Annabel J. Sharkey

The effects of an intentional transition from extrapleural pneumonectomy to extended pleurectomy/decortication.

OBJECTIVES For many years, extrapleural pneumonectomy (EPP) was the operation of choice for the radical management of pleural mesothelioma in the UK. However, doubts surrounding the efficacy of EPP, and the change in demographics of the affected population, have prompted a transition in our practice towards extended pleurectomy/decortication (EPD). The aim of this study was to determine the effects an intentional transition from EPP to EPD has had on patient outcome. METHODS Data from 362 patients undergoing radical surgery (229 EPD, 133 EPP) during 1999-2014 were included. Demographics and outcome were compared between the two groups; EPP versus EPD. RESULTS The median age of patients undergoing EPD was significantly higher than those undergoing EPP [57 years (range 14-70 years) vs 65 years (range 42-81 years), P < 0.001]. There was a significantly higher proportion of patients with performance status ≥1 in the EPD group (46.3 vs 35.4%, P = 0.047). There was no difference in the median length of hospital stay between the two groups [14 days (range 1-133 days) vs 13 days (range 0-93 days), P = 0.409]. There was also no difference between the groups in terms of in-hospital mortality (EPP 5.3% and EPD 6.6%, P = 0.389), 30-day mortality [EPP 8 (6.0%) and EPD 8 (3.5%), P = 0.294] or 90-day mortality [EPP 18 (13.5%) and EPD 21 (9.2%), P = 0.220]. There was a significantly higher early reoperation rate in the EPP group (15.0 vs 6.2%, P = 0.008) but a significantly higher late reoperation rate in the EPD group (0.8 vs 5.3%, P = 0.037). There was no significant difference in overall survival or disease-free interval between the two groups (P = 0.899 and P = 0.399, respectively). However, overall survival was significantly greater in patients over the age of 65 undergoing EPD (12.5 vs 4.7 months, P = 0.001). CONCLUSION The transition from EPP to EPD in our standard practice has enabled us to operate on more elderly, frail patients with no significant increase in use of hospital resources, and without detriment to overall survival.

The use of extracorporeal membrane oxygenation in neonates with severe congenital diaphragmatic hernia: a 26-year experience from a tertiary centre†.

OBJECTIVES Neonates with severe congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation (ECMO) have a high rate of mortality. There is controversy regarding optimal time of surgical intervention. We present our data over a 26‐year period. METHODS We analysed data from our Extracorporeal Life Support Organization registry forms between 1989 and 2015, in order to determine the factors affecting survival outcome for repair of congenital diaphragmatic hernia with ECMO as a bridge to surgery and/or recovery. RESULTS Ninety‐eight neonates with congenital diaphragmatic hernia requiring ECMO were identified. In‐hospital mortality was 32%. The overall mortality (47.9%) in our study was seen up to 7 months, after this point there was no mortality. There was no difference in survival in patients repaired using pre‐, intra‐ or postoperative ECMO (P = 0.65). Requiring haemofiltration at any point was significantly associated with reduced survival [hazard ratio 2.7 (95% confidence interval 1.5‐4.9); P = 0.01] as was the presence of neurological complications [hazard ratio 3.7 (95% confidence interval 1.6‐8.5); P = 0.003]. Age, Apgar score, mode of delivery, side, associated cardiac comorbidities, pH, partial pressure of carbon dioxide, partial pressure of oxygen, oxygen saturations, bicarbonate, high‐frequency oscillatory ventilation, mode of ECMO, inhaled nitric oxide, pulmonary complications and bleeding were not associated with any survival difference. CONCLUSIONS We believe that all neonates with severe diaphragmatic hernia should be given the option of ECMO if clinically indicated. Provided these patients survive the initial postoperative period, they go on to have a sustained survival benefit. Long‐term cost analysis and morbidity need to be taken into account to determine the true effect of ECMO on congenital diaphragmatic hernia.

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. METHODS We reviewed 314 patients, 86.0% male, median age 62 years (range 14-81 years) undergoing radical surgery for MPM from 1999 to 2014, by either EPD or extrapleural pneumonectomy. The extent of diaphragmatic muscle involvement was recorded from postoperative pathology. Patients were divided into three groups: no involvement, non-transmural, transmural diaphragmatic invasion. RESULTS A total of 213 (68%) patients underwent EPD, 237 (75.5%) had epithelioid disease and 57.6% were node positive. There was no difference between the three groups in terms of age, cell type, laterality, neoadjuvant chemotherapy and operation. There was a higher degree of diaphragm involvement in females (P = 0.01) and in patients with positive lymph nodes (P = 0.01). No evidence of diaphragmatic involvement was found following pathological assessment of the resection specimen in 119 patients (37.9%). The incidence of abdominal disease progression was 23.9%. There was no correlation with degree of diaphragmatic invasion (ρ = 0.01 P = 0.88). Overall survival of those with abdominal progression was similar to those with progression elsewhere: 14.5 vs 13.0 months (P = 0.79), and with those with no progression (16.7 months, P = 0.189). There was no difference in survival when stratified by diaphragmatic involvement (P = 0.44). CONCLUSIONS In our cohort, there was no evidence of diaphragmatic invasion in over 30% of patients, and we have also failed to find evidence that peritoneal disease progression affects overall survival following radical management. It may therefore theoretically be unnecessary to resect the diaphragm in all cases, and a pleurectomy-decortication could suffice. However, there is an unknown risk of R2 resection which would prejudice survival, and as such we would advocate resecting the diaphragm in all cases to avoid an R2 resection.

