ERS International Congress 2023: highlights from the Thoracic Surgery and Lung Transplantation Assembly.

Five sessions presented at the European Respiratory Society Congress 2023 were selected by Assembly 8, consisting of thoracic surgeons and lung transplant professionals. Highlights covering management of adult spontaneous pneumothorax, malignant pleural effusion, infectious and immune-mediated complications after lung transplantation, as well as the pro and con debate on age limit in lung transplantation and results of the ScanCLAD study were summarised by early career members, supervised by the assembly faculty.

Second Surgery for Recurrent Malignant Pleural Mesothelioma after Multimodality Treatment: A Systematic Review.

Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumour with poor prognosis. To date, a multimodality treatment, including chemotherapy and surgery, with or without radiotherapy, is the gold standard therapy for selected patients with epithelioid and early-stage MPM. In this setting, the goal of surgery is to achieve the macroscopic complete resection, obtained by either extrapleural pneumonectomy or pleurectomy/decortication. Failure, in local and/or distant sites, is one of the major concerns; in fact, there has been no established treatment for the recurrence of MPM after the multimodal approach, and the role of surgery in this context is still controversial. By using electronic databases, studies that included recurrent MPM patients who underwent a second surgery were identified. The endpoints included were: a pattern of recurrence, post-recurrence survival (PRS), and the type of second surgery. When available, factors predicting better PRS and perioperative mortality and morbidity were collected. This systematic review offers an overview of the results that are currently obtained in patients undergoing a second surgery for relapsed MPM, with the aim to provide a comprehensive view on this subject that explores if a second surgery leads to an improvement in survival.

Computed Tomography and Spirometry Can Predict Unresectability in Malignant Pleural Mesothelioma.

Preoperative identification of unresectable pleural mesothelioma could spare unnecessary surgical intervention and accelerate the initiation of medical treatments. The aim of this study is to determine predictors of unresectability, testing our impression that the contraction of the ipsilateral hemithorax is often associated with exploratory thoracotomy. Between 1994 and 2020, 291 patients undergoing intended macroscopic complete resection for mesothelioma after chemotherapy were retrospectively investigated. Eligible patients (n = 58) presented a preoperative 3 mm slice-thickness chest computed tomography without pleural effusion or hydropneumothorax. Lung volumes (segmented using a semi-automated method), modified-Response Evaluation Criteria in Solid Tumors (RECIST) measurements, and spirometries were collected after chemotherapy. Multivariable analysis was performed to determine the predictors of unresectability. An unresectable disease was found at the time of operation in 25.9% cases. By multivariable analysis, the total lung capacity (p = 0.03) and the disease burden (p = 0.02) were found to be predictors of unresectability; cut-off values were <77.5% and >120.5 mm, respectively. Lung volumes were not confirmed to be associated with unresectability at multivariable analysis, probably due to the correlation with the disease burden (p < 0.001; r = -0.4). Our study suggests that disease burden and total lung capacity could predict MPM unresectability, helping surgeons in recommending surgery or not in a multimodality setting.

Relapse Patterns and Tailored Treatment Strategies for Malignant Pleural Mesothelioma Recurrence after Multimodality Therapy.

To date, there have been no established therapies for recurrent malignant pleural mesothelioma (MPM) after multimodality treatment. Aims of this retrospective study are to analyze the recurrence pattern, its treatment and to identify the predictors of best oncological outcomes for relapsed MPM, comparing extrapleural pneumonectomy (EPP) vs. pleurectomy/decortication (PD). Study population: 94 patients with recurrence of MPM after multimodality treatment underwent macroscopic complete resection (52.1% with EPP and 47.9% with PD) between July 1994 and February 2020. Distant spread was the most frequent pattern of recurrence (71.3%), mostly in the EPP group, while the PD group showed a higher local-only failure rate. Post-recurrence treatment was administered in 86.2%, whereas best supportive care was administered in 13.8%. Median post-recurrence survival (PRS) was 12 months (EPP 14 vs. PD 8 months, p = 0.4338). At multivariate analysis, predictors of best PRS were epithelial histology (p = 0.026, HR 0.491, IC95% 0.263-0.916), local failure (p = 0.027, HR 0.707, IC95% 0.521-0.961), DFS ≥ 12 months (p = 0.006, HR 0.298, IC95% 0.137-0.812) and post-recurrence medical treatment (p = 0.046, HR 0.101, IC95% 0.897-0.936). The type of surgical intervention seems not to influence the PRS if patients are fit enough to face post-recurrence treatments. In patients with a prolonged disease-free interval, in the case of recurrence the most appropriate treatment seems to be the systemic medical therapy, even in the case of local-only relapse.

