The ESTS-AIR database-initial results of a multi-institutional database on airway surgery.

OBJECTIVES: Compared to lung resections, airway procedures are relatively rare in thoracic surgery. Despite this, a growing number of dedicated airway centres have formed throughout Europe. These centres are characterized by a close interdisciplinary collaboration and they often act as supra-regional referring centres. To date, most evidence of airway surgery comes from retrospective, single-centre analysis as there is a lack of large-scale, multi-institutional databases. METHODS: In 2018, an initiative was formed, which aimed to create an airway database within the framework of the ESTS database (ESTS-AIR). Five dedicated airway centres were asked to test the database in a pilot phase. A 1st descriptive analysis of ESTS-AIR was performed. RESULTS: A total of 415 cases were included in the analysis. For adults, the most common indication for airway surgery was post-tracheostomy stenosis and idiopathic subglottic stenosis; in children, most resections/reconstructions had to be performed for post-intubation stenosis. Malignant indications required significantly longer resections [36.0 (21.4-50.6) mm] when compared to benign indications [26.6 (9.4-43.8) mm]. Length of hospital stay was 11.0 (4.1-17.3) days (adults) and 13.4 (7.6-19.6) days (children). Overall, the rates of complications were low with wound infections being reported as the most common morbidity. CONCLUSIONS: This evaluation of the 1st cases in the ESTS-AIR database allowed a large-scale analysis of the practice of airway surgery in dedicated European airway centres. It provides proof for the functionality of ESTS-AIR and sets the basis for rolling out the AIR subsection to all centres participating in the ESTS database.

Intrinsic pulmonary sealing, its mechanisms and impact on validity and translational value of lung sealant studies: a pooled analysis of animal studies.

Background: No validated and standardized animal models of pulmonary air leakage (PAL) exist for testing aerostatic efficacy of lung sealants. Lack of negative control groups in published studies and intrinsic sealing mechanisms of healthy animal lungs might contribute to a translational gap, leading to poor clinical results. This study aims to address the impact of intrinsic sealing mechanisms on the validity of PAL models, and investigate the conditions required for an ovine model of PAL for lung sealant testing. Methods: An ovine acute aerostasis model was developed, consisting of a bilateral thoracotomy with lesion creation, chest tube insertion and monitoring of air leaks using digital drains (≥80 minutes), under spontaneous respiration. Healthy mixed-breed adult female sheep were used and all in vivo procedures were performed under terminal anesthesia. Superficial parenchymal lesions were tested post-mortem and in vivo, extended lesions including bronchioles (deep bowl-shaped and sequential lung amputation lesions) were tested in vivo. Experiment outcomes include air leakage (AL), minimal leaking pressure (MLP) and histology. Results: Two post-mortem (N=4 superficial parenchymal lesions) and 10 in vivo experiments (N=5 superficial parenchymal and N=16 lesions involving bronchioles) were performed. In contrast to the post-mortem model, superficial parenchymal lesions in vivo showed less air leak [mean flow ± standard deviation (SD): 760±693 vs. 42±33 mL/min, P=0.055]. All superficial parenchymal lesions in vivo sealed intrinsically within a median time of 20 minutes [interquartile range (IQR), 10-75 minutes]. Histology of the intrinsic sealing layer revealed an extended area of alveolar collapse below the incision with intra-alveolar hemorrhage. Compared to superficial parenchymal lesions in vivo, lesions involving bronchioles induced significantly higher air leak post-operatively (normalized mean flow ± SD: 459±221 mL/min, P=0.003). At termination, 5/9 (55.6%) were still leaking (median drain time: 273 minutes, IQR, 207-435 minutes), and intrinsic sealing for the remaining lungs occurred within a median of 115 minutes (IQR, 52-245 minutes). Conclusions: Lung parenchyma of healthy sheep shows a strong intrinsic sealing mechanism, explained pathologically by an extended area of alveolar collapse, which may contribute to a translational gap in lung sealant research. A meaningful ovine model has to consist of deep lesions involving bronchioles of >⌀1.5 mm. Further research is needed to develop a standardized PAL model, to improve clinical effectiveness of lung sealants.

Surviving the nonsurvivable combination of a mycotic aneurysm progressing into a concomitant aorto-bronchial- and aorto-esophageal fistula, a case report.

