

OBJECTIVE: The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a significantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. METHODS: We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Differences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-high-grade and high-grade patterns. RESULTS: Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a significant better prognosis compared to T1a-b-c with high-grade pattern (p = 0.020), but the latter had similar OS compared to T2a (p = 0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a significantly better DFS compared to those with high-grade patterns (p = 0.034), and it was similar to T2a (p = 0.839). Multivariable analysis confirms the role of T descriptor according to high-grade pattern both for OS (p = 0.024; HR 1.285 95% CI 1.033-1.599) and DFS (p = 0.003; HR 1.196, 95% CI 1.054-1.344, respectively). These results were confirmed after the propensity score matching analysis. CONCLUSIONS: pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors.

Prognostic factors for survival in advanced thymomas: The role of the number of involved structures.

BACKGROUND AND OBJECTIVES: The Masoka-Koga and tumor node metastases staging systems for thymoma are based on structures involved, but the prognostic role of the number of infiltrated/involved structures is still debated. We analyzed the prognostic role of involved structures and their combinations in locally advanced thymomas patients. METHODS: Data on 174 surgically treated locally advanced thymoma patients from 1/01/1990 to 31/12/2015 were reviewed. Clinical and pathological characteristic, involved structures, number of involved structures and different combinations were correlated to cancer specific survival (CSS) using Kaplan-Meier product-limit method. RESULTS: Five and 10-year CSS was 92% and 87%. Masaoka Stage 3 (p < 0.001), absence of pericardial involvement (p = 0.001), number of involved structures (p = 0.018), R0 (p < 0.001) and adjuvant radiotherapy (p = 0.008) were favorable prognostic CSS factors. A significant better prognosis was present in ≤2 involved structures vs >2 involved structures (5- and 10-year CSS: 95% and 93% vs. 80% and 51%). Multivariable analysis confirmed as independent prognostic factor R0 (p = 0.033, hazard ratio [HR]: 0.093, 95% confidence interval [CI] 0.010-0.827) and number of involved structures (p = 0.046, HR: 0.187, 95% CI: 0.036-0.968). In Masaoka Stage 3, patients with ≤2 involved structures had a significant better CSS than patients with >2 (10-year CSS: 98% vs. 73%, p = 0.008). CONCLUSIONS: The number of involved structures and the concomitant involvement of the pericardium seems to be associated with a poor prognosis in surgically treated advanced thymoma patients.

Prognostic impact of lung adenocarcinoma second predominant pattern from a large European database.

BACKGROUND AND OBJECTIVES: Adenocarcinoma patterns could be grouped based on clinical behaviors: low- (lepidic), intermediate- (papillary or acinar), and high-grade (micropapillary and solid). We analyzed the impact of the second predominant pattern (SPP) on disease-free survival (DFS). METHODS: We retrospectively collected data of surgically resected stage I and II adenocarcinoma. SELECTION CRITERIA: anatomical resection with lymphadenectomy and pathological N0. Pure adenocarcinomas and mucinous subtypes were excluded. Recurrence rate and factors affecting DFS were analyzed according to the SPP focusing on intermediate-grade predominant pattern adenocarcinomas. RESULTS: Among 270 patients, 55% were male. The mean age was 68.3 years. SPP pattern appeared as follows: lepidic 43.0%, papillary 23.0%, solid 14.4%, acinar 11.9%, and micropapillary 7.8%. The recurrence rate was 21.5% and 5-year DFS was 71.1%. No difference in DFS was found according to SPP (p = .522). In patients with high-grade SPP, the percentage of SPP, age, and tumor size significantly influenced DFS (p = .016). In patients with lepidic SPP, size, male gender, and lymph-node sampling (p = .005; p = .014; p = .038, respectively) significantly influenced DFS. CONCLUSIONS: The impact of SPP on DFS is not homogeneous in a subset of patients with the intermediate-grade predominant patterns. The influence of high-grade SPP on DFS is related to its proportion in the tumor.

Arylacetamide Deacetylase Enzyme: Presence and Interindividual Variability in Human Lungs.

