Joint ERS/EACTS/ESTS clinical practice guidelines on adults with spontaneous pneumothorax.

OBJECTIVES: The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP. METHODS: This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading, Recommendation, Assessment, Development and Evaluation). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations. RESULTS: The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis. CONCLUSIONS: With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made. SHAREABLE ABSTRACT: This update of an ERS Task Force statement from 2015 provides a concise comprehensive update of the literature base. 24 evidence-based recommendations were made for management of pneumothorax, balancing clinical priorities and patient views.https://bit.ly/3TKGp9e.

Joint ERS/EACTS/ESTS clinical practice guidelines on adults with spontaneous pneumothorax.

BACKGROUND: The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP. METHODS: This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading of Recommendations, Assessment, Development and Evaluations). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations. RESULTS: The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis. CONCLUSIONS: With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made.

Sympathicotomy for isolated facial blushing: long-term follow-up of a randomized trial.

OBJECTIVES: Thoracoscopic sympathicotomy may be an effective treatment for disabling facial blushing in selected patients. Short- and mid-term results are good but very long-term results are scarce in the medical literature and there is no knowledge which extent of sympathicotomy is better long-term for isolated facial blushing. METHODS: We previously randomized 100 patients between a rib-oriented R2 or R2-R3 sympathicotomy for isolated facial blushing, and reported local effects, side effects and quality of life after 12 months. In the present study, we sent identical questionnaires to all patients after a median of 16 years (interquartile range 15-17 years). RESULTS: The response rate was 66%. Overall, 82% reported excellent or satisfactory results on facial blushing, with significant better local effect after R2 sympathicotomy compared with R2-R3 sympathicotomy. Patients who underwent R2 sympathicotomy were also significantly more satisfied with the operation. We found no significant difference between R2 and R2-R3 sympathicotomy in quality of life or rates of compensatory sweating (77%) and recurrence of blushing (41%) which was milder than preoperatively in most patients. CONCLUSIONS: R2 sympathicotomy should be the preferred approach for isolated facial blushing because of better local effect and higher satisfaction rates. Although this was a very long-term follow-up of the only randomized trial of its kind the response rate was limited leaving a risk of undetected bias.

Identification of Highly Sensitive Pleural Effusion Protein Biomarkers for Malignant Pleural Mesothelioma by Affinity-Based Quantitative Proteomics.

Malignant pleural mesothelioma (MPM) is an asbestos-associated, highly aggressive cancer characterized by late-stage diagnosis and poor prognosis. Gold standards for diagnosis are pleural biopsy and cytology of pleural effusion (PE), both of which are limited by low sensitivity and markedly inter-observer variations. Therefore, the assessment of PE biomarkers is considered a viable and objective diagnostic tool for MPM diagnosis. We applied a novel affinity-enrichment mass spectrometry-based proteomics method for explorative analysis of pleural effusions from a prospective cohort of 84 patients referred for thoracoscopy due to clinical suspicion of MPM. Protein biomarkers with a high capability to discriminate MPM from non-MPM patients were identified, and a Random Forest algorithm was applied for building classification models. Immunohistology of pleural biopsies confirmed MPM in 40 patients and ruled out MPM in 44 patients. Proteomic analysis of pleural effusions identified panels of proteins with excellent diagnostic properties (90-100% sensitivities, 89-98% specificities, and AUC 0.97-0.99) depending on the specific protein combination. Diagnostic proteins associated with cancer growth included galactin-3 binding protein, testican-2, haptoglobin, Beta ig-h3, and protein AMBP. Moreover, we also confirmed previously reported diagnostic accuracies of the MPM markers fibulin-3 and mesothelin measured by two complementary mass spectrometry-based methods. In conclusion, a novel affinity-enrichment mass spectrometry-based proteomics identified panels of proteins in pleural effusion with extraordinary diagnostic accuracies, which are described here for the first time as biomarkers for MPM.

Procedural Aspects of Epidural Catheter Placement: A Prospective Observational Study of 173 Epidural Catheter Insertions.