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. We demonstrate that BAP1 deubiquitinase activity and its association with ASXL1 to form the Polycomb repressive deubiquitinase complex (PR-DUB) impacts TRAIL sensitivity implicating transcriptional modulation as an underlying mechanism. Death receptor agonists are well-tolerated anti-cancer agents demonstrating limited therapeutic benefit in trials without a targeting biomarker. We identify BAP1 loss-of-function mutations, which are frequent in MM, as a potential genomic stratification tool for TRAIL sensitivity with immediate and actionable therapeutic implications.

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). Presentation was categorized as: recurrent never drained (RND), recurrent drained, persistent air leak (PAL). Resected lung pathology was categorized as: no bleb/bulla, ruptured bleb/bulla, unruptured bleb/bulla. Results: No correlation between presentation and resected lung pathology was observed for primary (P=0.608) or secondary SP (P=0.597). A similar proportion of patients in each pathologic group presented with PAL or RND; ruptured bleb/bulla or no bleb/bulla was equally noted in PAL and RND group. Conclusions: There is lack of association between resected lung pathology and mode of presentation. This suggests that discrete anatomic abnormalities may not be responsible for the air leak leading to pneumothorax. In conjunction with favorable reported outcomes from medical thoracoscopy and talc pleurodesis alone, these findings challenge the current practice of routine video-assisted thoracoscopic surgery lung resection in these patients.

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. METHODS A retrospective analysis was performed from our prospectively collected patient database. A total of 36 patients with severe, non-upper lobe predominant emphysema underwent lower lobe LVRS in our institution, over a 20-year period. The assessments consisted of measurements of body mass index, pulmonary function tests and health-related quality of life using the Short Form 36-item questionnaires. RESULTS Forced expiratory volume in 1 s was seen to improve 3 months [coefficient of time = 1.55 (0.88, 2.21); P < 0.0001] after the procedure, maintained until the first 6 months [0.48 (0.12, 0.85); P = 0.010], decline over the second half of the first year and gradually return to preoperative levels after 2 years, while residual volume to total lung capacity (%) ratio was seen to follow a similar pattern with significant decrease from baseline after 3 months [coefficient of time = -1.76 (-2.75, -0.76); P = 0.001] and 6 months [-1.05 (-1.51, -0.59); P < 0.0001]. Quality-of-life improvements were mainly noted in physical components. CONCLUSIONS Contrary to a widely held misconception following the National Emphysema Treatment Trial that lower lobe lung volume reduction does not offer significant benefits to patients with non-upper lobe predominant emphysema, we feel justified in offering lower lobe LVRS in these patients when they meet the same selection criteria as upper lobe LVRS.

P161 HOW HAS THE SURGICAL TREATMENT OF LUNG CANCER IN THE UK EVOLVED OVER THE LAST TWO DECADES? – An illustrative surgeon’s experience

Background/introduction The practice of lung cancer surgery in UK has seen many changes over the last 20 years, with innovations in surgical technique and investigatory modalities together with significant organisational changes. Aims/objectives To assess how these changes have impacted on an individual Consultant surgical practice spanning this era. Method We have retrospectively reviewed a single-surgeon practice from consultant appointment to the present (1997–2015) comprising 1708 consecutive lung cancer operations: 962 (56%) lobectomy, 296 (17%) sublobar resection, 250 (15%) extended resection, 157 (9%) pneumonectomy, 43 (3%) open/close. Concurrently, 710 surgical staging procedures were performed. We analysed trends with time in type of procedure; open/close rates and in-hospital mortality. Results 1557 anatomic resections were performed (87 cases/year, 67–130) with no significant decrease in the annual workload. There were significant changes in the types of surgical procedures performed over the time period: a significant decrease in pneumonectomy rate (p < 0.001), mirrored by an increasing use of sleeve-resections (p = 0.088); an increase in the proportion of anatomical resections by video assisted thoracic surgery (VATS) (p < 0.001), an overall increasing number of anatomical segmentectomies (p < 0.001), with a stable rate of wedge resections (mean 6.3%, p = 0.908). There has been a significant decrease in surgical mediastinal staging, particularly after 2010 (p < 0.001) with a significant reduction in the open/close rate, particularly after 2004 (4.8 vs. 0.65%, p < 0.001). Overall the in-hospital mortality rate has significantly decreased (from 7.1% in 1998 to 2.9% in 2015, p = 0.004).Abstract P161 Figure 1 Conclusion There has been significant evolution in lung cancer surgery over the last two decades, which are illustrated in this individual surgeon’s practice. Whilst increased surgical experience may partly explain the changes, other important factors include: a change in the biology of lung cancer from central squamous to peripheral adenocarcinomas with earlier tumour detection, facilitating more VATS and lung-sparing surgery; improved perioperative care and the use of lesser resections, reducing mortality; and new techniques in staging (CT-PET, EBUS) reducing the need for surgical staging and the number of futile thoracotomies.