Human arylacetamide deacetylase (AADAC) is a single microsomal serine esterase involved in the hydrolysis of many acetyl-containing drugs. To date, the presence and activity of the AADAC enzyme in human lungs has been scarcely examined. We investigated its gene and protein expression as well as interindividual variations in AADAC activities in a large number of human lungs (n = 25) using phenacetin as a selective substrate. The kinetic parameters K m and V max were determined. Our findings highlighted a high interindividual variability in both AADAC mRNA levels and hydrolysis activities. Furthermore, for the first time we demonstrated the presence of the AADAC protein in various lung samples by means of immunoblot analysis. As a comparison, phenacetin hydrolysis was detected in pooled human liver microsomes. Lung activities were much lower than those found in the liver. However, similar K m values were found, which suggests that this hydrolysis could be due to the same enzyme. Pulmonary phenacetin hydrolysis proved to be positively correlated with AADAC mRNA (*P < 0.05) and protein (*P < 0.05) levels. Moreover, the average values of AADAC activity in smokers was significantly higher than in nonsmoker subjects (*P < 0.05), and this might have an important role in the administration of some drugs. These findings add more information to our knowledge of pulmonary enzymes and could be particularly useful in the design and preclinical development of inhaled drugs. SIGNIFICANCE STATEMENT: This study investigated the presence and activity of the AADAC enzyme in several human lungs. Our results highlight high interindividual variability in both AADAC gene and protein expression as well as in phenacetin hydrolysis activity. These findings add more information to our knowledge of pulmonary enzymes and could be particularly useful in the design and preclinical development of inhaled drugs.

Nodal upstaging evaluation in NSCLC patients treated by robotic lobectomy.

BACKGROUND: Open pulmonary resection is considered the gold standard treatment of early-stage non-small cell lung cancer (NSCLC). However, in the last decades, the use of minimal-invasive techniques has given promising results. Survival in lung cancer, after surgery, depends on the number of pathological nodes (pN), thus lymph nodal upstaging can be considered a surrogate for surgical quality of the procedure. Several studies have demonstrated a lower rate of upstaging in video-assisted thoracic surgery than in open surgery, suggesting an approach-related difference in lymphadenectomy. Features of robotic technique could consent a lymph nodal dissection similar to open surgery. The aim of the study is to compare nodal upstaging between thoracotomy and robotic approaches to evaluate the oncologic radicality. METHODS: Between January 2013 and December 2016, 212 consecutive cN0 NSCLC patients underwent lobectomy and lymphadenectomy (N1 + N2 stations) by either thoracotomy (Open Group) or robotic surgery (Robotic Group). RESULTS: Lobectomy and lymphadenectomy were performed in 106 cN0-cN1 NSCLC patients by robotic surgery and in 106 cN0-cN1 NSCLC patients by open surgery. A mean of 14.42 ± 6.99 lymph nodes was removed in the Robotic Group (RG) and a mean of 14.32 ± 7.34 nodes in the Open Group (OG). Nodal upstaging was observed in 22 (20.75%) RG patients and in 19 OG (17.92%) patients. CONCLUSIONS: Robotic lobectomy for clinical N0-N1 NSCLC appears to be equivalent to thoracotomy in terms of efficacy of lymph node dissection and nodal upstaging. Given that the nodal upstaging is a surrogate of quality of surgery, we can consider robotic lobectomy an appropriate procedure which ensures similar result to the open approach.

Is left upper lobectomy always worthwhile for early stage lung cancer? A comparison between left upper lobectomy, trisegmentectomy, and lingulectomy.

BACKGROUND AND OBJECTIVES: Lobectomy is the gold standard treatment for resectable Non-Small Cell Lung Cancer (NSCLC). We compared oncological outcomes of patients undergoing a "multi-segmentectomy" (trisegmentectomy or lingulectomy) and left upper lobectomy for early stage (T1-2, N0) NSCLC of the left upper lobe. METHODS: We retrospectively analyzed all patients with pathological early stage (T1-T2 N0) NSCLC located in left upper lobe who underwent a lobectomy, a trisegmentectomy, or a lingulectomy between 2006 and 2013, focusing on surgical and oncological outcomes. RESULTS: Among 159 patients, 105 patients underwent a lobectomy and 54 patients a multi-segmentectomy (33 lingulectomy and 21 trisegmentectomy). Actuarial mean Overall Survival was 87 months (95%CI 79-95) and 89 months (95%CI 76-101) for lobectomies and multi-segmentectomies, respectively (P-value: 0.895), while actuarial mean Disease Free Interval was 91 months (95%CI 82-100) and 96 months (95%CI 84-108) respectively (P-value: 0.565). We did not observe any difference in terms of local recurrence rate between the two groups (P = 0.337). CONCLUSIONS: Lingulectomy and trisegmentectomy lead to similar oncological outcomes compared to left upper lobectomy for T1 and T2 N0 NSCLC, and they could be used as an alternative to lobectomy even in patients with a good pulmonary function.

