Cytoreductive surgery with hyperthermic intrathoracic chemotherapy for malignant pleural mesothelioma: a systematic review.

INTRODUCTION: Cytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that remains will lead to disease progression in the majority of patients. Delivery of hyperthermic intrathoracic chemotherapy at the time of surgery has been used to address this microscopic disease, however it's effect and place in the multimodality treatment sphere is unknown. The aim of this systematic review was to assess the effect of surgery and hyperthermic intrathoracic chemotherapy in patients with MPM on overall survival and disease-free interval. METHODS: Ovid MEDLINE, Embase, Web of Science and the Cochrane Database of Systematic Reviews were searched from database inception through to June 2021. Studies reporting overall survival and/or disease-free interval in patients with MPM undergoing cytoreductive surgery with hyperthermic intrathoracic chemotherapy were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A narrative review was performed. RESULTS: Fifteen studies were eligible for inclusion comprising 598 patients. Surgery with hyperthermic intrathoracic chemotherapy was associated with a median overall survival and disease-free interval ranging from 11 to 75 months and 7.2 to 57 months, respectively. These appeared to be superior to patients not receiving hyperthermic intrathoracic chemotherapy (overall survival: 5-36 months and disease-free interval: 12.1-21 months). A higher dose of hyperthermic intrathoracic chemotherapy was associated with an improvement in overall survival compared with a lower dose: 18-31 months versus 6-18 months, respectively. The most common morbidity was atrial fibrillation followed by renal complications. CONCLUSION: Surgery with hyperthermic intrathoracic chemotherapy offers a safe and effective therapy with an improvement in disease-free interval and overall survival, particularly when hyperthermic intrathoracic chemotherapy is administered at a higher dose. PROSPERO REGISTRATION NUMBER: CRD42019129002.

A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma.

Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68+ monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8+ T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68+ monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.

The impact of perioperative non-steroidal anti-inflammatory drugs use on pleurodesis following thoracic surgery.

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: in patients who have had {visceral and parietal pleural symphysis}, {do NSAIDs reduce} {the efficacy of pleurodesis}? Sixteen papers were discovered in the search. Of these, 3 human studies were included in the analysis. None showed a significantly higher rate of pleurodesis failure in patients given perioperative NSAIDs. The results from the largest study met criteria for noninferiority. Within the constraints of the study, the results suggest that systemic administration of nonsteroidal anti-inflammatory medication in the perioperative period does not necessarily attenuate effective pleurodesis. However, further study is needed as there is a clear paucity of human-based studies.

The chicken or the egg? A case of sympathetic staphylococcal empyema thoracis and splenic abscess.

Multicavitary abscesses are uncommon in immunocompetent individuals. Splenic abscesses being relatively uncommon with an incidence of 0.1-0.7% in quoted series [ 1]. Commonly reported cases are secondary infective endocarditis. To have both a splenic abscess and empyema concurrently is rare. We describe a case of a patient with a large left-sided empyema thoracis and concurrent splenic abscess.

Uniportal VATS retrieval of an endobronchial coil migrated through pericardium.

Endobronchial insertion of nitinol coils is a minimally invasive treatment strategy for selected patients with advanced emphysema. Although coil migration into the pleural space has been described by Marchetti et al. (Endobronchial coil penetration into the pleural space. Thorax 2018;73:890-1) [ 1], breach through the pericardium has not been reported to date.