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Iatrogenic tracheal rupture is a dangerous complication with potentially high postoperative mortality, mostly influenced by the underlying disease. Early surgical repair must be the preferred treatment.

IntroductionSevere trauma with concomitant chest injury is frequently associated with acute lung failure (ALF). This report summarizes our experience with extracorporeal lung support (ELS) in thoracic trauma patients treated at the University Medical Center Regensburg.MethodsA retrospective, observational analysis of prospectively collected data (Regensburg ECMO Registry database) was performed for all consecutive trauma patients with acute pulmonary failure requiring ELS during a 10-year interval.ResultsBetween April 2002 and April 2012, 52 patients (49 male, three female) with severe thoracic trauma and ALF refractory to conventional therapy required ELS. The mean age was 32 ± 14 years (range, 16 to 72 years). Major traffic accident (73%) was the most common trauma, followed by blast injury (17%), deep fall (8%) and blunt trauma (2%). The mean Injury Severity Score was 58.9 ± 10.5, the mean lung injury score was 3.3 ± 0.6 and the Sequential Organ Failure Assessment score was 10.5 ± 3. Twenty-six patients required pumpless extracorporeal lung assist (PECLA) and 26 patients required veno-venous extracorporeal membrane oxygenation (vv-ECMO) for primary post-traumatic respiratory failure. The mean time to ELS support was 5.2 ± 7.7 days (range, <24 hours to 38 days) and the mean ELS duration was 6.9 ± 3.6 days (range, <24 hours to 19 days). In 24 cases (48%) ELS implantation was performed in an external facility, and cannulation was done percutaneously by Seldinger's technique in 98% of patients. Cannula-related complications occurred in 15% of patients (PECLA, 19% (n = 5); vv-ECMO, 12% (n = 3)). Surgery was performed in 44 patients, with 16 patients under ELS prevention. Eight patients (15%) died during ELS support and three patients (6%) died after ELS weaning. The overall survival rate was 79% compared with the proposed Injury Severity Score-related mortality (59%).ConclusionPumpless and pump-driven ELS systems are an excellent treatment option in severe thoracic trauma patients with ALF and facilitate survival in an experienced trauma center with an interdisciplinary treatment approach. We encourage the use of vv-ECMO due to reduced complication rates, better oxygenation and best short-term outcome.

The receptor for advanced glycation end-products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily. Several ligands binding to RAGE have been identified, including amphoterin. Experimental studies have given rise to the discussion that RAGE and its interaction with amphoterin contribute to tumour growth and metastasis. However, none of the studies considered a differential transcription profile in cancer that might change the interpretation of the study results when comparing RAGE in tumours with histologically normal tissues. Here we show that RAGE is strongly reduced at the mRNA and even more so at the protein level in non-small cell lung carcinomas compared with normal lung tissues. Down-regulation of RAGE correlates with higher tumour (TNM) stages but does not depend on the histological subtypes, squamous cell lung carcinoma and adenocarcinoma. Subsequent overexpression of full-length human RAGE in lung cancer cells (NCI-H358) showed diminished tumour growth under some conditions. While proliferation of RAGE-expressing cells was less than that of cells expressing the cytoplasmic domain deletion mutant DeltacytoRAGE or mock-transfected NCI-H358 in monolayer cultures, RAGE cells also formed smaller tumours in spheroid cultures and in vivo in athymic mice compared with DeltacytoRAGE cells. Moreover, we observed a more epithelial growth of RAGE-expressing, but also of DeltacytoRAGE-expressing, cells on collagen layers, whereas mock NCI-H358 cells kept their tumour morphology. This observation was supported by immunofluorescence analyses demonstrating that RAGE preferentially localizes at intercellular contact sites, independent of expression of the cytoplasmic domain. Thus, down-regulation of RAGE may be considered as a critical step in tissue reorganization and the formation of lung tumours.

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In this review article, state-of-the-art diagnostic tools and innovative treatments of thymoma and thymic carcinoma (TC) are described with special respect to advanced tumour stages. Complete surgical resection (R0) remains the standard therapeutic approach for almost all a priori resectable mediastinal tumours as defined by preoperative standard computed tomography (CT). If lymphoma or germ-cell tumours are differential diagnostic considerations, biopsy may be indicated. Resection status is the most important prognostic factor in thymoma and TC, followed by tumour stage. Advanced (Masaoka-Koga stage III and IVa) tumours require interdisciplinary therapy decisions based on distinctive findings of preoperative CT scan and ancillary investigations [magnetic resonance imaging (MRI)] to select cases for primary surgery or neoadjuvant strategies with optional secondary resection. In neoadjuvant settings, octreotide scans and histological evaluation of pretherapeutic needle biopsies may help to choose between somatostatin agonist/prednisolone regimens and neoadjuvant chemotherapy as first-line treatment. Finally, a multimodality treatment regime is recommended for advanced and unresectable thymic tumours. In conclusion, advanced stage thymoma and TC should preferably be treated in experienced centres in order to provide all modern diagnostic tools (imaging, histology) and innovative therapy techniques. Systemic and local (hyperthermic intrathoracic chemotherapy) medical treatments together with extended surgical resections have increased the therapeutic options in patients with advanced or recurrent thymoma and TC.

Our results indicate an involvement of the anti-apoptotic XIAP in pathogenesis of NSCLC, while hIAP-1 preferentially seems to play an important role in low-stage adenocarcinoma.

The PRAME immunotherapeutic had an acceptable safety profile. All patients had anti-PRAME humoral responses that were not dose related, and 80% of those treated at the highest dose showed a cellular immune response. The dose of 500 μg was selected. However, further development was stopped after negative results with a similar immunotherapeutic in patients with NSCLC.