TNM Staging System in Thymoma: A Critical Appraisal?

Thymomas are rare tumors of the anterior mediastinum with peculiar clinical and pathological features. They have been deeply analyzed by pioneer authors, who strictly linked their name to the main pathological and staging classifications. Before the latest edition of the WHO classification of thymic epithelial tumors, the history of thymoma pathological classification inherited the name of the pathologists who systematically addressed the issue, from Levine-Rosai to Muller-Hermelink. Similarly, the thymoma staging system is intimately related to the name of two surgeons, Masaoka and Koga, who historically dealt with this disease. More recently, the traditional tumor-nodes-metastasis (TNM) system has been developed for the staging of this condition, in a rational attempt to put thymomas in conformity with the other solid tumors. The efforts of the International Thymic Malignancies Interest Group (ITMIG) and the Thymic Domain of the Staging and Prognostic Factors Committee (TD-SPFC) of the International Association for the Study of Lung Cancer (IASLC) resulted in the TNM classification of thymic tumors, which have been included in the eighth edition of the American Joint Committee on Cancer's (AJCC) Cancer Staging Manual. Herein, we report a narrative review of the evolution of the thymic epithelial tumors (TET) staging system and present a critical appraisal of the actual TNM classification compared with the historical Masaoka-Koga classification, with special focus on the proposal for the ninth edition of the TNM, expected in 2024.

Comparative analysis of genetic variants in pleural fluids and solid tissue biopsies of pleural mesothelioma patients: Implications for molecular heterogeneity assessment.

Objectives: This study aims to determine whether the sequencing of DNA extracted from pleural fluids (PFs) of Pleural Mesothelioma (PM) patients accurately represents the genetic information obtained from the solid tissue counterpart biopsies with particular attention to the identification of single nucleotide variants (SNVs). Materials and methods: Single pleural biopsy, PFs, and blood were collected from PM patients. DNA was extracted from these samples and then subjected to Whole-Exome Sequencing. Results: A higher number of SNVs was identified in PFs than in solid tissue biopsies (STBs). Most SNVs were detected in PFs samples but not in STBs samples, while only a few SNVs were detected in STBs samples but not in PFs samples. Conclusion: The current findings support the notion that PFs might offer a more robust depiction of cancer's molecular diversity. Nonetheless, the current outcomes challenge the assertion that liquid biopsies can encompass the entirety of intra-patient variations. Indeed, a subset of potential cancer-driver SNVs was exclusively identified in STBs. However, relying solely on STBs would have precluded the detection of significant SNVs that were exclusively present in PFs. This implies that while PFs serve as a valuable complement to STBs, they do not supplant them.

Lung Metastasectomy: Where Do We Stand? Results from an Italian Multicentric Prospective Database.

Background/Objectives: The surgical resection of pulmonary metastases is considered a therapeutic option in selected cases. In light of this, we present the results from a national multicenter prospective registry of lung metastasectomy. Methods: This retrospective analysis involves data collected prospectively and consecutively in a national multicentric Italian database, including patients who underwent lung metastasectomy. The primary endpoints were the analysis of morbidity and overall survival (OS), with secondary endpoints focusing on the analysis of potential risk factors affecting both morbidity and OS. Results: A total 470 lung procedures were performed (4 pneumonectomies, 46 lobectomies/bilobectomies, 13 segmentectomies and 407 wedge resections) on 461 patients (258 men and 203 women, mean age of 63.1 years). The majority of patients had metastases from colorectal cancer (45.8%). In most cases (63.6%), patients had only one lung metastasis. A minimally invasive approach was chosen in 143 cases (30.4%). The mean operative time was 118 min, with no reported deaths. Morbidity most frequently consisted of prolonged air leaking and bleeding, but no re-intervention was required. Statistical analysis revealed that morbidity was significantly affected by operative time and pulmonary comorbidities, while OS was significantly affected by disease-free interval (DFI) > 24 months (p = 0.005), epithelial histology (p = 0.001) and colorectal histology (p = 0.004) during univariate analysis. No significant correlation was found between OS and age, gender, surgical approach, surgical extent, surgical device, the number of resected metastases, lesion diameter, the site of lesions and nodal involvement. Multivariate analysis of OS confirmed that only epithelial histology and DFI were risk-factors, with p-values of 0.041 and 0.031, respectively. Conclusions: Lung metastasectomy appears to be a safe procedure, with acceptable morbidity, even with a minimally invasive approach. However, it remains a local treatment of a systemic disease. Therefore, careful attention should be paid to selecting patients who could truly benefit from surgical intervention.