OBJECTIVE: The risks and benefits of epidural analgesia have been studied extensively, but information regarding many other aspects of epidural catheter insertion is limited. The authors aimed to add information regarding procedural pain, procedure duration, failure rates, and the effect of experience to the ongoing discussion on this procedure. DESIGN: A prospective observational study. SETTING: A Danish tertiary hospital. PARTICIPANTS: Patients scheduled to undergo video-assisted thoracic surgery. INTERVENTIONS: Epidural catheter insertion in 173 patients undergoing video-assisted thoracic surgery for lung cancer. MEASUREMENTS AND MAIN RESULTS: The authors recorded the time required for the epidural insertion procedure, the attempts used, insertion level, access use, patient position, placement technique used, and the designation of the physician placing the catheter. Furthermore, the authors asked the patients to evaluate the expected procedural pain, and after the procedure the authors asked them to evaluate the actual level of pain experienced. Six and 24 months after discharge, the authors examined persistent sequelae by using questionnaire assessments. The median procedure duration was 13 minutes, with 75% of the catheters placed within 22 minutes. Actual procedure-related pain (mean score [M] = 3.5, SD = 2.0) was significantly (p < 0.0001) less than that expected before the procedure (M = 4.9, SD = 2.0). The patients' expected pain, attempts required for successful catheter placement, and approach used to access the epidural space significantly affected the actual procedure-related pain (p = 0.001, p ≤ 0.003, and p = 0.023, respectively). Persistent pain and sensory disturbances were observed in 11% and 4% of the patients, respectively, after 6 months and in 6% and 4% of the patients, respectively, after 2 years. CONCLUSIONS: In this study, the authors examined several lesser-known aspects of epidural procedures. The use of epidural analgesia as part of the pain management plan after surgery requires a more complex evaluation instead of merely discussing the possibility of procedural infections, hematomas, or neurologic injuries. The procedure time, patients' expected and experienced pain related to the procedure, and the potential long-term side effects should be a part of the decision-making process.

Intrapleural fibrinolysis and DNase versus video-assisted thoracic surgery (VATS) for the treatment of pleural empyema (FIVERVATS): protocol for a randomised, controlled trial - surgery as first-line treatment.

INTRODUCTION: Pleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS)-guided pigtail drainage. Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of video-assisted thoracoscopic surgery (VATS) as first-line treatment. The aim of this study is to determine the difference in outcome in patients diagnosed with complex parapneumonic effusion (stage II) and pleural empyema (stage III) who are treated with either VATS surgery or TUS-guided drainage and intrapleural therapy (fibrinolytic (Alteplase) with DNase (Pulmozyme)) as first-line treatment. METHODS AND ANALYSIS: A national, multicentre randomised, controlled study. Totally, 184 patients with a newly diagnosed community acquired complicated parapneumonic effusion or pleural empyema are randomised to either (1) VATS procedure with drainage or (2) TUS-guided pigtail catheter placement and intrapleural therapy with Actilyse and DNase. The total follow-up period is 12 months. The primary endpoint is length of hospital stay and secondary endpoints include for example, mortality, need for additional interventions, consumption of analgesia and quality of life. ETHICS AND DISSEMINATION: All patients provide informed consent before randomisation. The research project is carried out in accordance with the Helsinki II Declaration, European regulations and Good Clinical Practice Guidelines. The Scientific Ethics Committees for Denmark and the Danish Data Protection Agency have provided permission. Information about the subjects is protected under the Personal Data Processing Act and the Health Act. The trial is registered at www. CLINICALTRIALS: gov, and monitored by the regional Good clinical practice monitoring unit. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences. TRIAL REGISTRATION NUMBER: NCT04095676.

New Chest Drainage Unit with Integrated CO2-Detector Demonstrates False Air Leak.

