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The value of thymectomy in the treatment of non-thymomatous myasthenia gravis has been controversially discussed. The relatively low incidence and prevalence of this disease, the inconsistent documentation in various studies and the necessity of a long-term follow-up to assess the therapeutic effects has made the generation of valid data difficult. The publication in 2016 of the MGTX trial in the New England Journal of Medicine delivered the first randomized controlled data in which patients aged 18-65 years with generalized myasthenia gravis and positive for acetylcholine receptor antibodies showed a significant benefit after surgical resection of the thymus via median sternotomy. Despite a lack of validation of the advantages of thymectomy by minimally invasive surgery from randomized controlled studies, this technique seems to positively influence the outcome of certain patient groups in a similar way. Video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS) using subxyphoidal and transcervical access routes showed not only esthetic advantages but also showed no relevant inferiority in the influence on clinical outcomes of myasthenia gravis compared to median sternotomy; however, not only the benefits and the esthetic results show differences but also the advantages in the various subtypes of myasthenia gravis show divergent prospects of success with respect to remission. The clinical spectrum of myasthenia is heterogeneous with respect to the occurrence of antibodies, the body region affected and the age of the patient at first diagnosis. Ultimately, thymectomy is an effective causal treatment of myasthenia gravis.Der Stellenwert der Thymektomie in der Therapie der thymomfreien Myasthenia gravis blieb bis vor einiger Zeit umstritten. Die relativ geringe Inzidenz und Prävalenz der Erkrankung, die uneinheitliche Dokumentation in den verschiedenen Studien sowie die notwendige Langzeitbeobachtung zur Erfassung therapeutischer Effekte erschwerten das Generieren valider Daten. Die Veröffentlichung des MGTX-Trials 2016 im New England Journal of Medicine lieferte die ersten randomisiert-kontrollierten Daten, nach denen Patienten mit Acetylcholin-Rezeptor-Antikörper-positiver generalisierter Myasthenia gravis im Alter von 18 bis 65 Jahren von der chirurgischen Resektion des Thymus über eine mediane Sternotomie profitieren. Trotz fehlender Validierung des Vorteils der Thymektomie über minimal-invasive Techniken durch randomisiert-kontrollierte Studien scheinen diese das Outcome bestimmter Patientengruppen in ähnlicher Form positiv zu beeinflussen. So haben videoassistiert-thorakoskopische, roboterassistierte, subxiphoidale und transzervikale Zugangswege nicht nur ästhetische Vorteile, sondern zeigen in der Beeinflussung des Krankheitsverlaufs der Myasthenia gravis keine relevante Unterlegenheit gegenüber der medianen Sternotomie. Doch nicht nur der Nutzen und das ästhetische Ergebnis differieren, sondern auch die Erfolgsaussichten im Hinblick auf die Remission sind bei den Unterformen der Myasthenia gravis unterschiedlich. Die heterogene Gruppe der Myasthenien unterscheidet sich bezüglich des Auftretens von Autoantikörpern, der betroffenen Körperregionen und des Alters der Patienten bei Erstdiagnose. Schließlich ist die Thymektomie eine wirksame kausale Therapie der Myasthenia gravis.

The immune response against cancer is orchestrated by various parameters and site-dependent specificities have been poorly investigated. In our analyses of ten different cancer types, we describe elevated infiltration by regulatory T cells as the most common feature, while other lymphocyte subsets and also expression of immune-regulatory molecules on tumor-infiltrating lymphocytes showed site-specific variation. Multiparametric analyses of these data identified similarities of renal and liver or lung with head and neck cancer. Co-expression of immune-inhibitory ligands on tumor cells was most frequent in colorectal, lung and ovarian cancer. Genes related to antigen presentation were frequently dysregulated in liver and lung cancer. Expression of co-inhibitory molecules on tumor-infiltrating T cells accumulated in advanced stages while T-cell abundance was related to enhanced expression of genes related to antigen presentation. Our results promote evaluation of cancer-specific or even personalized immunotherapeutic combinations to overcome primary or secondary resistance as major limitation of immune-checkpoint inhibition.

The optimal surgical reconstruction of chest wall defects especially in the context of posttraumatic, oncological and congenital etiologies has a large impact on the recovery of the patients. Regardless of the etiology, various complications, such as a generally impaired respiratory physiology in an unstable thorax or decreased pulmonary clearance associated with acute and chronic pulmonary infections, may impair the recovery of affected patients. The postoperative occurrence of an intrathoracic dead space may lead to a difficult to treat empyema. Each thoracic wall defect must be accurately assessed and treated according to size, depth and location on the chest. The complexity of this condition and the resulting complications require the highest degree of surgical care which should be interdisciplinary both preoperatively and postoperatively.

