Transcriptional perturbation of protein arginine methyltransferase-5 exhibits MTAP-selective oncosuppression.

We hypothesized that small molecule transcriptional perturbation could be harnessed to target a cellular dependency involving protein arginine methyltransferase 5 (PRMT5) in the context of methylthioadenosine phosphorylase (MTAP) deletion, seen frequently in malignant pleural mesothelioma (MPM). Here we show, that MTAP deletion is negatively prognostic in MPM. In vitro, the off-patent antibiotic Quinacrine efficiently suppressed PRMT5 transcription, causing chromatin remodelling with reduced global histone H4 symmetrical demethylation.

MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial.

Introduction: One of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL.

Extended pleurectomy decortication: the current role.

Extended pleurectomy/decortication (EPD) has been formally defined but there remain technical areas of debate between practitioners. This is partly attributable to the relative rarity of this operation which is largely confined to a small number of specialist centres. Nevertheless, there is a widespread acceptance that extended pleurectomy/decortication (P/D) is a realistic and favourable alternative to extrapleural pneumonectomy.

Surgical management of lung cancer with multiple lesions: implication of the new recommendations of the 8 edition of the TNM classification for lung cancer.

The 8 tumour, node and metastasis (TNM) revision of the staging classification for lung cancer has attempted to clarify the different properties of four distinct clinical presentations: synchronous multiple primary lung cancers; primary tumour with intrapulmonary metastases; pneumonic-type adenocarcinoma and multiple ground glass/lepidic lesions. The respective biological profiles determine different surgical strategies for each category. Accurate preoperative histological confirmation is required to identify synchronous primary tumours which should then be managed as two separate episodes within the confines of patient characteristics.

Loss of functional BAP1 augments sensitivity to TRAIL in cancer cells.

Malignant mesothelioma (MM) is poorly responsive to systemic cytotoxic chemotherapy and invariably fatal. Here we describe a screen of 94 drugs in 15 exome-sequenced MM lines and the discovery of a subset defined by loss of function of the nuclear deubiquitinase BRCA associated protein-1 (BAP1) that demonstrate heightened sensitivity to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand). This association is observed across human early passage MM cultures, mouse xenografts and human tumour explants.

Video assisted thoracoscopic and open chest surgery in diagnosis and treatment of malignant pleural diseases.

Parenchymal cancers of lung, breast, gastrointestinal tract and ovaries as well as lymphomas and mesotheliomas are among the most common cancer types causing malignant effusions, though almost all tumour types have been reported to cause a malignant effusion. The prognosis heavily depends on patients' response to systemic therapy however, regardless of the causing pathology and histopathologic form, malignant pleural disease is normally associated with a poor prognosis. To date, there are not sufficient data to allow accurate predictions of survival that would facilitate decision making for managing patients with malignant pleural diseases.

VATS and open chest surgery in diagnosis and treatment of benign pleural diseases.

A negative pressure normally exists between the visceral and parietal pleurae in the lungs, which can act as vacuum for fluid, air and small particles from different parts of the body, allowing them to move into the pleural space and be retained in it, thus resulting to different manifestations of pleural disorders. A pleural effusion is the result of fluid collection between the parietal and visceral pleural surfaces. The most common cause in developed countries is congestive heart failure, followed by pneumonia and malignancy.

Extended pleurectomy decortication for malignant pleural mesothelioma in the elderly: the need for an inclusive yet selective approach.

Objectives: The median age at diagnosis of patients with pleural mesothelioma in the UK is 73 years. Recent series have shown the feasibility of extended pleurectomy decortication in the elderly, but with continuing debate about the efficacy of this treatment, we reviewed our experience to identify more detailed selection criteria.

Methods: We reviewed prospectively collected data on all patients from 1999 to 2016 undergoing extended pleurectomy decortication.

Hybrid bilobectomy for treatment of an early-stage lung cancer in a patient with severe emphysema using the benefits of lung volume reduction.

Patients with resectable lung cancer and concomitant emphysema can fall outside the accepted guidelines for surgery. Lung volume reduction can improve their lung function but involves resecting an emphysematous lobe containing the tumour. Volume reduction can also be achieved by endobronchial one-way valve insertion, causing lobar collapse, but intact fissures are required.

Long-term survival and symptomatic relief in lower lobe lung volume reduction surgery.