BACKGROUND: Postoperative observed air leakage does not always originate from parenchymal defects but may arise from defects in the chest drainage unit, connections or reverse airflow in water seals. We investigated such false air leakage using a new chest drainage unit with a built-in CO2-detector and an electronic chest drainage unit. METHODS: Two types of chest drainage units were tested in a simple porcine model: A well-known electronic chest drainage unit and a new chest drainage unit with integrated CO2-detector. We created a setup of true air leakage-a parenchymal lesion, and false air leakage-allowing air to flow into the thoracic cavity alongside the chest drain. RESULTS: We demonstrated that the new chest drainage unit with a built-in CO2-detector can distinguish between experimentally induced true air leakage and false air leakage. CONCLUSION: Available chest drainage systems do not allow direct assessment of true or false air leakage, which may increase chest drain duration unnecessarily. The integration of a CO2-sensitive color indicator into a chest drainage unit allows simple distinction between false air leak and true air leak, which may improve postoperative management.

A Diaphragmic Traction Suture Increases Pleural Cavity Volume and Surgical Field Overview During Video-Assisted Thoracoscopic Surgery.

OBJECTIVES: An elevated hemidiaphragm may impair surgical field overview during video assisted thoracoscopic surgery (VATS) and may consequently jeopardize a safe surgical procedure or prolong the duration of surgery. The aim of this study was to evaluate if tension applied to a diaphragmatic suture improves the surgical field overview. METHODS: Following informed consent and at the surgeon's discretion during elective VATS procedures, a single stitch was placed at the posterior tendinous border of the diaphragm and retracted through the camera port. The surgical field overview was evaluated using a numeric rating scale (1-10) by the surgeon before and after applying tension during the procedure, and later by 9 VATS surgeons (> 10 years' experience) using video recordings. RESULTS: During a 4-month period, 43 patients scheduled for elective VATS by two surgeons gave informed consent to participate. The hemidiaphragm was elevated to such an extent in 27 patients that the surgeon placed a diaphragmatic stitch suture. When tension was applied to the suture, surgical field overview improved significantly (p < 0.001). CONCLUSION: A diaphragmatic traction suture improves surgical field overview in selected patients with elevation of the hemidiaphragm. This simple procedure may facilitate VATS in patients with impaired surgical field overview and consequently improve safety during VATS. CLINICAL TRIAL NUMBER: http://ClinicalTrials.gov (No. NCT04837950).

A Newly Developed Chest Drainage Unit with an Integrated CO2 Detector.

PURPOSE: Postoperative air leakage does not always originate from parenchymal defects. In some cases, it may arise from defects in the chest drainage unit itself or connections, or from reverse airflow in water seals. The aim of the present study was to test a new chest drainage unit in the clinic, where an integrated CO2-sensitive colour indicator helps to distinguish false air leakage from true air leakage. METHODS: Over a 3-week period, 14 consecutive patients were operated upon using either an open approach (for bilobectomies) or VATS (for diagnostic procedures or lobectomies). All patients received general anaesthesia with double-lumen intubation. All patients had a 24-Fr chest tube connected to a chest drainage unit with a built-in CO2-detector. RESULTS: In all patients with air leakage after surgery, we found a colour change in the CO2-sensitive colour indicator, confirming "true air leakage". One patient had prolonged air leakage. None of the patients had pneumothorax after removal of the chest tube and no patients had wound infections or any other complications. CONCLUSION: The chest drainage unit described here was easily implemented in the clinic and clearly confirmed true air leakage in all patients with air leakage after lung surgery. It allowed safe and appropriate timing for chest tube removal with no need for reinsertion in a broad cohort of patients referred for thoracic surgery.

Evaluation of a Powered Vascular Stapler in Video-Assisted Thoracic Surgery Lobectomy.