Pathological T3 Non-Small Cell Lung Cancer with satellite nodules: Number or size, what does matter?

BACKGROUND: Non-small Cell Lung Cancer (NSCLC) with intralobar satellite nodule are defined as T3 (T3SN). We investigated the main features of these tumors and analyzed their impact on Overall Survival (OS). METHODS: This was a retrospective multicentric study including all pT3SN NSCLC operated on between 2005 and 2020, excluding patients with multifocal ground-glass opacities; who received induction therapies; N3 or stage IV. The diameter of largest (LgN) and smallest nodule (SmN), the total diameter (sum of diameter of all nodules, TS), and the number of SN were measured. RESULTS: Among 102 patients, 64.7 % were male. 84.3 % of patients had one SN (84.3 %), 9.8 % two SN while 5.9 % more than 2 SN. 63 patients were pN0. LgN (p = 0.001), SN (p = 0.005) and TS (p = 0.014) were significantly related to lymph-node metastasis; the LgN and TS were related to visceral pleural invasion (p < 0.001). Five-year OS was 65.1 %; at univariable analysis more than 2 satellite nodules, LgN and TS were significantly related to worse OS; at multivariable analysis, TS (Hazard Ratio [HR] 1.116 95 % Confidence Interval [CI] 1.008-1.235, p = 0.034) was an independent prognostic factors for OS. No significant prognostic factors were found for DFS at multivariable analysis. In pN0 patients, LgN (HR 1.051, 95 % CI 1.066-1.099, p = 0.027) and non-adenocarcinoma (HR 5.315 CI 95 % 1.494-18.910, p = 0.010) influenced OS. CONCLUSIONS: Tumor size is related to tumor's local invasiveness. TS is an independent prognostic factor for OS. Patients with more than 2 SN seem to be at higher risk for death and recurrence.

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.

Endobronchial ultrasound-transbronchial needle aspiration: effectiveness and accuracy in non-small cell lung cancer staging.

INTRODUCTION: Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) has a cardinal role in the diagnosis and staging of non-small cell lung cancer (NSCLC), providing an accurate nodal staging in a less invasive way than surgical biopsy. The aim of this study was to assess the diagnostic accuracy of EBUS-TBNA in the pre-operative NSCLC mediastinal staging, as well as to evaluate EBUS-TBNA specificity and sensibility in our cohort. METHODS: We retrospectively analyzed data of NSCLC patients who underwent EBUS-TBNA followed by major pulmonary resection between January 2020 and December 2022. EBUS-TBNA was performed in patients with NSCLC (central T ≤ 3 cm, peripheral/central T > 3 cm), following the ESTS guidelines. The target nodes were selected on the basis of their radiologic/metabolic characteristics. Each procedure was conducted together with rapid on-site cytological evaluation (ROSE). RESULTS: Twenty-five patients were included (M/F = 17/8). At least three needle passages on each target lymph node were performed. No complications during or after the procedures occurred. We found a 100% correspondence between ROSE on the sampled nodes and postoperative pathologic findings. An upstaging occurred in three cases (12%) because of the involvement of stations 5 and 6 (not accessible via EBUS), while the only case of downstaging (N2 → N0, 4%) was probably due to intercurrent neoadjuvant chemotherapy. In all cases, EBUS-TBNA has proved to achieve a diagnostic procedure on the target nodes. CONCLUSIONS: EBUS-TBNA is a safe and effective procedure that offers high sensitivity and specificity when performed together with ROSE, which improves the accuracy of sampling. Doubt on nodal stations 5 and 6 involvement should be settled by other techniques.

