BAP1 loss induces mitotic defects in mesothelioma cells through BRCA1-dependent and independent mechanisms.

The tumour suppressor BRCA1-associated protein 1 (BAP1) is the most frequently mutated cancer gene in mesothelioma. Here we report novel functions for BAP1 in mitotic progression highlighting the relationship between BAP1 and control of genome stability in mesothelioma cells with therapeutic implications. Depletion of BAP1 protein induced proteasome-mediated degradation of BRCA1 in mesothelioma cells while loss of BAP1 correlated with BRCA1 loss in mesothelioma patient tumour samples.

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.

Abemaciclib in patients with p16ink4A-deficient mesothelioma (MiST2): a single-arm, open-label, phase 2 trial.

Background: Genetically stratified therapy for malignant mesothelioma is unavailable. Mesotheliomas frequently harbour loss of the chromosome 9p21.3 locus (CDKN2A-MTAP), which is associated with shorter overall survival due to loss of the tumour suppressor p16ink4A, an endogenous suppressor of cyclin-dependent kinase (CDK)4 and CDK6.

True thymic hyperplasia causing pure red cell aplasia: a case report.

Pure red cell aplasia caused by true thymic hyperplasia is extremely rare. We report the case of a 25-year-old female diagnosed with pure red cell aplasia. Following a thymectomy confirming true thymic hyperplasia and corticosteroid therapy, complete response was achieved.

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.

Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment.

Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20-50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort.

Metastatic renal cell carcinoma extending to the left atrium through the inferior pulmonary vein.

Metastatic renal cell carcinoma with involvement through the pulmonary veins to the left atrium is very rare. We report the case of a 70-year-old male with metastatic renal cell carcinoma to the right lower lobe of the lung abutting the inferior pulmonary vein with extension to the left atrium without pre-operative evidence. Surgical resection was achieved through a posterolateral thoracotomy.

Rucaparib in patients with BAP1-deficient or BRCA1-deficient mesothelioma (MiST1): an open-label, single-arm, phase 2a clinical trial.

Background: Malignant mesothelioma remains an incurable cancer, with no effective treatments in the setting of relapsed disease. Homologous recombination deficiency predicts sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. In mesothelioma, BRCA1-associated protein 1 carboxy-terminal hydrolase (BAP1), which regulates DNA repair, is frequently mutated.

BRCA1/MAD2L1 Deficiency Disrupts the Spindle Assembly Checkpoint to Confer Vinorelbine Resistance in Mesothelioma.

Mesothelioma is a universally lethal cancer lacking effective therapy. The spindle poison vinorelbine exhibits clinical activity in the relapsed setting, and in preclinical models requires to initiate apoptosis. However, the mechanisms underlying this regulation and the clinical implications have not been explored.

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.

Trifecta St. Jude medical® aortic valve in pulmonary position.

: To evaluate an aortic pericardial valve for pulmonary valve (PV) regurgitation after repair of congenital heart defects. : From July 2012 to June 2016 71 patients, mean age 24 ± 13 years (four to years) underwent PV implantation of aortic pericardial valve, mean interval after previous repair = 21 ± 10 years (two to 47 years). Previous surgery at mean age 3.

Body Mass Index and Mortality Among Adults Undergoing Cardiac Surgery: A Nationwide Study With a Systematic Review and Meta-Analysis.

Background: In an apparent paradox, morbidity and mortality are lower in obese patients undergoing cardiac surgery, although the nature of this association is unclear. We sought to determine whether the obesity paradox observed in cardiac surgery is attributable to reverse epidemiology, bias, or confounding.

Methods: Data from the National Adult Cardiac Surgery registry for all cardiac surgical procedures performed between April 2002 and March 2013 were extracted.

Does the placement of an Amplatzer septal occluder device confer benefit in patients with a post-infarction ventricular septal defect?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Is the placement of an Amplatzer septal occluder device across a post-infarction ventricular septal defect a suitable alternative for patients not eligible for surgical repair?' Altogether, 31 papers were found using the reported search, of which 17 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated.

Hypoplastic internal carotid artery stenosis with a low-lying carotid bifurcation causing cerebral ischemia.

Congenital abnormalities of the internal carotid artery (ICA) are infrequent and can be associated with aberrations of the Circle of Willis. A 47-year-old gentleman presented with transient neurological symptoms and cerebral infarction and carotid Doppler showed a stenotic right ICA. Subsequent computed tomographic angiography showed a hypoplastic ICA with a low-lying bifurcation at the C6 level and aplasia of the anterior communicating artery.

Does knee replacement surgery lead to chronic limb ischemia?

Total knee replacement (TKR) may be associated with chronic limb ischemia (CLI) due to arterial injury intraoperatively. The aim of this study was to determine the incidence of CLI after TKR surgery. Patients who received a unilateral TKR in 2003-2004 were identified from our database.

In patients coming to theatre with an intra aortic balloon pump, is it better to turn it off or keep it on while on bypass?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'In patients coming to theatre with an intra aortic balloon pump (IABP), is it better to turn it off or keep it on while on bypass?' Altogether 46 papers were found using the reported search, of which 11 represented the best evidence to answer the clinical question. Nine of them were randomised controlled trials (RCTs).

Should you place one or two chest drains in patients undergoing lobectomy?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Should you place one or two chest drains in patients undergoing lobectomy?' Altogether >200 papers were found using the reported search, of which six represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated.

Should patients undergoing cardiac surgery with atrial fibrillation have left atrial appendage exclusion?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Should patients undergoing cardiac surgery with atrial fibrillation (AF) have left atrial appendage (LAA) exclusion?' Altogether 310 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated.