Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

BACKGROUND: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. METHODS: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. FINDINGS: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. INTERPRETATION: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. FUNDING: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).

Early Video-assisted Thoracoscopic Surgery or Intrapleural Enzyme Therapy in Pleural Infection: A Feasibility Randomized Controlled Trial. The Third Multicenter Intrapleural Sepsis Trial-MIST-3.

Rationale: Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). Objectives: To establish the feasibility of randomization in a surgery-versus-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. Methods: The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Measurements and Main Results: Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively (P = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) (P = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) (P = 0.023). One serious adverse event was reported in the VATS arm. Conclusions: This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).

Multidisciplinary paper on patient blood management in cardiothoracic surgery in the UK: perspectives on practice during COVID-19.

The coronavirus (COVID-19) pandemic disrupted all surgical specialties significantly and exerted additional pressures on the overburdened United Kingdom (UK) National Health Service. Healthcare professionals in the UK have had to adapt their practice. In particular, surgeons have faced organisational and technical challenges treating patients who carried higher risks, were more urgent and could not wait for prehabilitation or optimisation before their intervention. Furthermore, there were implications for blood transfusion with uncertain patterns of demand, reductions in donations and loss of crucial staff because of sickness and public health restrictions. Previous guidelines have attempted to address the control of bleeding and its consequences after cardiothoracic surgery, but there have been no targeted recommendations in light of the recent COVID-19 challenges. In this context, and with a focus on the perioperative period, an expert multidisciplinary Task Force reviewed the impact of bleeding in cardiothoracic surgery, explored different aspects of patient blood management with a focus on the use of haemostats as adjuncts to conventional surgical techniques and proposed best practice recommendations in the UK.

Lung volume reduction surgery versus endobronchial valves: a randomised controlled trial.

BACKGROUND: Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. METHODS: This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. RESULTS: 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 versus BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) versus BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm. CONCLUSION: Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.

The John S. Najarian symposium: The past, present, and future of surgery and transplantation, May 20, 2022, Minneapolis, MN.

Dr John S Najarian (1927-2020), chairman of the Department of Surgery at the University of Minnesota from 1967 to 1993, was a pioneer in surgery, clinical immunology and transplantation. A Covid-delayed Festschrift was held in his honor on May 20, 2022. The speakers reflected on his myriad contributions to surgery, transplantation, and resident/fellow training, as well as current areas of ongoing research to improve clinical outcomes. Of note, Dr Najarian was a founder of the journal Clinical Transplantation.

Is there an ideal position and size of chest drain following anatomical lung resection?

BACKGROUND: Chest drains are placed after surgery to enable lung re-expansion. However, there remains little guidance on optimal placement. This study aims to identify the ideal size and position for chest drain insertion with regards to post-operative outcomes. METHODS: 383 patients undergoing lobectomy in 1-year had their chest drain size and x-ray position noted (1 (apical), 2 (mid-zone) or 3 (basal)). Primary outcome was residual air space on immediate post-operative x-ray. Secondary outcomes were length of drain in situ (<72 versus ≥72 h), persisting pleural effusion, surgical emphysema, post-operative pneumonia (POP), and length of hospital stay (<5 versus ≥5 days). Fisher's exact analysis for the primary outcome and binary logistic regression analysis for all outcomes were used. Results presented as odds ratios (OR±95%CI). RESULTS: Univariate analysis for residual air space showed increased risk in area 2 (OR = 1.61, p = 0.041) and 3 (OR = 2.59, p = 0.0043) compared with area 1. Multivariate analysis for residual air space showed increased risk in area 2 (OR = 2.39, p < 0.001) and 3 (OR = 2.86, p < 0.001) compared with area 1. Drain size had no impact on residual air space in univariate or multivariate analysis. Multivariate analysis showed area 2 drains remained in situ for >72 h (OR = 1.49, p = 0.017), had persisting effusions (OR = 2.03, p = 0.004) and POP (OR = 2.10, p = 0.023) compared with area 1. This risk is magnified further for drains in area 3. Drains ≥28F had reduced risk of surgical emphysema (OR = 0.23, p = 0.027) in multivariate analysis. CONCLUSION: A ≥28F, apical chest drain reduces the risk of post-operative complications, allowing early removal and discharge.

Exploration for olive fruit fly parasitoids across Africa reveals regional distributions and dominance of closely associated parasitoids.

The olive fruit fly, Bactrocera oleae, has been a key pest of olives in Europe and North America. We conducted the largest exploration for parasitoids associated with the fly across Sub-Saharan Africa (Kenya, Namibia, and South Africa) including some of the fly's adjoining regions (Canary Islands, Morocco, Réunion Island and Tunisia). From Sub-Saharan regions, four braconids were collected: Bracon celer, Psytallia humilis, P. lounsburyi, and Utetes africanus. Results showed that their regional dominance was related to climate niches, with P. humilis dominant in hot semi-arid areas of Namibia, P. lounsburyi dominant in more tropical areas of Kenya, and U. africanus prevalent in Mediterranean climates of South Africa. Psytallia concolor was found in the Canary Islands, Morocco and Tunisian, and the Afrotropical braconid Diachasmimorpha sp. near fullawayi on Réunion Island. Furthermore, we monitored the seasonal dynamics of the fly and parasitoids in Cape Province of South Africa. Results showed that fruit maturity, seasonal variations in climates and interspecific interactions shape the local parasitoid diversity that contribute to the low fly populations. The results are discussed with regard to ecological adaptations of closely associated parasitoids, and how their adaptations impact biocontrol.

A fair CoP? MRF sampling, testing and reporting: Big problems caused by small particles. Part 2: Operational realities and financial implications.

The operation of qualifying materials recovery facilities (MRFs) in England is governed by the MRF code of practice (MRF CoP), which mandates certain sampling and testing practices for the mixed wastes being processed by the MRF. The results of this testing are required to be reported to the system regulator and are then made publicly available in a register. The MRF CoP is critically examined and certain aspects of the testing methodology are shown to be invalid, resulting in inaccurate information being included in the register. The current investigation looks at the extent of these inaccuracies and shows how they have very real financial implications for commercial operators of MRFs, especially where 'shared basket' contracts have been entered into, typically with local authorities.

A fair CoP? MRF sampling, testing and reporting: Big problems caused by small particles. Part 1: Compliance difficulties and data validity.

The Regulations governing Materials Recovery Facilities (MRFs) in England require that they report on the quality of both the incoming mixed wastes and the single-stream recyclate products, with the results being made available on a public register. In this investigation, tests were conducted on a number of mixed wastes from different suppliers being processed at a qualifying MRF to evaluate how effective the Regulations (or MRF Code of Practice (MRF CoP)) were in generating useful, meaningful information. The empirical evidence obtained showed that MRF CoP in its current form has a number of serious flaws which detract from the validity and value of the reported operational data. The statutory definition of 'material particles' in the mixed wastes given in the MRF CoP means that compliance with the MRF CoP is impracticable, and in order to overcome this it will be necessary to re-word the definition of 'material particles'. Empirical evidence also invalidated the explicit assumption made in the MRF CoP that the composition of the material particles is identical to that of the bulk materials, and consequently the basis for the mandatory apportioning of the weight of the material particles has no logical foundation and apportioning leads to distortion in the reported data. Changes will be required to the present statutory requirements for reporting operational results if the recorded information is to have meaning and relevance for stakeholders in the system.

Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma.

INTRODUCTION: Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left. METHODS AND ANALYSIS: The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery-(extended) pleurectomy decortication-versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment. ETHICS AND DISSEMINATION: Research ethics approval was granted by London - Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: ISRCTN-ISRCTN44351742 and ClinicalTrials.gov-NCT02040272.

The progression of non-small cell lung cancer from diagnosis to surgery.

OBJECTIVES: The IASLC 8th TNM Staging 8th differentiates between a greater number of T-stages. Resection remains the mainstay of curative treatment with often significant waiting times. This study aims to quantify the T-stage progression and growth of non-small cell lung cancers (NSCLCs) between radiological diagnosis and resection, and its impact on disease recurrence and survival. MATERIALS AND METHODS: A retrospective analysis of NSCLC resections (289) in a high-volume centre between July 01, 2015 and June 30, 2016. Baseline demographics, time from diagnostic CT to surgery, tumour size (cm) and T-stage from diagnostic CT, PET-CT and post-operative histopathology reports were recorded. The primary outcome was increase in T-stage from diagnostic CT to resection. Kaplan-Meier and cox proportional hazard analyses were used to determine recurrence-free survival and survival. RESULTS: Median increase in tumour size between diagnosis and resection was 0.3 cm (p < 0.0001). Median percentage increase in size was 13%. T-stage increased in 133 (46.0%) patients. N stage increased in 51 patients (17.7%), 32 (11.1%) to N2 disease. Mean survival in those upstaged was 43.5 (39.9-47.1) months versus 53.4 (50.0-56.8) months in patients not upstaged (p = 0.025). Mean recurrence-free survival in those upstaged was 39.1 (35.2-43.0) months versus 47.7 (43.9-51.4) months in patients not upstaged (p = 0.117). Upstaging was independently associated with inferior survival (HR 1.674, p = 0.006) and inferior recurrence-free survival (HR 1.423, p = 0.038). CONCLUSIONS: A significant number of patients are upstaged between diagnostic and resection resulting in reduced survival and recurrence-free survival. A change in management pathways are required to improve outcomes in NSCLC.

Case presentations and recommendations from the 2018 ITMIG Annual Meeting.

The 9th International Thymic Malignancy Interest Group's (ITMIG) Annual Meeting was held in Seoul, South Korea in October 2018, and in this article, we discuss three of the cases presented and review the radiology imaging and pathology slides. The first two cases involve thymic carcinoma: the first reviews systemic therapy recommendations for non-resectable recurrence and the second case the optimal treatment recommendations after incomplete resection. The third case discusses treatment recommendations for recurrent thymoma after complete resection.

Venous thromboembolism prophylaxis in thoracic surgery patients: an international survey.

OBJECTIVES: Venous thromboembolic events (VTE) after thoracic surgery (TS) can be prevented with mechanical and chemical prophylaxis. Unlike other surgical specialties, TS lacks evidence-based guidelines. In the process of developing these guidelines, an understanding of the current prophylaxis methods practiced internationally is necessary and is described in this article. METHODS: A 26-item survey was distributed to members of the European Society of Thoracic Surgeons (ESTS), American Association of Thoracic Surgery (AATS), Japanese Association for Chest Surgery (JACS) and Chinese Society for Thoracic and Cardiovascular Surgery (CSTCS) electronically or in person. Participants were asked to report their current prophylaxis selection, timing of initiation and duration of prophylaxis, perceived risk factors and the presence and adherence to institutional VTE guidelines for patients undergoing TS for malignancies. RESULTS: In total, 1613 surgeons anonymously completed the survey with an overall 36% response rate. Respondents were senior surgeons working in large academic hospitals (≥70%, respectively). More than 83.5% of ESTS, AATS and JACS respondents report formal TS thromboprophylaxis protocols in their institutions, but 53% of CSTCS members report not having such a protocol. The regions varied in the approaches utilized for VTE prophylaxis, the timing of initiation perioperatively and the use and type of extended prophylaxis. Respondents reported that multiple risk factors and sources of information impact their VTE prophylaxis decision-making processes, and these factors vastly diverge regionally. CONCLUSIONS: There is little agreement internationally on the optimal approach to thromboprophylaxis in the TS population, and guidelines will be helpful and vastly welcomed.

International Delphi survey of the ESTS/AATS/ISTH task force on venous thromboembolism prophylaxis in thoracic surgery: the role of extended post-discharge prophylaxis.

OBJECTIVES: Venous thromboembolic events can be successfully prevented with chemical and/or mechanical prophylaxis measures, but evidence-based guidelines in thoracic surgery are limited, particularly regarding extended post-discharge prophylaxis. This study attempts to gather an international consensus on best practices to inform the development of such guidelines. METHODS: A series of 3 surveys was distributed to the ESTS/AATS/ISTH (European Society of Thoracic Surgeons, American Association of Thoracic Surgeons, International Society for Thrombosis and Haemostasis) venous thromboembolic events prophylaxis working group starting January 2017. This iterative Delphi consensus process sought to gather a consensus on (i) risk factors; (ii) preferred agents; (iii) duration; and (iv) perceived barriers to an extended thromboprophylaxis approach. Participant responses were expressed on a 10-point scale, and the results were summarized and circulated to all respondents in subsequent rounds. A coefficient of variance of ≤0.3 was identified pre hoc to identify agreement. RESULTS: A total of 21 Working Group members completed the surveys, composed of 19% non-surgeon thrombosis experts, and 48% from North America. Respondents largely saw agreement regarding risk factors that indicate a need for extended thromboprophylaxis. The group agreed that low-molecular-weight heparin is a suitable agent for use post-discharge, but there was a wide variety in response regarding agents, duration and barriers to extended prophylaxis, where no consensus was observed across the three rounds. CONCLUSIONS: There is strong agreement around indications for extended venous thromboembolic events thromboprophylaxis after thoracic surgery, but there is little consensus regarding the agents and duration to be employed. Further research is required to better inform guideline development.