Objectives: Lung volume reduction surgery (LVRS) has been demonstrated to provide symptomatic relief and improve lung function in patients with end-stage emphysema. The National Emphysema Treatment Trial specifically noted functional benefits in patients with predominantly upper lobe emphysema and demonstrated improvement in quality-of-life parameters, in patients with non-upper lobe emphysema and a low-baseline exercise capacity. We aimed to investigate whether physiological and health status benefits correlated with lower lobe LVRS.

Is a diagnostic video-assisted thoracoscopic thymectomy an acceptable first-line approach to the suspicious anterior mediastinal mass?

Introduction: The incidental early-stage thymic mass presents a diagnostic challenge. Video-assisted thoracoscopic (VAT) thymectomy is an attractive but potentially morbid solution. The aim was to show it can be safely applied as a first-line modality in those with undiagnosed thymic enlargement with acceptable long-term results.

Randomized controlled trials in malignant pleural mesothelioma surgery-mistakes made and lessons learned.

Randomized surgical trials are of the most difficult to design and recruit, however, they are the only robust method available to establish a new surgical procedure. Mesothelioma is a disease with a perceived poor prognosis for which surgical intervention has relatively high complications and not insignificant mortality. This review will consider the mesothelioma and radical surgery (MARS) 1 and 2 trials, SAKK 17/04 trial and the EORTC 1205 trial all aimed at assessing the potential benefit of radical surgery for malignant pleural mesothelioma.

Surgery as part of radical treatment for malignant pleural mesothelioma.

Purpose Of Review: To review the latest developments in surgery for malignant pleural mesothelioma both in patient selection, surgical technique, and strategy.

Recent Findings: The International Association for the Study of Lung Cancer mesothelioma staging project has produced data to inform the 8th tumour node metastasis revision. The difficulty in clinical N staging and clinical T staging are highlighted and the importance of tumour volume is recognized.

Individualised risk in patients undergoing lung volume reduction surgery: the Glenfield BFG score.

Lung volume reduction surgery (LVRS) has been shown to be beneficial in patients with chronic obstructive pulmonary disease, but there is low uptake, partly due to perceived concerns of high operative mortality. We aimed to develop an individualised risk score following LVRS.This was a cohort study of patients undergoing LVRS.

If Background Lung Abnormalities Do Not Affect the Presentation of Spontaneous Pneumothorax, Is Lung Resection Always Justified?

Background: The suggestion that spontaneous pneumothorax (SP) may result from diffuse porosity rather than discrete anatomic abnormality challenges the practice of targeted bullectomy. We assessed whether underlying pulmonary abnormalities are correlated or could be predicted from the mode of presentation, with potential implications for treatment.

Methods: We analyzed 192 consecutive video-assisted thoracoscopic surgery resections for SP (139 primary, 53 secondary) in 171 patients (115 male, age 36, range, 16 to 81).

How does the timing of chemotherapy affect outcome following radical surgery for malignant pleural mesothelioma?

Objectives: There is little evidence regarding the use of chemotherapy as part of multimodality treatment of malignant pleural mesothelioma (MPM). We aimed to determine whether, in those patients fit for chemotherapy, a delay in this treatment affected survival.

Materials And Methods: We analysed postoperative variables of 229 patients undergoing either extrapleural pneumonectomy (EPP) (81 patients) or extended pleurectomy-decortication (EPD) (197 patients) for MPM at a single centre.

The role of thoracic surgery in the management of mesothelioma: an expert opinion on the limited evidence.

Surgery has a key role at different points in the management of Malignant Pleural Mesothelioma. Diagnosis with video assisted thoracoscopy offers excellent sensitivity and specificity and a direct view of the pleural cavity to verify the extent of the tumor. Nodal involvement can be assessed by mediastinoscopy and either talc pleurodesis or partial pleurectomy can be used for symptom control in advanced stage disease.

The management of the diaphragm during radical surgery for malignant pleural mesothelioma.

Objectives: Macroscopic complete resection with lung preservation is the objective of radical management of pleural mesothelioma (MPM). Total removal of visceral and parietal pleura (pleurectomy/decortication) almost invariably proceeds to an extended pleurectomy/decortication (EPD) to ensure macroscopic complete resection. We suspected this may not always be necessary.