Mesothelioma-Associated Fibroblasts Modulate the Response of Mesothelioma Patient-Derived Organoids to Chemotherapy via Interleukin-6.

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.

Multidisciplinary Management of Descending Necrotizing Mediastinitis: Is Thoracoscopic Treatment Feasible?

Background: Descending necrotizing mediastinitis (DNM) is a life-threatening condition, generally caused by downward dissemination of oropharyngeal infections through cervical fascial planes. Mediastinal drainage is conventionally achieved by thoracotomy, but a Video-Assisted Thoracoscopic Surgery (VATS) approach is gaining interest due to the reduced invasiveness of procedure. We aimed to evaluate the effectiveness of VATS treatment in patients with DNM. Methods: We conducted a retrospective multicenter study including patients with descending mediastinitis that underwent mediastinal drainage through VATS (VATS group) or thoracotomy (thoracotomy group), both in association with cervical drainage. Patients with mediastinitis secondary to cardiac, pulmonary, or esophageal surgery were excluded. The intergroup differences regarding surgical outcome and postoperative morbidity and mortality were compared. Results: A total of 21 patients were treated for descending mediastinitis during the study period. Cervicotomy and thoracotomy were performed in 15 patients (71%), while cervicotomy and VATS were performed in 6 patients (29%). There were no significant differences in surgical outcome, postoperative morbidity, and mortality between groups. VATS treatment was not associated with a higher complication rate. Patients in the VATS group had a shorter operative time (p = 0.016) and shorter ICU stay (p = 0.026). Conclusions: VATS treatment of DNM is safe and effective. The comparison with thoracotomy showed no significant differences in postoperative morbidity and mortality. The VATS approach is associated with a shorter operative time and ICU stay than thoracotomy.

Advances in Endoscopic Management of Endobronchial Carcinoid.

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.

Intraoperative lung ultrasound improves subcentimetric pulmonary nodule localization during VATS: Results of a retrospective analysis.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) resection of deep-seated lung nodules smaller than 1 cm is extremely challenging. Several methods have been proposed to overcome this limitation but with not neglectable complications. Intraoperative lung ultrasound (ILU) is the latest minimally invasive proposed technique. The aim of the current study was to analyze the accuracy and efficacy of ILU associated with VATS to visualize solitary and deep-seated pulmonary nodules smaller than 1 cm. METHODS: Patients with subcentimetric solitary and deep-seated pulmonary nodules were included in this retrospective study from November 2020 to December 2022. Patients who received VATS aided with ILU were considered as group A and patients who received conventional VATS as group B (control group). The rate of nodule identification and the time for localization with VATS alone and with VATS aided with ILU in each group were analyzed. RESULTS: A total of 43 patients received VATS aided with ILU (group A) and 31 patients received conventional VATS (group B). Mean operative time was lower in group A (p < 0.05). In group A all the nodules were correctly identified, while in group B in one case the localization failed. The time to identify the lesion was lower in group A (7.1 ± 2.2 vs. 13.8 ± 4.6; p < 0.05). During hospitalization three patients (6.5%; p < 0.05) in group B presented air leaks that were conservatively managed. CONCLUSION: Intracavitary VATS-US is a reliable, feasible, real-time and effective method of localization of parenchymal lung nodules during selected wedge resection procedures.