Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation.

Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential.

Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain.

LRRK2 gain-of-function is considered a major cause of Parkinson's disease (PD) in humans. However, pathogenicity of LRRK2 loss-of-function in animal models is controversial. Here we show that deletion of the entire zebrafish lrrk2 locus elicits a pleomorphic transient brain phenotype in maternal-zygotic mutant embryos (mzLrrk2). In contrast to lrrk2, the paralog gene lrrk1 is virtually not expressed in the brain of both wild-type and mzLrrk2 fish at different developmental stages. Notably, we found reduced catecholaminergic neurons, the main target of PD, in specific cell populations in the brains of mzLrrk2 larvae, but not adult fish. Strikingly, age-dependent accumulation of monoamine oxidase (MAO)-dependent catabolic signatures within mzLrrk2 brains revealed a previously undescribed interaction between LRRK2 and MAO biological activities. Our results highlight mzLrrk2 zebrafish as a tractable tool to study LRRK2 loss-of-function in vivo, and suggest a link between LRRK2 and MAO, potentially of relevance in the prodromic stages of PD.

[Scientific Activity in German Thoracic Surgery, as Measured in Publication Output]. / Wissenschaftliche Aktivität in der deutschen Thoraxchirurgie gemessen an der Publikationsleistung.

Thoracic surgery in Germany is primarily provided in non-university centres with a clinical focus and less at university hospitals. The extent to which scientific activity can be achieved within these different structures is investigated on the basis of publication output.A PubMed analysis was carried out for selected authors (leader in thoracic surgery in Germany) between Jan 2012 to Dec 2021. University hospitals, DKG-certified lung cancer centres (DKG: German Cancer Society) and DGT-certified thoracic centres (DGT: German Society for Thoracic Surgery) were included.An analysis of n = 54 non-university centres (DKG certificate n = 50 and/or DGT certificate n = 22) and n = 36 university hospitals (n = 9 autonomous clinic/department) was performed. A total of n = 2414 publications were identified, with original papers (n = 1776; 74%) and publications focussing on thoracic surgery (n = 1501; 62%) being found most frequently. The publication performance of the non-university centres was n = 599 publications (11/centre) and thus significantly lower than that of the university hospitals (n = 902; 25/clinic; p ≤ 0.001). Significantly higher publication output was confirmed for autonomous (n = 560; 62/clinic) compared to non-autonomous university thoracic surgery (n = 342; 13/clinic; p = 0.003). A 10-year trend was recorded, with almost doubling of publication output from n = 105 (university: n = 63) to n = 203 (university: n = 124) publications/year. The cumulative impact factors (IF) resulted in 2845 IF (52.7 IF/clinic) for non-university centres, 6361 IF (235.6 IF/clinic) for non-autonomous and 2931 IF (325.7 IF/clinic) for autonomous university thoracic surgery.Scientific activities have increased in non-university centres, but above all in university thoracic surgery. These positive developments are in acute danger due to the upcoming political changes (Hospital Structure Act, minimum volumes). Structural changes such as independent university thoracic surgery or cooperation models with non-university centres could offer solutions.

[Management of Malignant Pleural Effusion]. / Management des malignen Pleuraergusses.

Malignant pleural effusion is a common diagnosis in metastasized cancers. It is always of palliative character. Main symptoms are dyspnoea and reduced quality of life. Diagnosis is made by ultrasound-guided puncture of the pleural effusion (cytology) and often video-assisted thoracic surgery with biopsy of the pleural surface (histology). The goal of treatment is a fast, sustainable, minimally invasive, patient-centred therapy that increases quality of life. Besides systemic therapy and best supportive care the patient can be treated with local therapy including either pleurodesis (via drainage or VATS) or an indwelling-pleural catheter (IPC). Decision for one of these procedures is made upon performance index (ECOG), expandability of the lung, prognosis and the patient's wish. For the first technique, the lung must be expandable. The latter one (IPC) can be implanted both with expandable and trapped lung. Both are similarly effective in symptom control.

Wnt/ß-catenin signaling acts cell-autonomously to promote cardiomyocyte regeneration in the zebrafish heart.