Early-Stage Non-Small Cell Lung Cancer: Prevalence of Actionable Alterations in a Monocentric Consecutive Cohort.

Early-stage (ES) non-small cell lung cancer (NSCLC) is diagnosed in about 30% of cases. The preferred treatment is surgery, but a significant proportion of patients experience recurrence. Neoadjuvant and adjuvant chemotherapy has a limited clinical benefit. EGFR tyrosine kinase inhibitors and immunotherapy have recently opened new therapeutic scenarios. However, only a few data are available about the ES-NSCLC molecular landscape and the impact of oncogene addiction on therapy definition. Here, we determined the prevalence of the main lung cancer driver alterations in a monocentric consecutive cohort. Molecular analysis was performed on 1122 cases, including 368 ES and 754 advanced NSCLC. The prevalence of actionable alterations was similar between early and advanced stages. ES-NSCLC was significantly enriched for MET exon-14 skipping alterations and presented a lower prevalence of BRAF p.(V600E) mutation. PD-L1 expression levels, evaluated according to actionable alterations, were higher in advanced than early tumors harboring EGFR, KRAS, MET alterations and gene fusions. Taken together, these results confirm the value of biomarker testing in ES-NSCLC. Although approved targeted therapies for ES-NSCLC are still limited, the identification of actionable alterations could improve patients' selection for immunotherapy, favoring the enrollment in clinical trials and allowing a faster treatment start at disease recurrence.

Intraoperative prevention and conservative management of postoperative prolonged air leak after lung resection: a systematic review.

Background: Prolonged air leak (PAL) due to an alveolar-pleural fistula (APF) is the most common complication after lung surgery. PAL is associated with an increased risk of morbidity and mortality, a longer chest tube duration, hence a prolonged hospitalization. Management of PAL may be challenging, and the thoracic surgeon should be aware of the possible therapeutic strategies. Methods: A systematic literature review was performed in PubMed, Cochrane Library, EMBASE, Ovid and Google Scholar. Title, abstract and full-text screening was performed, followed by structured data extraction, methodological quality assessment and Cochrane risk of bias assessment. Inclusion criteria were: case-control studies/randomized controlled trials (RCTs) comparing the new tested method with the standard of care to manage PAL after lung surgery; PAL due to APF; at least 10 patients; English-written papers. Results: A total of 942 initial papers from literature search, resulted in 43 papers after the selection. This systematic review found that the use of intraoperative measures as surgical sealants or pleural tenting, as well as a proper management of the chest drain and the use of blood patch or sclerosant agents seem to reduce postoperative air leaks incidence and/or duration and length of chest drain stay and hospitalization. Conclusions: Different measures have been described in literature to manage or prevent postoperative PAL. Most of them seem to be safe and efficient if compared to the "wait and see" strategy, even if large comparative studies that standardize the intra- and post-operative management of APF after lung resection are lacking and, actually, hard to conceptualize. However, there is a large consensus on the value of a preoperative PAL-risk stratification and on the necessity of tailoring PAL management or prevention's strategy and its timing on each patient's features.

Cold coagulation in thoracoscopic treatment of primary pneumothorax: a comparison with apicectomy.

OBJECTIVES: Primary spontaneous pneumothorax is a common disease, whose surgical treatment is still enigmatic in terms of timing and technique. Herein, we reported our experience with the parenchymal-sparing technique via cold coagulation (CC), in comparison to stapler apicectomy (SA). METHODS: We retrospectively collected data of all patients with apical blebs or <2 cm bullae treated with minimally invasive surgery for recurrent or persistent spontaneous pneumothorax, from 2010 to 2020. Two different surgical techniques were used: SA and the parenchymal-sparing CC of the apex. Perioperative and long-term results were analysed and compared. RESULTS: Out of 177 patients enrolled, 77 patients (CC group) underwent cold-coagulation of the apex while 100 patients (SA group) were treated with SA. Two groups were comparable in terms of age, surgical indication, intraoperative findings and affected side. CC group had a mean operative time of 43.2 min (standard deviation ± 19.5), shorter than SA group with 49.3 min (standard deviation ± 20.1, P-value: 0.050). Complication rate was significantly different between 2 groups, 5 (7%) and 16 (16%), for the CC and SA groups, respectively (P: 0.048), even if not in terms of prolonged postoperative air leak (P: 0.16). During the follow-up, 13 homolateral recurrences were reported: 2 (3%) in group CC and 11 (11%) in group SA; with a significant difference (P: 0.044). All reinterventions (postoperative prolonged air leak and recurrences) required an SA. CONCLUSIONS: Parenchymal-sparing technique through CC of apical blebs and bullae is an effective treatment for primary spontaneous pneumothorax and guarantees a good immediate lung sealing, despite stapling still represents the choice treatment in complex cases.

