BackgroundIn case of suspicious lymph nodes on computed tomography (CT) or fluorodeoxyglucose positron emission tomography (FDG-PET), advanced tumour size or central tumour location in patients with suspected non-small cell lung cancer (NSCLC), Dutch and European guidelines recommend mediastinal staging by endosonography (endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS)) with sampling of mediastinal lymph nodes. If biopsy results from endosonography turn out negative, additional surgical staging of the mediastinum by mediastinoscopy is advised to prevent unnecessary lung resection due to false negative endosonography findings. We hypothesize that omitting mediastinoscopy after negative endosonography in mediastinal staging of NSCLC does not result in an unacceptable percentage of unforeseen N2 disease at surgical resection. In addition, omitting mediastinoscopy comprises no extra waiting time until definite surgery, omits one extra general anaesthesia and hospital admission, and may be associated with lower morbidity and comparable survival. Therefore, this strategy may reduce health care costs and increase quality of life. The aim of this study is to compare the cost-effectiveness and cost-utility of mediastinal staging strategies including and excluding mediastinoscopy.Methods/designThis study is a multicenter parallel randomized non-inferiority trial comparing two diagnostic strategies (with or without mediastinoscopy) for mediastinal staging in 360 patients with suspected resectable NSCLC. Patients are eligible for inclusion when they underwent systematic endosonography to evaluate mediastinal lymph nodes including tissue sampling with negative endosonography results. Patients will not be eligible for inclusion when PET/CT demonstrates ‘bulky N2-N3’ disease or the combination of a highly suspicious as well as irresectable mediastinal lymph node. Primary outcome measure for non-inferiority is the proportion of patients with unforeseen N2 disease at surgery. Secondary outcome measures are hospitalization, morbidity, overall 2-year survival, quality of life, cost-effectiveness and cost-utility. Patients will be followed up 2 years after start of treatment.DiscussionResults of the MEDIASTrial will have immediate impact on national and international guidelines, which are accessible to public, possibly reducing mediastinoscopy as a commonly performed invasive procedure for NSCLC staging and diminishing variation in clinical practice.Trial registrationThe trial is registered at the Netherlands Trial Register on July 6th, 2017 (NTR 6528).Electronic supplementary materialThe online version of this article (10.1186/s12893-018-0359-6) contains supplementary material, which is available to authorized users.

Introduction: Confirmatory mediastinoscopy after negative endosonography findings is advised by the guidelines on patients with resectable NSCLC and suspected intrathoracic nodes on fludeoxyglucose F 18 positron emission tomography-computed tomography. Its role however is under debate owing to its limited nodal metastasis detection rate, morbidity, associated treatment delay, and unknown impact on survival. Methods: Systematic review and meta-analysis of studies on invasive mediastinal staging in patients with (suspected) NSCLC. The Medline, Embase, and Cochrane databases were searched until September 19, 2018, without year or language restrictions. The Quality Assessment Tool for Diagnostic Accuracy Studies, version 2, was used to evaluate the risk of bias and applicability of the included studies. Rates of unforeseen N2 disease were assessed for endobronchial ultrasound and/or endoscopic ultrasound staging strategies with or without confirmatory mediastinoscopy. Additionally, the complication rates of cervical video mediastinoscopy for mediastinal staging of NSCLC were investigated. Results: A total of 5073 articles were found, of which 42 studies or subgroups (covering a total of 3248 patients undergoing the surgical reference standard of treatment) were considered in the analysis. Random effects metaanalysis of endosonography with or without confirmatory mediastinoscopy showed rates of unforeseen N2 disease of 9.6% (95% confidence interval [CI]: 7.8%-11.7%, I 2 ¼ 30%) versus 9.9% (95% CI: 6.3%-15.2%, I 2 ¼ 73%), respectively. Random effects meta-analysis of mediastinoscopy (eight studies [1245 patients in total]) showed a complication rate of 6.0% (95% CI: 4.8%-7.5%), with laryngeal recurrent nerve palsy accounting for 2.8% (95% CI: 2.0%-4.0%). Conclusion: The rate of unforeseen N2 disease after negative endosonography findings was similar in patients undergoing immediate lung tumor resection to those undergoing confirmatory mediastinoscopy first, at the cost of 6.0% rate of complications by mediastinoscopy.