Zebrafish can achieve scar-free healing of heart injuries, and robustly replace all cardiomyocytes lost to injury via dedifferentiation and proliferation of mature cardiomyocytes. Previous studies suggested that Wnt/ß-catenin signaling is active in the injured zebrafish heart, where it induces fibrosis and prevents cardiomyocyte cell cycling. Here, via targeting the destruction complex of the Wnt/ß-catenin pathway with pharmacological and genetic tools, we demonstrate that Wnt/ß-catenin activity is required for cardiomyocyte proliferation and dedifferentiation, as well as for maturation of the scar during regeneration. Using cardiomyocyte-specific conditional inhibition of the pathway, we show that Wnt/ß-catenin signaling acts cell-autonomously to promote cardiomyocyte proliferation. Our results stand in contrast to previous reports and rather support a model in which Wnt/ß-catenin signaling plays a positive role during heart regeneration in zebrafish.

Ex vivo expansion of lung cancer-derived disseminated cancer cells from lymph nodes identifies cells associated with metastatic progression.

The cellular basis of the apparent aggressiveness in lung cancer is poorly understood but likely associated with functional or molecular features of disseminated cancer cells (DCCs). DCCs from epithelial cancers are mostly detected by antibodies directed against histogenetic markers such as cytokeratin or EpCAM. It has been argued that marker-negative metastatic founder cells might escape detection. We therefore used ex vivo sphere formation for functional detection of candidate metastasis founders. We generated cell suspensions from 199 LN samples of 131 lung cancer patients and placed them into non-adherent cell culture. Sphere formation was associated with detection of DCCs using EpCAM immunocytology and with significantly poorer prognosis. The prognostic impact of sphere formation was strongly associated with high numbers of EpCAM-positive DCCs and aberrant genotypes of expanded spheres. We also noted sphere formation in patients with no evidence of lymphatic spread, however such spheres showed infrequent expression of signature genes associated with spheres from EpCAM-positive samples and displayed neither typical lung cancer mutations (KRAS, TP53, ERBB1) nor copy number variations, but might be linked to disease progression >5 years post curative surgery. We conclude that EpCAM identifies relevant disease-driving DCCs, that such cells can be expanded for model generation and that further research is needed to clarify the functional and prognostic role of rare EpCAM-negative sphere forming cells.

Cell-fate plasticity, adhesion and cell sorting complementarily establish a sharp midbrain-hindbrain boundary.

The formation and maintenance of sharp boundaries between groups of cells play a vital role during embryonic development as they serve to compartmentalize cells with similar fates. Some of these boundaries also act as organizers, with the ability to induce specific cell fates and morphogenesis in the surrounding cells. The midbrain-hindbrain boundary (MHB) is such an organizer: it acts as a lineage restriction boundary to prevent the intermingling of cells with different developmental fates. However, the mechanisms underlying the lineage restriction process remain unclear. Here, using novel fluorescent knock-in reporters, live imaging, Cre/lox-mediated lineage tracing, atomic force microscopy-based cell adhesion assays and mutant analysis, we analyze the process of lineage restriction at the MHB and provide mechanistic details. Specifically, we show that lineage restriction occurs by the end of gastrulation, and that the subsequent formation of sharp gene expression boundaries in the developing MHB occur through complementary mechanisms, i.e. cell-fate plasticity and cell sorting. Furthermore, we show that cell sorting at the MHB involves differential adhesion among midbrain and hindbrain cells that is mediated by N-cadherin and Eph-ephrin signaling.

Neurogenesis in the inner ear: the zebrafish statoacoustic ganglion provides new neurons from a Neurod/Nestin-positive progenitor pool well into adulthood.

The vertebrate inner ear employs sensory hair cells and neurons to mediate hearing and balance. In mammals, damaged hair cells and neurons are not regenerated. In contrast, hair cells in the inner ear of zebrafish are produced throughout life and regenerate after trauma. However, it is unknown whether new sensory neurons are also formed in the adult zebrafish statoacoustic ganglion (SAG), the sensory ganglion connecting the inner ear to the brain. Using transgenic lines and marker analysis, we identify distinct cell populations and anatomical landmarks in the juvenile and adult SAG. In particular, we analyze a Neurod/Nestin-positive progenitor pool that produces large amounts of new neurons at juvenile stages, which transitions to a quiescent state in the adult SAG. Moreover, BrdU pulse chase experiments reveal the existence of a proliferative but otherwise marker-negative cell population that replenishes the Neurod/Nestin-positive progenitor pool at adult stages. Taken together, our study represents the first comprehensive characterization of the adult zebrafish SAG showing that zebrafish, in sharp contrast to mammals, display continued neurogenesis in the SAG well beyond embryonic and larval stages.

Disseminated cancer cells detected by immunocytology in lymph nodes of NSCLC patients are highly prognostic and undergo parallel molecular evolution.