Surgical treatment of tracheal stenosis during Covid-19 era: a single-center experience and lessons learnt on the field.

SARS-CoV2 outbreak led to several healthcare system challenges, especially concerning respiratory support to Covid-19 patients. In the first 2 years of pandemic (2020-2021), we assisted to a marked increase of post-invasive mechanical ventilation (IMV) tracheal stenosis incidence, many of them requiring surgical treatment, namely resection and primary end-to-end anastomosis. Our aim is to describe our experience during the abovementioned biennium, focusing on postoperative outcomes of patients who have had Covid-19 ("post-Covid"). We retrospectively collected pre-, intra- and postoperative data on all patients who underwent tracheal surgery for benign stenosis in our Unit from May 2020 to October 2021, including previous Covid-19. Comparison between "post-Covid-19" and "non-Covid-19" groups' outcomes was then performed. Patients were 9 males and 6 females, and mean age was 57.4 ± 13.21 years. Nine patients had previous Covid-19 (60%). All patients underwent multidisciplinary preoperative evaluation. Almost every operation was conducted by cervicotomy, and the mean length of the resected specimen was 23.9 ± 6.5 mm. Postoperative complications were: dysphonia (3 cases), wound infection (1), bleeding (1), ab-ingestis pneumonia (1), anastomosis dehiscence (2), and stenosis recurrence (1). Thirty-day mortality rate was 6.7% (1 patient). No significant differences between "post-Covid-19" and "non-Covid-19" groups were identified. Pathology revealed, in 5 "post-Covid-19" patients, signs of vasculitis or perivascular inflammatory infiltrate. Tracheal stenosis' surgical treatment has always been known as a challenging procedure because of high perioperative morbidity and mortality rates. Our experience shows that previous Covid-19 and ongoing pandemic did not significantly affect perioperative outcomes of patients who underwent tracheal resection and primary end-to-end anastomosis in a high-volume Center and after multidisciplinary workup.

Unradical Surgery for Locally-Advanced Thymoma: Is it time to evolve Perspectives?

OBJECTIVES: Nearly-one-third of thymomas are locally-advanced at diagnosis. The traditional dogma that surgery is justified in case a complete resection can be achieved has remained unmovable until today. This study aimed to investigate feasibility and oncologic efficacy of incomplete resection for locally-advanced thymomas in a contest of multimodality therapy. MATERIALS AND METHODS: A retrospective analysis was conducted using data of prospectively maintained thymomas database in a single high-volume centre. Data on 285 consecutive patients undergoing surgery for stage III and IVa thymomas between 1995 and 2019 were reviewed. Patients who underwent incomplete resection with curative-intent (removal of at least 90% of tumour burden) were included. Long-term outcomes and predictors of cancer-specific survival (CSS) and progression-free survival (PFS) were analyzed. Secondary endpoint was to assess adjuvant therapy efficacy. RESULTS: The study included 79 patients, 60 with microscopic residual tumour (76%, R1) and 19 with macroscopic residual disease (24%, R2). Masaoka-Koga stage was: III in 41 patients (52%) and IVa in 38 (48%). Histology was B2-thymomas (n = 31, 39.2%) followed by B3 (n = 27, 34.2%). Five- and 10-years CSS was 88% and 80%. Seventy patients (90%) underwent adjuvant treatment; they showed CSS comparable to radical resected patients (5-years: 89.1% vs 98.9%, respectively; 10-years: 81.8% vs 92.7%, respectively, p = 0.43). The site of residual disease, Masaoka-Koga stage and WHO histology did not affect prognosis. Stepwise multivariable analysis confirmed adjuvant therapy as a favourable CSS prognostic factor (HR, 0.51; 95% CI, 0.33-0.79, p = 0.003). Stratifying by subgroups, R2-patients who received postoperative chemo(radio)therapy (pCRT) showed a significantly better prognosis than R2-patients treated by consolidation radiotherapy alone (10-years CSS: 60%, p < 0.001). CONCLUSION: In locally-advanced thymomas, whenever a radical surgery cannot be achieved, incomplete resection has proved to be effective in a contest of multimodality strategy, independently of WHO histology, Masaoka-Koga stage and site of residual disease.