WHAT THIS PAPER ADDSThe peri-operative outcome of carotid endarterectomy is still mostly reported as a composite end point of combined ipsilateral stroke and death rate, both at individual patient level and at hospital level. This paper shows that textbook outcome, a composite measure achieved for an individual patient when all undesirable outcomes are absent, could be added to individual outcome measures to better evaluate hospital performance, especially in surgical interventions with low baseline risk such as carotid interventions.Objective: Composite measures may better objectify hospital performance than individual outcome measures (IOM). Textbook outcome (TO) is an outcome measure achieved for an individual patient when all undesirable outcomes are absent. The aim of this study was to assess TO as an additional outcome measure to evaluate quality of care in symptomatic patients treated by carotid endarterectomy (CEA). Methods: All symptomatic patients treated by CEA in 2018, registered in the Dutch Audit for Carotid Interventions, were included. TO was defined as a composite of the absence of 30 day mortality, neurological events (any stroke or transient ischaemic attack [TIA]), cranial nerve deficit, haemorrhage, 30 day readmission, prolonged length of stay (LOS; > 5 days) and any other surgical complication. Multivariable logistic regression was used to identify covariables associated with achieving TO, which were used for casemix adjustment for hospital comparison. For each hospital, an observed vs. expected number of events ratio (O/E ratio) was calculated and plotted in a funnel plot with 95% control limits. Results: In total, 70.7% of patients had a desired outcome within 30 days after CEA and therefore achieved TO. Prolonged LOS was the most common parameter (85%) and mortality the least common (1.1%) for not achieving TO. Covariates associated with achieving TO were younger age, the absence of pulmonary comorbidity, higher haemoglobin levels, and TIA as index event. In the case mix adjusted funnel plot, the O/E ratios between hospitals ranged between 0.63 and 1.27, with two hospitals revealing a statistically significantly lower rate of TO (with O/E ratios of 0.63 and 0.66). Conclusion:In the Netherlands, most patients treated by CEA achieve TO. Variation between hospitals in achieving TO might imply differences in performance. TO may be used as an additive to the pre-existing IOM, especially in surgical care with low baseline risk such as CEA.

Background: While several observational studies suggested a lower postoperative mortality after minimal invasive endovascular aneurysm repair (EVAR) in patients with a ruptured abdominal aortic aneurysm (RAAA) compared to conventional open surgical repair (OSR), landmark randomized controlled trials have not been able to prove the superiority of EVAR over OSR. Randomized controlled trials contain a selected, homogeneous population, influencing external validity. Observational studies are biased and adjustment of confounders can be incomplete. Instrumental variable (IV) analysis (pseudorandomization) may help to answer the question if patients with an RAAA have lower postoperative mortality when undergoing EVAR compared to OSR. Methods: This is an observational study including all patients with an RAAA, registered in the Dutch Surgical Aneurysm Audit between 2013 and 2017. The risk difference (RD) in postoperative mortality (30 days/in-hospital) between patients undergoing EVAR and OSR was estimated, in which adjustment for confounding was performed in 3 ways: linear model adjusted for observed confounders, propensity score model (multivariable logistic regression analysis), and IV analysis (two-stage least square regression), adjusting for observed and unobserved confounders, with the variation in percentage of EVAR per hospital as the IV instrument. Results: 2419 patients with an RAAA (1489 OSR and 930 EVAR) were included. Unadjusted postoperative mortality was 34.9% after OSR and 22.6% after EVAR (RD 12.3%, 95% CI 8.5e16%). The RD adjusted for observed confounders using linear regression analysis and propensity score analysis was, respectively, 12.3% (95% CI 9.6e16.7%) and 13.2% (95%CI 9.3e 17.1%) in favor of EVAR. Using IV analysis, adjusting for observed and unobserved confounders, RD was 8.9% (95% CI-1.1e18.9%) in favor of EVAR.