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Abstract Thymic epithelial tumors (TET) are a group of rare neoplasms of the anterior mediastinum comprising thymomas and thymic carcinomas. The carcinogenesis of TET is mostly unknown. Many studies, mostly retrospective case series, have tried to establish prognostic factors in TET. TET is a very heterogeneous group of tumors with many subtypes for which diagnosis and treatment remains a very challenging task. Despite the disparities among retrospective studies, there are some prognostic factors that are more pertinent such as the completeness of resection, TNM stage and the Masaoka‐Koga classification. On the other hand, the identification of different genetic pathways that result in the pathogenesis of TET represents a fascinating field of study that could possibly lead to the development of new targeted therapies. The aim of this review is to discuss the different prognostic factors and genetic markers of TET. The meticulous use of national and international databases could provide sufficient number of patients in order to draw more valid conclusions.

Pathology and radiology are complimentary tools, and their joint application is often crucial in obtaining an accurate diagnosis in non-neoplastic pulmonary diseases. However, both come with significant limitations of their own: Computed Tomography (CT) can only visualize larger structures due to its inherent–relatively–poor resolution, while (histo) pathology is often limited due to small sample size and sampling error and only allows for a 2D investigation. An innovative approach of inflating whole lung specimens and subjecting these subsequently to CT and whole lung microCT allows for an accurate matching of CT-imaging and histopathology data of exactly the same areas. Systematic application of this approach allows for a more targeted assessment of localized disease extent and more specifically can be used to investigate early mechanisms of lung diseases on a morphological and molecular level. Therefore, this technique is suitable to selectively investigate changes in the large and small airways, as well as the pulmonary arteries, veins and capillaries in relation to the disease extent in the same lung specimen. In this perspective we provide an overview of the different strategies that are currently being used, as well as how this growing field could further evolve.

Abstract Background In 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/design This 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. Discussion Results 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 registration The trial is registered at the Netherlands Trial Register on July 6th, 2017 (NTR 6528).

Abstract Subsequent to the widespread use of multidetector computed tomography and growing interest in lung cancer screening, small pulmonary nodules are more frequently detected. The differential diagnosis for a solitary pulmonary nodule is extremely broad and includes both benign and malignant causes. Recognition of early lung cancers is vital, since stage at diagnosis is crucial for prognosis. Estimation of the probability of malignancy is a challenging task, but crucial for follow-up and further work-up. In addition to the clinical setting and metabolic assessment, morphological assessment on thin-section computed tomography is essential. Size and growth are key factors in assessment of the malignant potential of a nodule. The likelihood of malignancy positively correlates with nodule diameter: as the diameter increases, so does the likelihood of malignancy. Although there is a considerable overlap in the features of benign and malignant nodules, the importance of morphology however should not be underestimated. Features that are associated with benignity include a perifissural location and triangular morphology, internal fat and benign calcifications. Malignancy is suspected in nodules presenting with spiculation, lobulation, pleural indentation, vascular convergence sign, associated cystic airspace, bubble-like lucencies, irregular air bronchogram, and subsolid morphology. Nodules often show different features and combination of findings is certainly more powerful. Teaching points • Size of a pulmonary nodule is important, but morphological assessment should not be underestimated. • Lung nodules should be evaluated on thin section CT, in both lung and mediastinal window setting. • Features associated with benignity include a triangular morphology, internal fat and calcifications. • Spiculation, pleural retraction and notch sign are highly suggestive of a malignant nature. • Complex features (e.g. bubble-like lucencies) are highly indicative of a malignant nature.

According to the eighth edition of the tumor–node–metastasis classification, stage III non-small cell lung cancer is subdivided into stages IIIA, IIIB, and IIIC. They represent a heterogeneous group of bronchogenic carcinomas with locoregional involvement by extension of the primary tumor and/or ipsilateral or contralateral lymph node involvement. Surgical indications have not been definitely established but, in general, long-term survival is only obtained in those patients in whom a complete resection is obtained. This mini-review mainly focusses on stage IIIA disease comprising patients with locoregionally advanced lung cancers. Different subcategories of N2 involvement exist, which range from unexpected N2 disease after thorough preoperative staging or “surprise” N2, to bulky N2 involvement, mostly treated by chemoradiation, and finally, the intermediate category of potentially resectable N2 disease treated with a combined modality regimen. After induction therapy for preoperative N2 involvement, best surgical results are obtained with proven mediastinal downstaging when a lobectomy is feasible to obtain a microscopic complete resection. However, no definite, universally accepted guidelines exist. A relatively new entity is salvage surgery applied for recurrent disease after full-dose chemoradiation when no other therapeutic options exist. Equally, only a small subset of patients with T4N0-1 disease qualify for surgical resection after thorough discussion within a multidisciplinary tumor board on the condition that a complete resection is feasible. Targeted therapies and immunotherapy have recently become part of our therapeutic armamentarium, and it might be expected that they will be incorporated in current regimens after careful evaluation in randomized clinical trials.