Somatic mutations of thymic epithelial tumors with myasthenia gravis.

Background: Thymic epithelial tumors are rare malignant neoplasms that are frequently associated with paraneoplastic syndromes, especially myasthenia gravis. GTF2I is an oncogene mutated in a subgroup of thymomas that is reputed to drive their growth. However, for GTF2I wild-type tumors, the relevant mutations remain to be identified. Methods: We performed a meta-analysis and identified 4,208 mutations in 339 patients. We defined a panel of 63 genes frequently mutated in thymic epithelial tumors, which we used to design a custom assay for next-generation sequencing. We sequenced tumor DNA from 67 thymomas of patients with myasthenia gravis who underwent resection in our institution. Results: Among the 67 thymomas, there were 238 mutations, 83 of which were in coding sequences. There were 14 GTF2I mutations in 6 A, 5 AB, 2 B2 thymomas, and one in a thymoma with unspecified histology. No other oncogenes showed recurrent mutations, while sixteen tumor suppressor genes were predicted to be inactivated. Even with a dedicated assay for the identification of specific somatic mutations in thymic epithelial tumors, only GTF2I mutations were found to be significantly recurrent. Conclusion: Our evaluation provides insights into the mutational landscape of thymic epithelial tumors, identifies recurrent mutations in different histotypes, and describes the design and implementation of a custom panel for targeted resequencing. These findings contribute to a better understanding of the genetic basis of thymic epithelial tumors and may have implications for future research and treatment strategies.

Thymectomy in severe (Myasthenia Gravis Foundation of America classes IV-V) generalized myasthenia gravis: is the game really worth the candle?

OBJECTIVES: Total thymectomy in addition to medical treatment is an accepted standard therapy for myasthenia gravis (MG). Patients with severe generalized MG present life-threatening events, poor prognosis and higher risk of postoperative myasthenic crisis. The aim of our study is to investigate neurological and surgical results in patients with Myasthenia Gravis Foundation of America (MGFA) class IV and V MG following thymectomy. METHODS: Data on 76 MG patients with preoperative MGFA classes IV and V who underwent thymectomy were retrospectively collected. Primary end points included short-term surgical outcomes and long-term neurological results including the achievement of complete stable remission and any improvement as defined by MGFA Post-Intervention Status criteria. RESULTS: There were 27 (35.5%) males and 49 (64.5%) females; 53 (69.7%) were classified as MGFA class IV and 23 (30.3%) as class V. Thymectomy was performed through sternotomy in 25 (32.9%) patients, Video-assisted thoracic surgery (VATS) in 5 (6.6%) and Robot-assisted thoracic surgery (RATS) in 46 (60.5%). The median operative time was 120 (interquartile range: 95; 148) min. In-hospital mortality was observed in 1 (1.3%) patient and postoperative complications in 14 (18.4%) patients. The median postoperative hospital stay was 4 (interquartile range: 3; 6) days. Pathological examination revealed 31 (40.8%) thymic hyperplasia/other benign and 45 (59.2%) thymomas. Cumulative complete stable remission and improvement probabilities were 20.6% and 83.7% at 5 years and 66.9% and 97.6% at 10 years, respectively. A significant improvement rate was found in patients with age at the time of thymectomy of ≤50 years (P = 0.0236), MGFA class V (P = 0.0154) and acetylcholine receptor antibodies positivity (P = 0.0152). CONCLUSIONS: Thymectomy in patients with severe MG yields good perioperative outcomes and satisfactory long-term neurological improvement, especially for patients younger than 50 years, with MGFA class V and anti-AChR+ MG.