BACKGROUND: Aortic mycotic aneurysms are a rare but life-threatening condition and may be associated with aorto-bronchial- and aorto-esophageal fistulas. Although both very rare, they carry a high mortality and require (urgent) surgical intervention. Surviving all three conditions concomitantly is extraordinary. We describe a patient who underwent staged repair of such combined defects.

Sealing effectiveness of a novel NHS-POx based patch: experiments in a dynamic ex vivo porcine lung.

Background: Sealants are used to prevent prolonged pulmonary air leakage (PAL) after lung resections (incidence 5.6-30%). However, clinical evidence to support sealant use is insufficient, with an unmet need for a more effective product. We compared a novel gelatin patch impregnated with functionalized polyoxazolines (NHS-POx) (GATT-Patch) to commercially available sealant products. Methods: GATT-Patch Single/Double layers were compared to Progel®, Coseal®, Hemopatch® and TachoSil® in an ex vivo porcine lung model (first experiment). Based on these results, a second head-to-head comparison between GATT-Patch Single and Hemopatch® was performed. Air leakage (AL) was assessed in three settings using increasing ventilatory pressures (max =70 cmH2O): (I) baseline, (II) with 25 mm × 25 mm superficial pleural defect, and (III) after sealant application. Lungs floating on saline (37 ℃) were video recorded for visual AL assessment. Pressure and tidal volumes were collected from the ventilator, and bursting pressure (BP), AL and AL-reduction were determined. Results: Per sealant 10 measurements were performed (both experiments). In the first experiment, BP was superior for GATT-Patch Double (60±24 cmH2O) compared to TachoSil® (30±11 cmH2O, P<0.001), Hemopatch® (33±6 cmH2O, P=0.006), Coseal® (25±13 cmH2O, P=0.001) and Progel® (33±11 cmH2O, P=0.005). AL-reduction was superior for GATT-Patch Double (100%±1%) compared to Hemopatch® (46%±50%, P=0.010) and TachoSil® (31%±29%, P<0.001), and also for GATT-Patch Single (100%±14%, P=0.004) and Progel (89%±40%, P=0.027) compared to TachoSil®. In the second experiment, GATT-Patch Single was superior regarding BP (45±10 vs. 40±6 cmH2O, P=0.043) and AL-reduction (100%±11% vs. 68%±40%, P=0.043) when compared to Hemopatch®. Conclusions: The novel NHS-POx patch shows promise as a lung sealant, demonstrating elevated BP, good adhesive strength and a superior AL-reduction.

Variations in current clinical practice of postoperative pericardial effusion: a questionnaire study.

OBJECTIVE: Postoperative pericardial effusion (PPE) occurs frequently after cardiac surgery, potentially leading to life-threatening cardiac tamponade. Specific treatment guidelines are currently lacking, possibly leading to variations in clinical practice. Our goal was to assess clinical PPE management and evaluate variation between centres and clinicians. METHODS: A nationwide survey was sent to all interventional cardiologists and cardiothoracic surgeons in the Netherlands, regarding their preferred diagnostic and treatment modality of PPE. Clinical preferences were explored utilising four patient scenarios, each with a high/low echocardiographic and clinical suspicion of cardiac tamponade. Scenarios were also stratified by three PPE sizes (<1 cm, 1-2 cm, >2 cm). RESULTS: In total, 46/140 interventional cardiologists and 48/120 cardiothoracic surgeons responded (27/31 contacted centres). Cardiologists favoured routine postoperative echocardiography in all patients (44%), whereas cardiothoracic surgeons preferred routine imaging after specific procedures, especially mitral (85%) and tricuspid (79%) valve surgery. Overall, pericardiocentesis (83%) was preferred over surgical evacuation (17%). Regarding all patient scenarios, cardiothoracic surgeons significantly preferred evacuation compared with cardiologists (51% vs 37%, p<0.001). This was also observed with cardiologists employed in surgical centres compared with non-surgical centres (43% vs 31%, p=0.02). Inter-rater analysis varied from poor to near-excellent (к 0.22-0.67), suggesting varying PPE treatment preferences within one centre. CONCLUSION: There is significant variation in the preferred management of PPE between hospitals and clinicians, even within the same centre, possibly due to the lack of specific guidelines. Therefore, robust results of a systematic approach to PPE diagnosis and treatment are needed to formulate evidence-based recommendations and optimise patient outcome.

Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer: A Randomized Clinical Trial.