ECLS for Life-Threatening Complications in Mesothelioma Surgery: Is It Worthwhile?

Extracorporeal life support (ECLS) is an effective method for bridging patients to recovery in cases of respiratory and/or cardiac failure that are potentially reversible and unresponsive to conventional management. Nevertheless, there have been only few reports about the use of ECLS in oncological patients with complications due to their neoplasm or its treatment. We report the use of veno-arterial extracorporeal membrane oxygenation in three cases of severe perioperative complications following surgery for mesothelioma after induction chemotherapy at our Institution.

VATS right basal segmentectomy for NSCLC in a patient with systemic sclerosis.

In recent decades, the thoracoscopic approach has been accepted as the gold standard to treat early stage non-small-cell lung cancer because it reduces postoperative pain and results in a shorter hospital stay. More recently, several techniques for performing sublobar resection have been reported that achieve a radical resection while sparing as much parenchyma as possible.  This video tutorial illustrates our technique for resecting the basal segments of the right lower lobe in a patient presenting with an adenocarcinoma in the right lower lobe. The patient also had systemic sclerosis, which led to pulmonary hypertension and fibrosis. Therefore, it was important to limit the parenchymal resection to save the apical segment of the lower lobe so as not to exacerbate the underlying conditions. The vascular and bronchial structures are readily identifiable, and the intersegmental plane can be easily accessed by clamping the associated bronchus while inflating the lung.

Use of a reabsorbable patch as tracheal substitute in a complicated urgent tracheostomy.

Airway dehiscence after tracheal resection-anastomosis is a major complication that often requires an urgent reoperation. If ischaemia of the airway is extensive, however, performing a tracheostomy might be complicated. Here, we describe the case of a patient who underwent urgent tracheostomy because of acute airway dehiscence, wherein an absorbable prosthesis was used to repair the defect of the anterior trachea.

Human Papilloma Virus Increases ΔNp63α Expression in Head and Neck Squamous Cell Carcinoma.

P63, and in particular the most expressed ΔNp63α isoform, seems to have a critical role in the outcome of head and neck cancer. Many studies have been conducted to assess the possible use of p63 as a prognostic marker in squamous cell carcinoma cancers, but the results are still not well-defined. Moreover, a clear relationship between the expression of ΔNp63α and the presence of high-risk HPV E6 and E7 oncoproteins has been delineated. Here we describe how ΔNp63α is mostly expressed in HPV-positive compared to HPV-negative head and neck cancer cell lines, with a very good correlation between ΔNp63α mRNA and protein levels.

Extrapleural pneumonectomies for pleural mesothelioma.

Introduction: Malignant pleural mesothelioma (MPM) is a fatal malignancy for which there is no definitive cure. The most effective multimodality treatment in prolonging survival is still matter of debate. Surgery remains one of the cornerstones in the multimodality therapy for MPM. Extra-pleural pneumonectomy and pleurectomy/decortication are the two main curative-intent procedures; however, the superiority of one technique over the other is still debated. This review aims to assess short- and long-term results of extrapleural pneumonectomy for MPM.Areas covered: This article focuses on the role of extrapleural pneumonectomy in MPM. A systematic review was performed by using electronic databases to identify studies that included patients treated by this procedure for MPM. Endpoints included overall survival, disease-free survival, recurrence rate, perioperative mortality, and morbidity.Expert commentary: This paper offers an overview of the results that are currently obtained in patients undergoing extrapleural pneumonectomy for MPM. The benefit of surgical treatments in MPM is still debated and its primary goal should be the achievement of a macroscopic complete resection. Several alternative multimodality protocols exist, with specific advantages and drawbacks; therefore, individualization of care for each patient is fundamental. The complexity of the surgical treatment mandates that patients be referred to specialized centers.

Complex Lobectomy in a Patient With Lung Cancer and Pulmonary Artery Sling.

Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.

Intraoperative extracorporeal carbon dioxide removal support for minimally invasive surgical treatment of vanishing lung syndrome.