The right ventricular response to lung resection.

OBJECTIVES: Lung cancer is a leading cause of cancer death and in suitable cases the best chance of cure is offered by surgery. Lung resection is associated with significant postoperative cardiorespiratory morbidity, with dyspnea and reduced functional capacity as dominant features. These changes are poorly associated with deterioration in pulmonary function and a potential role of right ventricular (RV) dysfunction has been hypothesized. Cardiovascular magnetic resonance imaging is a reference method for noninvasive assessment of RV function and has not previously been applied to this population. METHODS: We used cardiovascular magnetic resonance imaging to assess the RV response to lung resection. Cardiovascular magnetic resonance imaging with volume and flow analysis was performed on 27 patients preoperatively, on postoperative day 2 and at 2 months. Left ventricular ejection fraction and RV ejection fraction, the ratio of stroke volume to end systolic volume, pulmonary artery acceleration time, and distensibility of main and branch pulmonary arteries were studied. RESULTS: Mean ± standard deviation RV ejection fraction deteriorated from 50.5% ± 6.9% preoperatively to 45.6% ± 4.5% on postoperative day 2 and remained depressed at 44.9% ± 7.7% by 2 months (P = .003). The ratio of stroke volume to end systolic volume deteriorated from median 1.0 (quartile 1, quartile 3: 0.9, 1.2) preoperatively to median 0.8 (quartile 1, quartile 3: 0.7, 1.0) on postoperative day 2 (P = .011). On postoperative day 2 there was a decrease in pulmonary artery acceleration time and operative pulmonary artery distensibility (P < .030 for both). There were no changes in left ventricular ejection fraction during the study period (P = .621). CONCLUSIONS: These findings suggest RV dysfunction occurs following lung resection and persists 2 months after surgery. The deterioration in the ratio of stroke volume to end systolic volume suggests a mismatch between afterload and contractility. There is an increase in indices of pulsatile afterload resulting from the operative pulmonary artery.

B-type natriuretic peptide predicts deterioration in functional capacity following lung resection.

OBJECTIVES: Following lung resection, there is a decrease in the functional capacity and quality of life, which is not fully explained by changes in pulmonary function. Previous work demonstrates that B-type natriuretic peptide (BNP) is associated with short- and long-term complications following lung resection, leading to the suggestion that cardiac dysfunction may contribute to functional deterioration. Our aim was to investigate any relationship between BNP and subjective and objective indices of functional deterioration following lung resection surgery. METHODS: Twenty-seven patients undergoing lung resection had serum BNP measured preoperatively, on postoperative day (POD)1 and POD2, and at 2 months postoperatively. The functional deterioration was assessed using 6-min walk tests and the Medical Research Council dyspnoea scale. 'Deterioration in functional capacity' was defined as either an increase in the Medical Research Council dyspnoea score or a significant decrease in the 6-min walk test distance. RESULTS: BNP increased over time (P < 0.01) and was significantly elevated on POD1 and POD2 (P < 0.02 for both). Seventeen patients demonstrated functional deterioration 2 months postoperatively. At all perioperative time points, BNP was significantly higher in patients showing deterioration (P < 0.05 for all). Preoperative BNP was predictive of functional deterioration at 2 months with an area under the receiver-operating characteristic curve of 0.82 (P = 0.01, 95% confidence interval 0.65-0.99). CONCLUSIONS: This study has demonstrated, using subjective and objective measures, that preoperative BNP is a predictor of functional deterioration following lung resection. BNP may have a role in preoperative risk stratification in this population, allowing therapy in future to be targeted towards high-risk patients with the aim of preventing postoperative cardiac dysfunction. CLINICAL TRIAL REGISTRATION NUMBER: NCT01892800.

The incidence of non-melanoma skin cancer and post-transplant lympho-proliferative disorders in the Scottish cardiac transplant population and the provision of specialist dermatological follow-up.

