Malignant pleural mesothelioma (MPM) remains an incurable disease. This is partly due to the lack of experimental models that fully recapitulate the complexity and heterogeneity of MPM, a major challenge for therapeutic management of the disease. In addition, the contribution of the MPM microenvironment is relevant for the adaptive response to therapy. We established mesothelioma patient-derived organoid (mPDO) cultures from MPM pleural effusions and tested their response to pemetrexed and cisplatin. We aimed to evaluate the contribution of mesothelioma-associated fibroblasts (MAFs) to the response to pemetrexed and cisplatin (P+C). Organoid cultures were obtained from eight MPM patients using specific growth media and conditions to expand pleural effusion-derived cells. Flow cytometry was used to verify the similarity of the organoid cultures to the original samples. MAFs were isolated and co-cultured with mPDOs, and the addition of MAFs reduced the sensitivity of mPDOs to P+C. Organoid formation and expression of cancer stem cell markers such as ABCG2, NANOG, and CD44 were altered by conditioned media from treated MAFs. We identified IL-6 as the major contributor to the attenuated response to chemotherapy. IL-6 secretion by MAFs is correlated with increased resistance of mPDOs to pemetrexed and cisplatin.

Introduction: Bronchial carcinoid (BC) tumors represent between 1% and 5% of all lung cancers and about 20–30% of carcinoid tumors; they are classified into two groups: typical and atypical bronchial carcinoids. The aim of the present study was to review the results of endoscopic treatments as an alternative to surgical treatment in selected patients. Materials and methods: The present study was a retrospective and multicentric study, in which all data were reviewed for patients with BC in the central airways, referred to the Thoracic Surgery Units of Luigi Vanvitelli University of Naples and Sant’Andrea Hospital in Rome between October 2012 and December 2022 Overall, 35 patients, 13 of whom were female, were included in the study (median age, 53 years; range, 29–75 years). All patients underwent rigid bronchoscopy combined with flexible bronchoscopy. Tumor clearance was mostly performed by use of Argon Plasma Coagulation or Thulep Laser, mechanical debridement and excision with the use of forceps and aspirator through the working channel of the 8.5 mm-sized rigid bronchoscope. There were no complications during the treatment. Results: Endobronchial treatment provided complete tumor eradication in all patients; two patients had controlled bleeding complications; however, bleeding was well controlled without patient desaturation, and only one patient died of renal failure during the follow-up period. We found two recurrences in the left and right main bronchus, in patients with atypical carcinoma during fiberoptic bronchoscopy follow-up. Only one patient died of renal failure. At the first analysis, there were no significant differences between the patients receiving endobronchial treatment and patients receiving surgical treatment in the present study (p-value > 0.05—it means statistically insignificant). Conclusions: Endobronchial treatment is a valid and effective alternative for patients with BC unsuitable for surgery.

Patients with advanced lung cancer are candidates for systemic therapies. In the context of improved tumor responses and prolonged survival periods, the treatment of tumor/therapy‐related complications must be taken into account. Rescue surgery consists of a surgical resection without oncologic purpose but with the aim of controlling an acute and life‐threatening complication. We evaluated the postoperative outcomes of patients with advanced stage lung cancer who underwent rescue surgery for tumor or therapy‐related life‐threatening complications. We conducted a systematic review of literature using PubMed, Scopus, Embase, and Google Scholar using following keywords: (“rescue surgery” or “salvage surgery” or “salvage lung resection”) and (“lung cancer” or “non‐small cell lung cancer” or “NSCLC” or “SCLC”). The primary outcome was overall survival. Secondary outcomes were the morbidity and mortality. Nine articles were included in our review for a total of 64 patients. The most common indications for rescue surgery were lung abscess, post‐obstructive pneumonia, hemoptysis, and empyema. The lung resection consisted of lobectomy (n = 31, 48%), bilobectomy (n = 5, 8%), pneumonectomy (n = 11, 17%), sleeve pneumonectomy (n = 15, 23%), sleeve lobectomy (n = 1, 2%), and segmentectomy (n = 1, 2%). The mean overall survival was 12 months; the postoperative complication rate was 51%. No intraoperative deaths were observed. Rescue surgery is feasible for patients with advanced lung cancer and tumor/therapy‐related life‐threatening complications. Rescue surgery may allow access to ulterior systemic therapies; but the risk–benefit imbalance should always be taken into account, considering this as a last resort treatment.