PURPOSE: Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking. METHODS: Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior < .0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality. RESULTS: Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior = .0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior = .0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first (P = .4940). CONCLUSION: On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.

Evaluating and developing sealants for the prevention of pulmonary air leakage: A systematic review of animal models.

Sealants may provide a solution for pulmonary air leakage (PAL), but their clinical application is debatable. For sealant comparison, standardized animal models are lacking. This systematic review aims to assess methodology and quality of animal models for PAL and sealant evaluation. All animal models investigating lung sealing devices (e.g., staplers, glues, energy devices) to prevent or treat PAL were retrieved systematically from Embase, Pubmed and Web of science. Methodological study characteristics, risk of bias, reporting quality and publication bias were assessed. A total of 71 studies were included (N = 75 experiments, N = 1659 animals). Six different species and 18 strains were described; 92% of experiments used healthy animals, disease models were used in only six studies. Lesions to produce PAL were heterogenous, and only 11 studies used a previously reported technique, encompassing N = 5 unique lesions. Clinically relevant outcomes were used in the minority of studies (imaging 16%, air leak 10.7%, air leak duration 4%). Reporting quality was poor, but revealed an upward trend per decade. Overall, high risk of bias was present, and only 18.7% used a negative control group. All but one study without control groups claimed positive outcomes (95.8%), in contrast to 84.3% using positive or negative control groups, which also concluded equivocal, adverse or inconclusive outcomes. In conclusion, animal studies evaluating sealants for prevention of PAL are heterogenous and of poor reporting quality. Using negative control groups, disease models and quantifiable outcomes seem important to increase validity and relevance. Further research is needed to reach consensus for model development and standardization.

Ex-vivo exploration of an endobronchial sentinel lymph node procedure in lung cancer for optimizing workflow and evaluating feasibility of novel imaging tools.

Background: Early-stage lung cancer is treated with curative intent by surgery or radiotherapy. However, upstaging is frequently seen after surgery in clinical N0 lung cancer patients, and despite curative intent, 2-year recurrence rates of 9-28% are reported. A sentinel lymph node (SLN) procedure could improve the staging accuracy. We explored the feasibility of performing a navigation bronchoscopy based SLN procedure in human ex-vivo lung cancer specimens to optimize procedural parameters and assess a novel injection tool. Methods: Ten lung resection specimens were included and allocated to either peri- or intratumoral injection of a tracer combining 99mTc-nanocolloid and indocyanine green (ICG) while varying the injection volume. A Pioneer Plus catheter with a pre-angulated 24G needle and an ultrasound (US)-element was used to perform real-time US guided transbronchial injections at multiple locations. Thereafter, single photon emission computed tomography/computed tomography (SPECT/CT)-scanning was performed to image injection depots and to assess their location relative to the tumor. Results: An average volume of 0.7 mL (range, 0.3-1.2 mL) with an average activity of 89.5 MBq 99mTc (range, 35.4-188.0 MBq) was injected. Intratumoral injections in non-solid and solid tumors were successful in 100% and 64.3% respectively, while 100% of peritumoral injections in solid tumors were successful. The US-element of the catheter allowed real-time imaging and was able to visualize all tumors and 67.4% of all injections. SPECT/CT-scanning visualized 76.7% of the injection depots. Conclusions: A navigation bronchoscopy mediated SLN procedure seems technically feasible. The Pioneer Plus is a suitable catheter to place tracer depots at multiple intra-/peri-tumoral sites, while receiving real-time feedback on the needle localization in relation to the tumor. The next step of in-vivo injections will determine if tracer drainage to the SLN can also be detected on pre- and per-operative imaging.

Acute pain management after thoracoscopic lung resection: a systematic review and explorative meta-analysis.