Recently, major changes have occurred in the staging, diagnosis, and treatment of early stage lung cancer. By screening high-risk populations, we are now able to detect lung cancers at an early stage, but the false-positive rate is high. A new pathological classification was published in 2011 and fully incorporated in the 2015 World Health Organisation (WHO) Classification of Tumours of the Lung, Pleura, Thymus, and Heart. The new eighth edition of the tumour–node–metastasis (TNM) staging system has been fully published and will be in use from January 2017. T1 lesions are subdivided into T1a, T1b, and T1c lesions corresponding to lung cancers up to 10 mm, between 11 and 20 mm, and between 21 and 30 mm, respectively. To determine the size, only the solid part on computed tomographic scanning of the chest and the invasive part on pathological examination will be considered. Prognosis is significantly better for the smallest lesions. For some specific subgroups, sublobar resection may be oncologically valid and yield good long-term outcome, but the results of recently performed randomised trials are awaited.

Atherosclerosis remains the leading cause of death and disability in our Western society. To investigate whether the dynamics of leukocyte (sub)populations could be predictive for plaque inflammation during atherosclerosis, we analyzed innate and adaptive immune cell distributions in blood, plaques, and lymphoid tissue reservoirs in apolipoprotein E-deficient (ApoE−/−) mice and in blood and plaques from patients undergoing endarterectomy. Firstly, there was predominance of the CD11b+ conventional dendritic cell (cDC) subset in the plaque. Secondly, a strong inverse correlation was observed between CD11b+ cDC or natural killer T (NKT) cells in blood and markers of inflammation in the plaque (including CD3, T-bet, CCR5, and CCR7). This indicates that circulating CD11b+ cDC and NKT cells show great potential to reflect the inflammatory status in the atherosclerotic plaque. Our results suggest that distinct changes in inflammatory cell dynamics may carry biomarker potential reflecting atherosclerotic lesion progression. This not only is crucial for a better understanding of the immunopathogenesis but also bares therapeutic potential, since immune cell-based therapies are emerging as a promising novel strategy in the battle against atherosclerosis and its associated comorbidities. The cDC-NKT cell interaction in atherosclerosis serves as a good candidate for future investigations.

The role of surgery in stage ⅢA-N2 non-small cell lung cancer (NSCLC) remains controversial. Most important prognostic factors are mediastinal downstaging and complete surgical resection. Different restaging techniques exist to evaluate response after induction therapy and these are subdivided into non-invasive, invasive and alternative or minimally invasive techniques. In contrast to imaging or functional studies, remediastinoscopy provides pathological evidence of response after induction therapy. Although technically more challenging than a first procedure, remediastinoscopy can select patients for subsequent thoracotomy and provides prognostic information. An alternative approach consists of the use of minimally invasive staging procedures as endobronchial or endoscopic esophageal ultrasound to obtain an initial proof of mediastinal nodal involvement. Mediastinoscopy is subsequently performed after induction therapy to evaluate response. In this way, a technically more difficult remediastinoscopy can be avoided. Stage ⅢA-N2 NSCLC represents a heterogenous spectrum of locally advanced disease and different subsets exist. When N2 disease is discovered during thoracotomy after negative, careful preoperative staging a resection should be performed if this can be complete. Postoperative radiotherapy will decrease local recurrence rate but not overall survival. Adjuvant chemotherapy increases survival and is presently recommended in these cases. Most patients with pathologically proven N2 disease detected during preoperative work-up will be treated by induction therapy followed by surgery or radiotherapy.In two large, recently completed, phase Ⅲ trials there was no difference in overall survival between the surgical and radiotherapy arm, but in one trial there was a difference in progression-free survival in favor of the surgical arm. In the surgery arm the rate of local recurrences was also lower in both trials. Surgical resection may be recommended in those patients with proven mediastinal downstaging after induction therapy who can preferentially be treated by lobectomy. Pneumonectomy has a significantly higher mortality and morbidity rate, especially after induction chemoradiotherapy. Patients with bulky N2 disease are mostly treated with combined chemoradiotherapy although the precise treatment scheme has not been determined yet.