Background. Malignant pleural mesothelioma (MPM) is still a rather incurable disease. Many classes of compounds with various mechanisms of action have been tested in vivo and ex-vivo, with rather disappointing results. This is partly due to preclinical studies mostly performed in models that fail to recapitulate MPM complexity and do not retain the intra-tumor heterogeneity, a propelling force for tumor progression. Additionally, we and others have shown that, under stress-induced chemotherapy, profound rearrangements take place in MPM cultures to fuel the emergence of chemoresistant cell subpopulations. Thus, finding clinically actionable modulators of MPM resistance is still a very urgent need. Methods. Setup and propagation of patient-derived organoid cultures from MPM pleural effusions; flow cytometry-based validation of organoid cultures, isola-tion and propagation of mesothelioma-associated fibroblasts; co-cultures, Lu-minex-based Cytokine array, ELISA assay to quantitate IL-6 in the conditioned media, qRT-PCR to assess mRNA expression of cancer stem cell markers and fibroblast markers. Results. Organoid cultures were obtained from eight MPM patients by using specific growth media and conditions to propagate pleural effusion-derived cells. We proved that primary MPM specimens and serially passaged (mesothelio-ma-Patient-Derived-Organoids) mPDOs were cytologically similar, with the obtained mPDOs expressing mesothelial markers similarly to the originating specimen. As expected from a clinically relevant model, the size and number of mPDOs were altered, in a patient-specific way, when pharmacologically relevant doses of chemotherapy drugs were added. We derived Mesothelio-ma-Associated-Fibroblasts (MAFs) and the addition of MAFs, to various ratios, altered the response of the mPDOs to pemetrexed + cisplatin, toward a reduced sensitivity to the latter anticancer agents. Additionally, organoid formation and size were altered by MAF-conditioned media, and this correlated with increased expression of cancer stem cell markers. We showed increased levels of IL-6 in the media of the treated cocultures and showed that this latter was derived from the MAFs. Conclusions. Increased secretion of IL-6 by mesothelioma-associated fibroblasts (MAFs) contributes to the resistance of the MPM to therapy.

Introduction: The mediastinum is a complex anatomical region that contains vital structures such as the great vessels, heart, esophagus, and trachea. Mediastinal masses include a wide range of lesions, both malignant and benign. Our study aimed to evaluate whether the combination of intraoperative ultrasound (IUS) and VATS can allow obtaining an adequate, correct, and safer diagnosis in patients with a mediastinal mass, especially in severely ill patients affected by heart failure, renal failure, advanced oncological stage, and respiratory failure.Material and Method: This single‐center, retrospective, observational study included 298 consecutive patients with mediastinal mass, evaluated between March 2018 and December 2024 at the Thoracic Surgery Department of Vanvitelli University of Naples. All patients underwent biopsies of mediastinal masses via VATS with IUS. Mediastinal masses were classified based on their ultrasound characteristics, allowing precise identification of the site and solid part of the lesions for biopsy. No significant complications were reported.Results: A total of 298 patients underwent VATS for mediastinal mass biopsy. About 185 of these patients underwent biopsies via VATS with IUS. All were under general anesthesia with single‐lung ventilation. A specific diagnosis was obtained in all patients who underwent biopsies via VATS with IUS (185/185), with lymphoma being the most common entity (58.6%), followed by germ cell tumors (24.3%) and thymic carcinoma (12.4%). A significant difference in diagnostic accuracy, specificity, and sensibility was found between the group that used IUS versus the group in which no IUS was used (100%vs. 93%, 99.8% vs. 94%, 98.5% vs. 90.5% respect).Conclusion: IUS‐guided biopsy allows for correct, safe, and precise identification of mediastinal lesions, establishing IUS as the “Gold Standard” for procedure guidance when the target lesion is adequately visualized.

Herein, we reported the damage of the B6 bronchial segment following apical segmentectomy of the left lower lobe for management of a typical carcinoid tumor. The defect was localized distally to the B6 origin and was successfully repaired by re‐stapling the proximal side of the B6 bronchus. Before firing, the intraoperative bronchoscopy confirmed the closure of the B6 bronchus alone and the normal patency of the bronchial pyramid basal. Then, the bronchial stump was covered by a collagen patch to reduce the risk of fistula. The postoperative course was uneventful, and the patient was discharged 3 days later.