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Objectives: This study aimed to evaluate the predictive and prognostic factors in clinical stage I, ALK-rearranged lung adenocarcinoma following radical surgery. Additionally, it sought to compare these factors with an external cohort of ALK wild-type patients., Methods: A multicentric, retrospective, case control analysis was conducted on patients with clinical T1-2 N0 ALK-rearranged lung adenocarcinoma who underwent anatomical resection and radical lymphadenectomy. Data were collected from five high-volume oncological centers. An external cohort of ALK wild type patients was also analyzed for comparison. Survival analyses were performed using the Kaplan-Meier method, and multivariable Cox regression analysis was used to identify prognostic factors., Results: From January 2016 to December 2022, 63 patients with ALK-rearranged lung adenocarcinoma were included. High-grade tumors (G3) significantly associated with upstaging (OR = 3.904, p = 0.04). DFS and OS were significantly improved in upstaged patients receiving adjuvant treatment (HR = 0.18, p = 0.0042; HR = 0.24, p = 0.0004, respectively). The solid or micropapillary histological subtypes were independently associated with worse DFS (HR = 3.41, p = 0.022). Comparison with 435 ALK WT patients showed worse DFS in the ALK-rearranged group (HR = 2.09, p = 0.0003). ALK-rearranged patients had higher rates of nodal upstaging, systemic, and brain recurrences., Conclusions: Clinical T1-2 N0 ALK-rearranged lung adenocarcinoma is an aggressive disease with a specific tropism for lymph nodes and the brain. High-grade tumors are predictive of nodal upstaging. Adjuvant treatment significantly improves DFS and OS in upstaged patients, highlighting the need for personalized preoperative staging and post-surgical management in this cohort., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Asthma management often includes inhaled corticosteroids (ICSs), with additional controllers like long-acting muscarinic antagonists (LAMAs) for severe cases. The primary goal of this study was to investigate the pharmacological interaction between various concentrations of fluticasone furoate (FF) and umeclidinium (UME) in isolated human airways to determine the nature of their interaction, whether synergistic or additive. Medium bronchi and small airways obtained from patients undergoing lobectomy were passively sensitized to mimic asthmatic conditions. The effects of FF and UME, alone and in combination, on airway relaxation were evaluated using histamine-induced contraction and electrical field stimulation. Pharmacological interactions were analyzed using the Bliss Independence theory. Results indicated that FF induced a partial, concentration-dependent relaxation of sensitized airways, while UME induced a larger relaxation in medium bronchi but a weaker effect in small airways. The combination of FF and UME resulted in significantly greater relaxation than either drug alone, demonstrating synergism at high concentrations in medium bronchi but only additive effects in small airways. This study suggests that higher doses of FF might be necessary in a fixed dose combination to achieve optimal synergistic bronchodilation with UME. Future research should focus on clinical trials to confirm these findings and explore the molecular mechanisms underlying these interactions, potentially improving personalized asthma therapy., Competing Interests: Declaration of competing interest MGM participated as a faculty member and advisor in scientific meetings and courses under the sponsorship of ABC Farmaceutici, Almirall, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline and Novartis, was a consultant to Chiesi Farmaceutici and GSK, and her department was funded by GSK and Novartis. LC has participated as advisor in scientific meetings under the sponsorship of Boehringer Ingelheim and Novartis, received nonfinancial support from AstraZeneca, received a research grant partially funded by Chiesi Farmaceutici, Boehringer Ingelheim, Novartis, and Almirall; has been a consultant to ABC Farmaceutici, Edmond Pharma, Zambon, Verona Pharma, and Ockham Biotech; his department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis, and Zambon. MC participated as a faculty member and advisor in scientific meetings and courses under the sponsorship of Abdi Ibrahim, Alkem, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Cipla, Eurodrug, GSK, Glenmark, Lallemand, Mankind Pharma, Menarini Group, Mundipharma, Novartis, Pfizer, Recipharm, Sanofi, Teva, Verona Pharma and Zambon, and was a consultant to ABC Farmaceutici, AstraZeneca, Chiesi Farmaceutici, GSK, Lallemand, Novartis, Ockham Biotech, Recipharm, Verona Pharma and Zambon. PR has participated as a faculty member and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma, Novartis, Recipharm, Sanofi, and Zambon, and her department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis, and Zambon. CP is a consultant to Eurodrug, Recipharm, Ananda Developments and Microa, and has equity in Verona Pharma. BR, CB, FF and FTG declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

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., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background and Aim: Lipoma is a benign mesenchymal tumor. It is a very common tumor and in 13% of cases occurs in head and neck. Giant lipomas are extraordinary and cervical involvement with mediastinal extension is an exceedingly rare presentation. Only a few cases of thoracic extension are reported in literature., Methods: We describe the case of a 62-years-old man with a giant cervico-mediastinic lipoma which required a combined approach through cervicotomy and sternotomy to ensure surgical radicality. Differential diagnoses could be thymolipoma, liposarcoma or familiar lipomatosis., Results: The mass was removed en-bloc with thymus and locoregional lymph nodes. The patient recovered uneventfully., Conclusions: The aim of this report is to discuss potential pitfalls of differential diagnosis and implementation of the therapeutic treatment. Focus on the relevance of performing fluorescence in situ hybridization (FISH) for MDM2 amplification is reported, a necessary technique for the differential diagnosis. (www.actabiomedica.it).