BACKGROUND: A narrow-profile powered vascular stapler (PVS) was developed to provide superior access and precise staple placement in thoracic procedures. The objective of this study was to determine if the PVS would yield an equivalent rate of hemostatic interventions compared with standard of care (SOC) staplers in video-assisted thoracoscopic surgery lobectomy. MATERIALS AND METHODS: A randomized, controlled, multicenter study was conducted comparing PVS with SOC staplers in lobectomies performed for non-small cell lung cancer. The primary performance endpoint was the incidence of intraoperative hemostatic interventions, and the primary safety endpoint was the frequency of postoperative bleeding-related interventions. RESULTS: A total of 98 subjects participated in the SOC group and 103 in the PVS group. Rates of intraoperative hemostatic interventions were 5.3% and 8.3% for the SOC and PVS groups, respectively. These rates were not statistically different (P = 0.137), although the upper bound of the 95% confidence interval for the difference in intervention rates between PVC and SOC exceeded a predefined 3% criterion for equivalence. Simple compressions were performed more frequently in the PVS subjects, which accounted for the higher intervention rate in this group. Postoperative interventions for bleeding were required in one SOC subject (1.0%) and one subject from the PVS group (0.9%). Procedure-related adverse events occurred in 21 (21.9%) SOC subjects and 23 (21.9%) PVS subjects, with no adverse events related to use of the study devices. CONCLUSIONS: The PVS exhibited similar overall safety and effectiveness to SOC staplers in video-assisted thoracoscopic surgery lobectomy.

Platelet function in lung cancer patients undergoing lobectomy.

A growing interest concerns arterial thromboembolic disease in cancer patients. As platelets may be key players in this process, investigation of platelet aggregation in cancer patients is of importance. We aimed to investigate platelet aggregation in patients with lung cancer prior to surgery and during video-assisted thoracoscopic surgery (VATS) lobectomy compared with lobectomy performed through a thoracotomy. We included 93 patients (VATS + low molecular weight heparin (LMWH), n = 32; VATS no LMWH, n = 31; thoracotomy + LMWH, n = 30). Data obtained from 121 healthy individuals were used for comparison prior to surgery. Platelet aggregation was analysed by impedance aggregometry using adenosine diphosphate 6.5 µM (ADPtest) and collagen 3.2 µg/mL (COLtest) as agonists. Prior to surgery, platelet aggregation was significantly increased in both VATS-patients (ADPtest, p < .0001; COLtest, p = .0002) and patients undergoing thoracotomy (ADPtest, p < .0001; COLtest, p < .0001) compared with healthy individuals. Platelet aggregation did not differ between VATS-patients and thoracotomy patients prior to surgery (p-values >.11). At the first postoperative day, VATS-patients demonstrated significantly higher collagen-induced platelet aggregation than preoperatively (p = .001), but the increase in platelet aggregation did not differ significantly between VATS and thoracotomy patients (p-values ≥.24). At the second postoperative day, platelet aggregation was significantly reduced in thoracotomy patients compared with the preoperative level (ADPtest, p = .002; COLtest, p = .05). In conclusion, platelet aggregation was significantly increased in patients with primary lung cancer prior to surgery compared with healthy individuals. At the first postoperative day, platelet aggregation was significantly higher than the preoperative level in VATS-patients; however, this increase did not differ between patient groups.

Incidence of primary spontaneous pneumothorax: a validated, register-based nationwide study.

OBJECTIVES: The incidence of primary spontaneous pneumothorax is partly unknown. Commonly quoted estimates were published decades ago and recent large-scale epidemiological publications lack validation. We validated the pneumothorax diagnosis in a national registry and estimated the incidence of primary spontaneous pneumothorax in young patients. METHODS: Complete data on patients with an assigned pneumothorax diagnosis was retrieved from the National Danish Patient Registry. Initially, we validated the diagnosis in a selected population: all patient charts with an assigned pneumothorax diagnosis from one cardiothoracic department over a 25-year period (1984-2008) were reviewed. Subsequently, the national incidence of primary spontaneous pneumothorax in young, healthy individuals was estimated by restricting our population to patients ≤40 years of age admitted during a 5-year period (2009-2014). We performed a systematic read-though of patient charts in 50% of the complete national cohort to ensure that we only included patients with their first episode of primary spontaneous pneumothorax. RESULTS: Validation revealed a poor inter-rater agreement (κ=0.08). Therefore, we abstained from further analysis on directly retrieved data from the national database. Subsequently, a systematic re-evaluation of 7022 patients revealed an incidence rate of 12.3 cases per 100 000 (95% CI 11.5-13.1) in males and 2.2 cases per 100 000 (95% CI 1.9-2.6) in females (male/female ratio 5.9). Compared with the general Danish population, pneumothorax patients had a lower body mass index (p<0.001) and smoked more than the Danish population in general (p<0.001). CONCLUSIONS: The incidence of primary spontaneous pneumothorax in a validated national study was lower than previously reported.