In melanoma, immunocytology (IC) after sentinel lymph node disaggregation not only enables better quantification of disseminated cancer cells (DCCs) than routine histopathology (HP) but also provides a unique opportunity to detect, isolate, and analyse these earliest harbingers of metachronous metastasis. Here, we explored lymph node IC in non-small cell lung cancer (NSCLC). For 122 NSCLC patients, 220 lymph nodes (LNs) were split in half and prepared for IC and HP. When both methods were compared, IC identified 22% positive patients as opposed to 4.5% by HP, revealing a much higher sensitivity of IC (p < 0.001). Assessment of all available 2,952 LNs of the same patients by HP uncovered additional patients escaping detection of lymphatic tumour spread by IC alone, consistent with the concept of skip metastasis. A combined lymph node status of IC and complete HP on a larger cohort of patients outperformed all risk factors in multivariable analysis for prognosis (p < 0.001; RR = 2.290; CI 1.407-3.728). Moreover, isolation of DCCs and single-cell molecular characterization revealed that (1) LN-DCCs differ from primary tumours in terms of copy number alterations and selected mutations and (2) critical alterations are acquired during colony formation within LNs. We conclude that LN-IC in NSCLC patients when combined with HP improves diagnostic precision, has the potential to reduce total workload, and facilitates molecular characterization of lymphatically spread cancer cells, which may become key for the selection and development of novel systemic therapies. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Visualizing Contralateral Suppression of Hearing Sensitivity via Acoustic and Electric Brainstem Audiometry in Bimodal Cochlear Implant Patients: A Feasibility Study.

INTRODUCTION: The medial olivocochlear reflex (MOCR) is a part of the binaural processing strategies and influences the efferent auditory pathway in normal-hearing individuals. Patients with asymmetric hearing loss often benefit from a bimodal hearing solution with a cochlear implant (CI) and a hearing aid (HA). However, hearing performances may vary with some surprisingly high- or low-performing CI/HA users. A potential role of the MOCR among these patients warrants further investigation. Otoacustics emissions are an established method to visualize the reflex; however, this technique implies some disadvantages. To visualize the MOCR via auditory brainstem response (ABR) could be a promising alternative. METHODS: Twenty-three bimodal CI/HA users were enrolled. Experimental setup was as follows: I. electrical ABR on the CI side was recorded with and without simultaneous contralateral noise signal at the HA side, II. acoustic ABR was recorded on the HA side with and without simultaneous contralateral noise at the CI side. Brainstem thresholds and amplitudes of waveforms I-V with and without contralateral noise were compared. Potential correlations of patient-related factors and hearing performances were analysed. RESULTS: In four individuals, a reduction of brainstem audiometry thresholds could be observed at the acoustic brainstem audiometry. In these cases, results could be reproduced. Summarizing ABR measurements at the HA side of all individuals, no relevant changes of ABR thresholds (dB nHL) or waveform amplitude reductions (nV) could be observed irrespective of the presence or absence of a contralateral suppression signal. CONCLUSION: Threshold changes of acoustic ABR upon presentation of a contralateral suppression signal could not generally be measured in bimodal CI users. However, in a subgroup, a highly reproducible effect was demonstrated if a contralateral suppression signal was applied. A reactivated rather than rehabilitated MOCR may have accounted for this effect in this subgroup. One could speculate that in these patients, bimodal fitting could be affected by the MOCR efferents.

[Robotic-assisted Thoracic Surgery: Currently Available Standard Systems and Future Developments]. / Roboterassistierte Thoraxchirurgie: derzeit verfügbare Standardsysteme und künftige Entwicklungen.

The trend towards performing robotic-assisted operations in thoracic surgery has been increasing in the last decade. The well-known advantages of video-assisted thoracic surgery (VATS) in comparison to the open approach are also valid for robotic surgery, with the addition of a 3D-view camera, wristed instrumentation, and an ergonomic console. The application of robotic technology to thoracic surgical procedures has been shown to be safe and possibly with equivalent oncological outcomes. The Da Vinci Surgical System became the first robotic surgical platform that was commercially available. Several other robotic systems have entered the market in recent years. The current robot systems differ in structure and application.The aim of this review is to describe the current systems in robotic-assisted thoracic surgery (RATS), as well as future developments in RATS.

[Development of Academic Thoracic Surgery in Germany]. / Entwicklung der akademischen Thoraxchirurgie in Deutschland.