Vanishing lung syndrome is a rare disease that could be treated successfully in selected cases with bullectomy. Protective ventilation is very important during surgery to achieve optimal post-operative results and to prevent complications. Hypercapnia and respiratory acidosis are the main disadvantages of this ventilator strategy. The use of extracorporeal CO2 removal device has been introduced to support protective and ultra-protective ventilation during respiratory failure in complex cases. In thoracic surgery the intraoperative use of this device is still not widespread. We report a successful case of a giant left lung bullectomy with intraoperative support with Pro-Lung CO2 removal device for the management of hypercapnia during single lung ventilation.

Predictors of behaviour in solitary fibrous tumours of the pleura surgically resected: Analysis of 107 patients.

OBJECTIVES: Gold standard therapy for solitary fibrous tumour of the pleura is complete surgical resection. Aims of this retrospective study are to evaluate oncological and surgical outcomes and to verify the clinical reliability of prognostic scores presented in literature. METHODS: Study population: 107 patients surgically treated between 1972 and 2018. Male/female ratio: 1/2.45; median age at surgery: 60 years (range, 19-80); peduncle lesions 69.8%; visceral pleura origin 72.9%; benign histology 73.8%; median diameter 8 cm (range 1 to 35, 27 cases giant [≥15 cm]). RESULTS: After a median follow up of 7 years, 12 patients had recurrence. By multivariate analysis, malignant histology (P = .03; HR, 4.17; 95% CI, 1.15-15.06), origin from parietal pleura (P = .03; HR, 3.90; 95% CI, 1.08-14.09), England (P = .002; HR, 1.98; 95% CI, 1.28-3.07), Diebold (P = .008; HR, 1.96; 95% CI, 1.20-3.22) and Tapias (P = .003; HR, 1.75; 95% CI, 1.20-2.53) scores were found independent significant predictors of relapse. Giant tumours were associated with open surgery (P = .003), origin from parietal pleura (P = .011) and intraoperative bleeding (P > .001). Overall 10-year disease-free survival (DFS) rate was 81%. Predictors of worst DFS were parietal pleura origin (P = .002), malignant histology (P = .006) and all the prognostic scores. CONCLUSIONS: Malignant histology and origin from parietal pleura were significant predictors of tumour recurrence and worst DFS. The use of current scoring systems can help to predict clinical behaviour. Patients with higher risk of relapse can benefit from closer follow up, prolonged over 10 years.

Synergistic antitumour activity of HDAC inhibitor SAHA and EGFR inhibitor gefitinib in head and neck cancer: a key role for ΔNp63α.

BACKGROUND: Epidermal growth factor receptor (EGFR) overexpression is associated with the development of head and neck cancer (HNC) and represents one of the main therapeutic targets for this disease. The use of EGFR inhibitors has limited efficacy due to their primary and acquired resistance, partially because of increased epithelial to mesenchymal transition (EMT). The HDAC inhibitor SAHA has been shown to revert EMT in different tumours, including HNC. In this study, we investigated the cooperative role of SAHA and the EGFR tyrosine kinase inhibitor gefitinib in both HPV-positive and HPV-negative HNC cell lines. METHODS: A panel of 12 HPV-positive and HPV-negative HNC cell lines were screened for cell viability upon treatment with SAHA, gefitinib and the combination of the two. Epithelial/mesenchymal marker expression, as well as activation of signalling pathway, were assessed upon SAHA treatment. ΔNp63α silencing with shRNA lentiviral particles was used to determine its role in cell proliferation, migration and TGFß pathway activation. RESULTS: We found that both SAHA and gefitinib have antitumour activity in both HPV-positive and HPV-negative HNC cell lines and that their combination has a synergistic effect in inhibiting cell growth. SAHA treatment reverts EMT and inhibits the expression of the transcription factor ΔNp63α. Suppression of ΔNp63α reduces EGFR protein levels and decreases cell proliferation and TGFß-dependent migration in both HPV-positive and HPV-negative HNC cell lines. CONCLUSIONS: Our results, by giving a clear molecular mechanism at the basis of the antitumour activity of SAHA in HNC cell lines, provide a rationale for the clinical evaluation of SAHA in combination with gefitinib in both HPV-positive and HPV-negative HNC patients. Further knowledge is key to devising additional lines of combinatorial treatment strategies for this disease.

Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.