Cost-utility analysis of minimally invasive surgery for lung cancer: a randomized controlled trial.

OBJECTIVES: Minimally invasive video-assisted thoracic surgery (VATS) was first introduced in the early 1990s. For decades, numerous non-randomized studies demonstrated advantages of VATS over thoracotomy with lower morbidity and shorter hospital stay, but only recently did a randomized trial document that VATS results in lower pain scores and better quality of life. Opposing arguments for VATS have always been increased costs and concerns about oncological adequacy. In this paper, we aim to investigate the cost-effectiveness of VATS. METHODS: The study was designed as a cost-utility analysis of the first 12 months following surgery and was performed together with a clinical randomized controlled trial of VATS versus thoracotomy for lobectomy of stage 1 lung cancer during a 6-year period (2008-2014). All health-related expenses were retrieved from a national database (Statistics Denmark) including hospital readmissions, outpatient clinic visits, prescription medication costs, consultations with general practitioners, specialists, physiotherapists, psychologists and chiropractors. RESULTS: One hundred and three VATS patients and 103 thoracotomy patients were randomized. Mean costs per patient operated by VATS were 103 108 Danish Kroner (Dkr) (€13 818) and 134 945 Dkr (€18 085) by thoracotomy, making the costs for VATS 31 837 Dkr (€4267) lower than thoracotomy (P < 0.001). The difference in quality-adjusted life years gained over 52 weeks of follow-up was 0.021 (P = 0.048, 95% confidence interval -0.04 to -0.00015) in favour of VATS. The median duration of the surgical procedure was shorter after thoracotomy (79 vs 100 min; P < 0.001). The mean length of hospitalization was shorter following VATS (4.8 vs 6.7 days; P = 0.027). The use of other resources was not significantly different between groups. The costs of resources were lower in the VATS group. This difference was primarily due to reduced costs of readmissions (VATS 29 247 Dkr vs thoracotomy 51 734 Dkr; P < 0.001) and costs of outpatient visits (VATS 51 412 Dkr vs thoracotomy 61 575 Dkr; P = 0.012). CONCLUSIONS: VATS is a cost-effective alternative to thoracotomy following lobectomy for stage 1 lung cancer. Economical outcomes as measured by quality-adjusted life years were significantly better and overall costs were lower for VATS. CLINICAL TRIAL REGISTRATION NUMBER: NCT01278888.

The Influence of Suction on Chest Drain Duration After Lobectomy Using Electronic Chest Drainage.

BACKGROUND: Management of chest drains after thoracic surgery remains an area with little consensus. To optimize chest drainage algorithms with electronic chest drainage systems, a randomized controlled trial comparing low variable suction (-5 cm H2O) versus high variable suction (-20 cm H2O) was conducted. METHODS: This was a prospective open label randomized trial in patients undergoing lobectomy. Sample size was calculated from a clinical relevant difference in chest drain duration as 1 full day. End points were chest drain duration and length of hospitalization. Data were analyzed by Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression. RESULTS: The study randomized 106 patients. There was no statistical significant difference in chest drain duration and length of stay between the low-suction and the high-suction groups: Median chest drain duration and hospitalization were 25 hours (interquartile range [IQR] 21 to 55 hours) versus 28 hours (IQR 23 to 77 hours; p = 0.97) and 5 days (IQR 3 to 6 days) versus 5 days (IQR 3 to 7 days; p = 0.75), respectively. Multivariate analysis demonstrated that the diffusing capacity of the lung for carbon monoxide was the only significant predictor of chest drain duration (p = 0.015) and length of hospitalization (p = 0.003). Complications requiring reinsertion of the chest drain were significantly more frequent in the low-suction group (p = 0.03). CONCLUSIONS: There was no clinically relevant difference in chest drain duration or length of hospitalization, but reinsertions of chest drains were significantly more frequent in the low-suction group, a finding suggesting that low suction levels should not be used after lobectomy. Trial registry number is ISRCTN10408356.