In Germany, thoracic surgery is mainly represented at non-university thoracic surgery clinics. It is only established clinically as an independent department or clinic and scientifically as a W2 or W3 professorship at relatively few university hospitals. As a result, it is significantly more difficult to recruit junior specialists and to generate academically active thoracic surgeons as contact persons for researchers from the various fields of life and engineering sciences and for the further development of the field of thoracic surgery, than it is for other surgical specialities. In medical faculties, teaching, research and patient care are on an equal footing. For thoracic surgeons to take on these tasks, concepts are needed to expand and promote academic thoracic surgery in German university medicine. A structured curriculum for academic thoracic surgery can support an academic career in thoracic surgery in addition to mentoring programs, funding opportunities and additional freedom for research or teaching.

Preservation of Adrenoceptor and Endothelin Receptor Mediated Vasoconstriction and of Endothelium-Dependent Relaxation after Cold Storage of Explanted Blood Vessels for ex vivo Analyses.

INTRODUCTION: Adrenoceptor and endothelin (ET) receptor-mediated vasoconstriction as well as endothelium-dependent vasodilation of human saphenous veins were compared before and after 20 h of cold storage. METHODS: Contractile responses to potassium chloride (KCl), norepinephrine (NE), and ET-1 as well as vasodilator responses to acetylcholine (ACh) were evaluated. RESULTS: Storage in HEPES-supplemented Dulbecco's modified Eagle's medium (HDMEM) diminished KCl induced contractile forces to 71% (p = 0.002) and NE induced contractions to 80% (p = 0.037), in contrast to HEPES-supplemented Krebs-Henseleit solution (HKH) and TiProtec solution. KCl-normalized NE contractions were not affected by storage. NE EC50 values were slightly lower (7.1E-8 vs. 7.5E-8, p = 0.019) after storage in HKH, with no changes after storage in the other solutions. Endothelium-dependent responses to ACh were not affected by storage. ET-1 induced contractions were attenuated after storage in HDMEM (77%, p = 0.002), HKH (75%, p = 0.020), and TiProtec (73%, p = 0.010) with no changes in normalized constrictions. ET-1 EC50 values were not affected by storage. CONCLUSION: Loss of contractility after storage in HDMEM may reflect the lower content of dextrose. There was no specific attenuation of adrenoceptor, ET-receptor, or ACh receptor mediated signal transduction after storage in any of the media. HKH or TiProtec are equally suitable cold storage solutions for ex vivo measurements.

Exposure to cisplatin in the operating room during hyperthermic intrathoracic chemotherapy.

PURPOSE: Hyperthermic intrathoracic chemotherapy (HITOC) is an additive, intraoperative treatment for selected malignant pleural tumors. To improve local tumor control, the thoracic cavity is perfused with a cisplatin-containing solution after surgical cytoreduction. Since cisplatin is probably carcinogenic to humans, potential contamination of surfaces and pathways of exposure should be systematically investigated to enable risk assessments for medical staff and thus derive specific recommendations for occupational safety. METHODS: Wipe sampling was performed at pre-selected locations during and after ten HITOC procedures, including on the surgeon's gloves, for the quantitation of surface contaminations with cisplatin. After extraction of the samples with hydrochloric acid, platinum was determined as a marker for cisplatin by voltammetry. RESULTS: High median concentrations of cytostatic drugs were detected on the surgeons' (1.73 pg Cis-Pt/cm2, IQR: 9.36 pg Cis-Pt/cm2) and perfusionists' (0.69 pg Cis-Pt/cm2, IQR: 1.73 pg Cis-Pt/cm2) gloves. The display of the perfusion device showed partially elevated levels of cisplatin up to 4.92 pg Cis-Pt/cm2 and thus could represent an origin of cross-contamination. In contrast, cisplatin levels on the floor surfaces in the area of the surgeon and the perfusion device or in the endobronchial tube were relatively low. CONCLUSION: With a correct use of personal protective equipment and careful handling, intraoperative HITOC appears to be safe to perform with a low risk of occupational exposure to cisplatin.

Evaluation of hearing preservation in adults with a slim perimodiolar electrode.