Background Immunosuppression helps prevent acute rejection post-cardiac transplant but has been linked to malignancy development. This may be due to a reduction in T-lymphocyte function, a direct oncogenic effect or the increased impact of environmental carcinogens. There has been shown to be significant increases in non-melanoma skin cancers and post-transplant lympho-proliferative disorders, particularly in those treated with OKT3. Aim To investigate the survival and incidence of malignancy in the Scottish cardiac transplant population and whether rates of non-melanoma skin cancers justify the provision of specialist dermatological follow-up. Methods and results Retrospective case note analysis of patients transplanted (363) or followed up (2) in Scotland from 1992 to 2016. Kaplan-Meier survival analysis generated a survival curve. Patients had a 1-year survival of 82% and a median survival of 10.9 years. There were 60 (95% CI 47.5, 75.2) NMSCs and 8 (3.7, 12.4) post-transplant lympho-proliferative disorders diagnosed in the cohort (3110 person years follow-up). Fisher's exact test was employed to analyse the association between induction therapy (via OKT3 or rabbit antithymocyte globulin) and post-transplant lympho-proliferative disorder development. Patients treated with OKT3 had a 6.7 times greater risk ( P = 0.014) and a shorter experience of patients treated with rabbit antithymocyte globulin has so far shown no significantly altered risk ( P = 1.00) of developing a post-transplant lympho-proliferative disorder. Conclusion Incidences of non-melanoma skin cancers and post-transplant lympho-proliferative disorders were increased in the Scottish cardiac transplant population and there was a significant association between post-transplant lympho-proliferative disorder development and OKT3 therapy but not rabbit antithymocyte globulin therapy. These findings in Scottish patients reflect what is published in wider literature and support the provision of a dedicated post-transplant dermatology clinic.

A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (TRANSFORM).

RATIONALE: Single-center randomized controlled trials of the Zephyr endobronchial valve (EBV) treatment have demonstrated benefit in severe heterogeneous emphysema. This is the first multicenter study evaluating this treatment approach. OBJECTIVES: To evaluate the efficacy and safety of Zephyr EBVs in patients with heterogeneous emphysema and absence of collateral ventilation. METHODS: This was a prospective, multicenter 2:1 randomized controlled trial of EBVs plus standard of care or standard of care alone (SoC). Primary outcome at 3 months post-procedure was the percentage of subjects with FEV1 improvement from baseline of 12% or greater. Changes in FEV1, residual volume, 6-minute-walk distance, St. George's Respiratory Questionnaire score, and modified Medical Research Council score were assessed at 3 and 6 months, and target lobe volume reduction on chest computed tomography at 3 months. MEASUREMENTS AND MAIN RESULTS: Ninety seven subjects were randomized to EBV (n = 65) or SoC (n = 32). At 3 months, 55.4% of EBV and 6.5% of SoC subjects had an FEV1 improvement of 12% or more (P < 0.001). Improvements were maintained at 6 months: EBV 56.3% versus SoC 3.2% (P < 0.001), with a mean ± SD change in FEV1 at 6 months of 20.7 ± 29.6% and -8.6 ± 13.0%, respectively. A total of 89.8% of EBV subjects had target lobe volume reduction greater than or equal to 350 ml, mean 1.09 ± 0.62 L (P < 0.001). Between-group differences for changes at 6 months were statistically and clinically significant: ΔEBV-SoC for residual volume, -700 ml; 6-minute-walk distance, +78.7 m; St. George's Respiratory Questionnaire score, -6.5 points; modified Medical Research Council dyspnea score, -0.6 points; and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, -1.8 points (all P < 0.05). Pneumothorax was the most common adverse event, occurring in 19 of 65 (29.2%) of EBV subjects. CONCLUSIONS: EBV treatment in hyperinflated patients with heterogeneous emphysema without collateral ventilation resulted in clinically meaningful benefits in lung function, dyspnea, exercise tolerance, and quality of life, with an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT02022683).

Endothelial glycocalyx layer shedding following lung resection.

AIM: We investigated if the serum biomarkers of endothelial glycocalyx layer (EGL) disruption, heparan sulfate proteoglycan (HSPG) and syndecan-1 (SDC1) were elevated following lung resection surgery. METHODS: Plasma samples were collected from 16 patients undergoing lobectomy for primary lung cancer. HSPG and SDC1 were measured at five perioperative timepoints. Postoperative oxygenation was recorded. RESULTS: Post-hoc pair wise comparisons showed SDC1 concentration was significantly elevated on postoperative day 2, p < 0.001. There was no relationship found between HSPG or SDC1 levels and postoperative oxygenation. CONCLUSION: Our pilot study is the first to provide evidence of EGL disruption following lung resection surgery. We hypothesize that EGL disruption is involved in the pathogenesis of post-lung resection acute lung injury. Abstract presentation: This work was presented in a part at the Anaesthetic Research Society Spring Meeting, Royal College of Anaesthetists, London, UK, 22 April 2015.