OBJECTIVES: Pain after thoracoscopic surgery may increase the incidence of postoperative complications and impair recovery. Guidelines lack consensus regarding postoperative analgesia. We performed a systematic review and meta-analysis to determine the mean pain scores of different analgesic techniques (thoracic epidural analgesia, continuous or single-shot unilateral regional analgesia and only systemic analgesia) after thoracoscopic anatomical lung resection. METHODS: Medline, Embase and Cochrane databases were searched until 1 October 2022. Patients undergoing at least >70% anatomical resections through thoracoscopy reporting postoperative pain scores were included. Due to a high inter-study variability an explorative meta-analysis next to an analytic meta-analysis was performed. The quality of evidence has been evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: A total of 51 studies comprising 5573 patients were included. Mean 24, 48 and 72 h pain scores with 95% confidence interval on a 0-10 scale were calculated. Length of hospital stay, postoperative nausea and vomiting, additional opioids and the use of rescue analgesia were analysed as secondary outcomes. A common-effect size was estimated with an extreme high heterogeneity for which pooling of the studies was not appropriate. An exploratory meta-analysis demonstrated acceptable mean pain scores of Numeric Rating Scale <4 for all analgesic techniques. CONCLUSIONS: This extensive literature review and attempt to pool mean pain scores for meta-analysis demonstrates that unilateral regional analgesia is gaining popularity over thoracic epidural analgesia in thoracoscopic anatomical lung resection, despite great heterogeneity and limitations of current studies precluding such recommendations. PROSPERO REGISTRATION: ID number 205311.

Decision Making during the Learning Curve of Minimally Invasive Mitral Valve Surgery: A Focused Review for the Starting Minimally Invasive Surgeon.

Minimally invasive mitral valve surgery is evolving rapidly since the early 1990's and is now increasingly adopted as the standard approach for mitral valve surgery. It has a long and challenging learning curve and there are many considerations regarding technique, planning and patient selection when starting a minimally invasive program. In the current review, we provide an overview of all considerations and the decision-making process during the learning curve.

Long-term follow-up of voice changes after cervical mediastinoscopy.

BACKGROUND: Vocal cord palsy after cervical mediastinoscopy is usually reported at less than 1%. However, its incidence might be underestimated and no follow-up studies are available. Our study aimed to evaluate the incidence of voice changes after cervical mediastinoscopy and report on long-term outcomes, including quality of life, after at least one-year follow-up. METHODS: A retrospective cohort study was performed, considering all patients who underwent cervical mediastinoscopy in our center between January 2011 and April 2016. Patients with pre-existing voice changes, voice changes only after pulmonary resection and patients who underwent neoadjuvant chemo(radio)therapy were excluded. Voice changes with full recovery within 14 days were attributed to intubation-related causes. Follow-up questionnaires, including the standardized Voice Handicap Index, were sent to patients with documented voice changes. RESULTS: Of 270 patients who were included for final analysis, 17 (6.3%) experienced voice changes after cervical mediastinoscopy, which persisted > 2 years in 4 patients (1.5%), causing mild to moderate disabilities in daily living. Twelve patients (out of 17, 71%) were referred for otolaryngology consultation, and paresis of the left vocal cord suggesting recurrent laryngeal nerve injury was confirmed in 10 (3.7% of our total study group). Additionally, 83% of the patients who were referred for otolaryngology consultation received voice treatment. Recovery rate after vocal exercises therapy and injection laryngoplasty was respectively 71% and 33%. CONCLUSIONS: Voice changes after cervical mediastinoscopy is an underreported complication, with an incidence of at least 6.3% in our retrospective study, with persisting complaints in at least 1.5% of patients, leading to mild to moderate disabilities in daily living. These findings highlight the need for appropriate patient education for this underestimated complication, as well as the exploration of possible preventive measures.

Timing of cardiac surgery during pregnancy: a patient-level meta-analysis.

AIMS: To investigate the association between the timing of cardiac surgery during pregnancy and both maternal and foetal outcomes. METHODS AND RESULTS: Studies published up to 6 February 2021 on maternal and/or foetal mortality after cardiac surgery during pregnancy that included individual patient data were identified. Maternal and foetal mortality was analysed per trimester for the total population and stratified for patients who underwent caesarean section (CS) prior to cardiac surgery (Caesarean section (CaeSe) group) vs. patients who did not (Cardiac surgery (CarSu) group). Multivariable logistic regression analysis was performed to evaluate predictors of both maternal and foetal mortality. In total, 179 studies were identified including 386 patients of which 120 underwent CS prior to cardiac surgery. Maternal mortality was 7.3% and did not differ significantly among trimesters of pregnancy (P = 0.292) nor between subgroup CaeSe and CarSu (P = 0.671). Overall foetal mortality was 26.5% and was lowest when cardiac surgery was performed during the third trimester (10.3%, P < 0.01). CS prior to surgery was significantly associated with a reduced risk of foetal mortality in a multivariable model [odds ratio 0.19, 95% confidence interval [0.06-0.56)]. Trimester was not identified as an independent predictor for foetal nor maternal mortality. CONCLUSION: Maternal mortality after cardiac surgery during pregnancy is not associated with the trimester of pregnancy. Cardiac surgery is associated with high foetal mortality but is significantly lower in women where CS is performed prior to cardiac surgery. When the foetus is viable, CS prior to cardiac surgery might be safe. When CS is not feasible, trimester stage does not seem to influence foetal mortality.