PURPOSE: Numerous endeavors have been undertaken to preserve hearing in cochlear implant (CI) patients. Particularly, optimization of electrode array design aims at preservation of residual hearing (RH). This study examines whether a slim perimodiolar (PM) electrode array could bear the capability to preserve hearing. METHODS: A total of 47 patients underwent cochlear implantation receiving the PM electrode. (i) Patients with pure tone audiogram (PTA) thresholds better than 85 dB and/or hearing loss for Freiburg speech test numbers less than 60 dB and more than 50% maximum monosyllabic understanding were assigned to the RH group (n = 17), while all others belonged to the noRH group (n = 30). (ii) Another group implanted with a slim straight, lateral wall (LW) electrode was recruited for comparison. RESULTS: We compared 17 RH-30 noRH patients all receiving the PM electrode. RH in PM recipients decreased faster than in LW recipients. No significant differences were observed between both (RH v/s noRH) groups in NRT thresholds, Freiburg speech test and A§E® phonemes. Analogous satisfaction levels were indicated through the questionnaires in terms of sound quality, hearing in silence, noise and directional hearing in both groups. CONCLUSIONS: The results suggest that hearing preservation is influenced not only by electrode shape but various factors. This study opens an avenue for further investigations to elucidate and enumerate the causes for progressive hearing loss.

[Modern Perioperative Care Concepts in Thoracic Surgery: Enhanced Recovery After Thoracic Surgery (ERATS)]. / Moderne perioperative Versorgungskonzepte in der Thoraxchirurgie: Enhanced Recovery After Thoracic Surgery (ERATS).

In modern perioperative care concepts, multimodal ERAS (Enhanced Recovery After Surgery) is a multimodal perioperative treatment concept for improving postoperative recovery of surgical patients after an operation. This is managed by the so-called ERAS Society and through which hospitals can also be officially certified. The focus of the ERAS concept is on uniform patient care from admission to discharge, with the aim of improving perioperative processes by implementing evidence-based protocols involving a multidisciplinary treatment team. In 2019, ERAS guidelines were published for the first time by the European Society of Thoracic Surgery (ESTS), in cooperation with the ERAS Society, for specific lung resection procedures, and these identified a total of 45 graduated recommendations or Enhanced Recovery Pathways (ERP). The implementation of ERAS concepts in thoracic surgery (ERATS = Enhanced Recovery After Thoracic Surgery) is intended to establish standardised perioperative procedures based on study results and/or expert recommendations. These recommendations take into account organisational aspects as well as thoracic surgical and anaesthesiological procedures, with the overriding goal of creating a structured treatment plan tailored to the patient. All these measures should result in a multimodal overall concept, which should primarily lead to an improved outcome after elective thoracic surgery and secondarily to shorter hospital stays with correspondingly lower costs.This review article describes basic ERAS principles and provides a compact presentation of the most important European ERAS recommendations from the authors' point of view, together with typical obstacles to the implementation of the corresponding ERATS program in German thoracic surgery.

Turning to the negative: attention allocation to emotional faces in adolescents with dysregulation profile-an event-related potential study.

Patients with irritability, temper outbursts, hyperactivity and mood swings often meet the dysregulation profile (DP) of the Child Behavior Checklist (CBCL) or the Strengths and Difficulties Questionnaire (SDQ), which have been investigated over the past few decades. While the DP has emerged as a transdiagnostic marker with a negative impact on therapeutic outcome and psychosocial functioning, little is known about its underlying mechanisms such as attention and emotion regulation processes. In this study, we tested whether adolescent psychiatric patients (n = 27) with the SDQ-DP show impaired emotional face processing for task-irrelevant stimuli compared to psychiatric patients without the SDQ-DP (n = 30) and non-clinical adolescents (n = 21). Facial processing was tested with event-related potential (ERP) measures known to be modulated by attention (i.e., P1, N1, N170, P2, and Nc) during a modified Attention Network Task, to which task-irrelevant emotional stimuli (sad, fearful, and neutral faces) were added prior to the actual trial. The results reveal group differences in the orienting and in the conflicting network. Patients with DP showed a less efficient orienting network and the clinical control group showed a less efficient conflicting network. Moreover, patients with the dysregulation profile had a shorter N1/N170 latency than did the two control groups, suggesting that dysregulation in adolescents is associated with a faster but less arousing encoding of (task-irrelevant) emotional information and less top-down control.

Surgical Cytoreduction and HITOC for Thymic Malignancies with Pleural Dissemination.

BACKGROUND: Objective of this study was to assess postoperative morbidity and mortality as well as recurrence-free and overall survival in patients with thymic malignancies and pleural dissemination undergoing surgical cytoreduction and hyperthermic intrathoracic chemotherapy (HITOC). METHODS: Retrospective study between September 2008 and December 2017 with follow-up analysis in May 2018. RESULTS: A total of 29 patients (male: n = 17) with thymic malignancies and pleural spread (primary stage IVa: n = 11; pleural recurrence: n = 18) were included. Surgical cytoreduction was performed via pleurectomy/decortication (P/D; n = 11), extended P/D (n = 15), and extrapleural pneumonectomy (EPP; n = 3). These procedures resulted in 25 (86%) patients with macroscopically complete (R0/R1) resection. Intraoperative HITOC was performed for 60 minutes at 42°C either with cisplatin (100 mg/m2 body surface area [BSA] n = 8; 150 mg/m2 BSA n = 6; 175 mg/m2 BSA n = 1) or with a combination of cisplatin (175 mg/m2 BSA)/doxorubicin (65 mg; n = 14). Postoperative complications occurred in nine patients (31%). Cytoprotective therapy resulted in lower postoperative creatinine levels (p = 0.036), and there was no need for temporary dialysis in these patients. The 90-day mortality rate was 3.4%, as one patient developed multiple organ failure. While recurrence-free 5-year survival was 54%, an overall 5-year survival rate of 80.1% was observed. Survival depended on histological subtype (p = 0.01). CONCLUSION: Surgical cytoreduction with HITOC is feasible in selected patients and offers encouraging survival rates. The application of cytoprotective agents appears to be effective for the prevention of postoperative renal insufficiency.

[Five Years PLEURATUMOR Register of the German Society of Thoracic Surgery]. / Fünf Jahre PLEURATUMOR-Register der Deutschen Gesellschaft für Thoraxchirurgie.

BACKGROUND: Since 01.01.2015, the nationwide "PLEURATUMOR Register of the German Society of Thoracic Surgery (DGT)" has documented the most relevant parameters of patients with primary and secondary malignant pleural diseases receiving thoracic surgery in Germany. This online database is intended to record both primary and recurrent diseases. In particular, the registry focuses on the documentation of patients with pleural carcinosis, malignant pleural mesothelioma and tumours of the thymus with pleural dissemination. METHODS: A structured evaluation of all patients documented up to and including December 2019 was carried out. RESULTS: At this time, 33 departments participated in the PLEURATUMOR Register and 670 patients have been recorded. Of these patients, 522 data sets were complete and 516 patients received surgical treatment. Most patients were documented in 2017 (n = 135; 26.2%), and in 2019 (n = 72; 14%). With 317 listed patients (61.4%), pleural carcinosis was the most frequently reported pleural tumour, followed by malignant pleural mesothelioma (n = 175; 33.9%) and thymoma/thymic carcinoma with pleural metastases (n = 11; 2.1%). The majority of patients (n = 499; 96.7%) were treated because of an initial manifestation. The most frequently documented procedure was VATS-talcum pleurodesis (n = 204; 39.5%). In 69 patients (13.4%) hyperthermic intrathoracic chemotherapy was performed after cytoreductive surgery. Postoperative complications occurred in 107 patients (20.7%); in 35 cases (6.8%) surgical revision was necessary. The overall 30-day mortality was 8.3% (n = 43). CONCLUSION: Due to the consistent data entry of the participating clinics, a representative dataset of pleural tumour diseases could be recorded. In the future, we hope for consistent continuation of data entry and the initiation of register-based studies.

[Extended Resection of Locally Advanced Thymic Tumours in Stage III]. / Erweiterte Resektionsverfahren bei lokal fortgeschrittenen Tumoren des Thymus im Stadium III.

In the treatment of locally advanced thymic tumours, specific diagnostic testing is required, with a multimodal therapeutic approach consisting of surgery, radio- and/or chemotherapy. The complete resection of the tumour represents the most important prognostic factor with regard to recurrence-free and long-term survival. Local invasive growth of malignant thymic tumours into neighbouring mediastinal structures is classified as Masaoka-Koga stage III. Surgical resection can be performed primarily or after induction therapy, depending on the extent of the tumour. However, in some cases these tumours must be classified as non-resectable, so that only palliative radio-/chemotherapy remains as therapeutic option. TNM classification for malignant thymic tumours has been recently introduced. This resembles the established Masaoka-Koga classification in many aspects, but also includes some therapy-relevant changes. A differentiation is made between stages IIIA and IIIB, with the aim of assessing the resectability of advanced thymic tumours in a more differentiated manner and consequent planning of the therapy concept. Besides the thymus, thymoma, perithymic tissue, mediastinal pleura (stage I) or pericardium (stage II), all infiltrated structures should be removed "en bloc", if possible in stage III tumours. While the lung, brachiocephalic vessels or extrapericardial pulmonary vessels can still be resected and reconstructed if necessary, infiltration of the aorta or intrapericardial pulmonary vessels often limits macroscopically complete resection.