Isolation of multipotent progenitor cells from pleura and pericardium for tracheal tissue engineering purposes.

Tissue engineering (TE) of long tracheal segments is conceptually appealing for patients with inoperable tracheal pathology. In tracheal TE, stem cells isolated from bone marrow or adipose tissue have been employed, but the ideal cell source has yet to be determined. When considering the origin of stem cells, cells isolated from a source embryonically related to the trachea may be more similar. In this study, we investigated the feasibility of isolating progenitor cells from pleura and pericard as an alternative cells source for tracheal tissue engineering. Porcine progenitor cells were isolated from pleura, pericard, trachea and adipose tissue and expanded in culture. Isolated cells were characterized by PCR, RNA sequencing, differentiation assays and cell survival assays and were compared to trachea and adipose-derived progenitor cells. Progenitor-like cells were successfully isolated and expanded from pericard and pleura as indicated by gene expression and functional analyses. Gene expression analysis and RNA sequencing showed a stem cell signature indicating multipotency, albeit that subtle differences between different cell sources were visible. Functional analysis revealed that these cells were able to differentiate towards chondrogenic, osteogenic and adipogenic lineages. Isolation of progenitor cells from pericard and pleura with stem cell features is feasible. Although functional differences with adipose-derived stem cells were limited, based on their gene expression, pericard- and pleura-derived stem cells may represent a superior autologous cell source for cell seeding in tracheal tissue engineering.

Surgery without preoperative histological confirmation of lung cancer: what is the current clinical practice?

BACKGROUND: There are discordances in the guidelines regarding the need to acquire histological diagnosis before surgical treatment of (presumed) lung cancer. Preoperative histological confirmation is always encouraged in this setting to prevent unnecessary surgery or when sublobar resection for small-sized tumors is considered. The aim of this retrospective cohort study was to assess the proportion of patients undergoing lung cancer resection in the Netherlands without preoperative pathological confirmation, based on the intraoperative pathological diagnosis (IOD) rate, and to determine characteristics that may influence IOD frequency. METHODS: Data on 10,226 patients, who underwent surgical treatment for lung cancer from 2010 to 2015, were retrieved from the Netherlands National Cancer Registry. We registered an IOD when the date of diagnosis equaled the date of the first surgical intervention. Tabulations and multivariable logistic regression were used to identify predictive parameters for IOD. RESULTS: 36% of surgical procedures were classified as IOD, and decreased with increasing tumor size and extent of surgery (57% for segmentectomy, 39% for lobectomy and 11% for pneumonectomy). IOD was more frequently observed in adenocarcinoma (41%), varied between hospitals from 13% to 66% and was less common when patients were referred from a hospital where thoracic surgery was not performed. Previous history of cancer did not affect IOD. CONCLUSIONS: More than one-third of patients with suspected lung cancer in the Netherlands was operated without preoperative histological confirmation. There was significant variation in IOD rates between different hospitals, which deserves further detailed analysis when striving for uniform surgical quality of care for patients with lung cancer.

Variation in incidence, prevention and treatment of persistent air leak after lung cancer surgery.

OBJECTIVES: Persistent air leak (PAL; >5 days after surgery) is the most common complication after pulmonary resection and associated with prolonged hospital stay and increased morbidity. Literature is contradictory about the prevention and treatment of PAL. Variation is therefore hypothesized. The aim of this study is to understand the variation in the incidence, preventive management and treatment of PAL. METHODS: Data from the Dutch Lung Cancer Audit for Surgery were combined with results of an online survey among Dutch thoracic surgeons. The national incidence of PAL and case-mix corrected between-hospital variation were calculated in patients who underwent an oncological (bi)lobectomy or segmentectomy between January 2012 and December 2018. By multivariable logistic regression, factors associated with PAL were assessed. A survey was designed to assess variation in (preventive) management and analysed using descriptive statistics. Hospital-level associations between management strategies and PAL were assessed by univariable linear regression. RESULTS: Of 12 382 included patients, 9.0% had PAL, with a between-hospital range of 2.6-19.3%. Factors associated with PAL were male sex, poor lung function, low body mass index, high American Society of Anesthesiologists (ASA) score, pulmonary comorbidity, upper lobe resection, (bi)lobectomy (vs segmentectomy), right-sided tumour and robotic-assisted thoracic surgery. Perioperative (preventive) management of PAL differed widely between hospitals. When using water seal compared to suction drainage, the average incidence of PAL decreased 2.9%. CONCLUSIONS: In the Netherlands, incidence and perioperative (preventive) management of PAL vary widely. Using water seal instead of suction drainage and increasing awareness are potential measures to reduce this variation.

MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): a statistical analysis plan.

BACKGROUND: Invasive mediastinal nodal staging is recommended by guidelines in selected patients with resectable non-small cell lung cancer (NSCLC). Endosonography is recommended as initial staging technique, followed by confirmatory mediastinoscopy in case of negative N2 or N3 cytology after endosonography. Confirmatory mediastinoscopy however is under debate owing its limited additional diagnostic value, its associated morbidity and its delay in the start of lung cancer treatment. The MEDIASTrial examines whether confirmatory mediastinoscopy can be safely omitted after negative endosonography in mediastinal nodal staging of NSCLC. The present work is the proposed statistical analysis plan of the clinical consequences of omitting mediastinoscopy, which is submitted before closure of the MEDIASTrial and before knowledge of any results was done to enhance transparency of scientific behaviour. METHODS: The primary outcome measure of this non-inferiority trial will be unforeseen N2 disease resulting from lobe-specific mediastinal lymph node dissection. For non-inferiority, the upper limit of the 95% confidence interval of the unforeseen N2 rate in the group without mediastinoscopy should not exceed 14.3% in order to probably have no negative impact on survival. Since this is a non-inferiority trial, both an intention to treat (ITT) and a per protocol (PP) analyses will be done. The ITT and the PP analyses should both indicate non-inferiority before the diagnostic strategy omitting mediastinoscopy will be interpreted as non-inferior to the strategy with mediastinoscopy. Secondary outcome measures include 30-day major morbidity and mortality, the total number of days of hospital care, overall and disease free 2-year survival, generic and disease-specific health related quality of life and cost-effectiveness and cost-utility of staging strategies with and without mediastinoscopy. DISCUSSION: The MEDIASTrial will determine if confirmatory mediastinoscopy can be omitted after tumour negative systematic endosonography in invasive mediastinal staging of patients with resectable NSCLC. TRIAL REGISTRATION: Netherlands Trial Register NL6344/NTR6528 . Registered on 2017 July 06.

Textbook outcome as a composite outcome measure in non-small-cell lung cancer surgery.

OBJECTIVES: Quality assessment is an important element in providing surgical cancer care. The main objective of this study was to develop a new composite measure 'textbook outcome', to evaluate and improve quality of surgical care for patients undergoing a resection for non-small-cell lung cancer (NSCLC). METHODS: All patients undergoing an anatomical resection for NSCLC from 2012 to 2016 registered in the nationwide Dutch Lung Cancer Audit were included in an analysis to assess usefulness of a composite measure as a quality indicator. Based on expert opinion, textbook outcome was defined as having a complete resection (negative resection margins and sufficient lymph node dissection), plus no 30-day or in-hospital mortality, no reintervention in 30 days, no readmission to the intensive care unit, no prolonged hospital stay (<14 days), no hospital readmission after discharge and no major complications. The percentage of patients with a textbook outcome was calculated per hospital. Between-hospital variation in textbook outcome was analysed using case-mix adjustment models. RESULTS: In total, 5513 patients were included in this study. Textbook outcome was achieved in 26.4% of patients. Insufficient lymph node dissection had the most substantial effect on not realizing textbook outcome. If 'sufficient lymph node dissection' was not included as a criterion, textbook outcome would be 60.7%. Case-mix adjusted textbook outcome proportions per hospitals varied between 13.2% and 37.7%. CONCLUSIONS: In contrast to focusing on a single aspect, the composite measure textbook outcome provides insight into comprehensive performance in NSCLC surgery. It can be used to evaluate both individual hospitals and national performance and provides the opportunity to give benchmarked feedback to thoracic surgeons.