Background: Programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) immune checkpoint inhibitors have been approved for monotherapy of metastatic nonsmall cell lung cancer (mNSCLC) depending on tumour cells' PD-L1 expression. Pleural effusion is common in mNSCLC. The significance of immunocytochemistry PD-L1 analysis from pleural effusion samples is unclear. Aim: The aim of the study was to analyse the sensitivity regarding immunocytochemistry PD-L1 analysis of pleural effusion in NSCLC as compared to immunohistochemistry of pleural biopsies. Patients and Methods: Fifty consecutive subjects (17 female, median age 72.5 years, seven never-smokers) were enrolled in this prospective controlled two-centre study. Inclusion criteria were pleural effusion, suspected or known lung cancer, indication for pleural puncture and thoracoscopy, and written informed consent. Immunocytochemistry and immunohistochemistry PD-L1 analyses were performed with the Dako-PDL1-IHC-22C3pharmDx assay. Analysis for sensitivity, specificity, and positive and negative predictive value was performed for PD-L1 detection from pleural effusion. Results: 50 subjects underwent pleural puncture and thoracoscopy. Pathological diagnoses were lung cancer (48), lymphoma (1) and mesothelioma (1). Sensitivity, specificity, positive predictive value and negative predictive value of PD-L1-testing with expression ≥50% defined as positive were 100% (95% CI 46–100%), 63% (36–84%), 45% (18–75%) and 100% (66–100%), and with expression ≥1% defined as positive 86% (56–97%), 43% (12–80%), 75% (47–92%) and 60% (17–93%). Conclusion: PD-L1 analysis in tumour-positive pleural effusion samples shows a very high sensitivity and negative predictive value, especially regarding PD-L1 expression levels ≥50% (European Medicines Agency approval). Negative results are reliable and help in the decision against a first-line checkpoint inhibitor monotherapy. However, a 1% cut-off level (United States Food and Drug Administration approval) leads to a markedly lower negative predictive value, making other invasive procedures necessary (NCT02855281)., PD-L1 analysis in tumour-positive pleural effusion samples is characterised by a very high sensitivity and negative predictive value. Negative results seem very reliable and could thus help in the decision against a first-line checkpoint inhibitor therapy. https://bit.ly/2GPCLYS

Radical lymphadenectomy is crucial in operations for non-small cell lung cancer (NSCLC). Usually pN1 and pN2 lymph nodes are affected consecutively (N1N2). Nevertheless, pN2 metastases may also occur in the absence of pN1 as skip-N2 metastases (N0N2). Here we compare the long-term survival of N1N2- and N0N2 patients.464 patients underwent surgery for NSCLC at our institution between 2012 and 2017. We retrospectively reviewed data of pN2 stage patients (n = 68). Patients with N1N2 (n = 39) were compared to N0N2 (n = 29) patients. 1-, 3-and 5-year survival rates were measured. Survival was assessed by Kaplan-Meier curves and the cox proportional hazards model was used to identify prognostic factors for overall survival. All patients received adjuvant chemoradiation therapy according to European guidelines.The baseline characteristics did not differ between groups. We observed no differences in the histology, localization, or gender in our cohort. N0N2 patients showed significantly better 1- (N1N2: 82.4% vs. N0N2 100%; p = 0.001), 3- (14.7% vs. 63.6%; p=0.001) and 5-year (9.4% vs. 43.8%; p = 0.001) survival rates. Tumor size (Hazard ratio (HR) 1.46, Confidence interval (CI 95%) 1.03-2.04; p = 0.03) and the occurrence of N1N2 (HR 4.26, CI 2.04-8.91; p 0.0001) were independent prognostic factors for worse long-term survival. The Kaplan-Meier curves showed a reduced overall survival for N1N2 patients (log-rank N1N2, N0N2 p 0.0001).N1N2 patients have a significantly worse prognosis compared to N0N2 patients. This will aid to classify the heterogeneous pN2-NSCLC patient population more precisely. Further, multimodal therapy should be considered for N1N2 patients.

The significance of postoperatively diagnosed Lymphangiosis Carcinomatosa (L1) as an independent risk factor for long-term survival in Non-Small Cell Lung Cancer (NSCLC) remains controversial. We analyzed the effect of L1 on postoperative survival in stage I, II and III NSCLC-patients.We investigated all consecutive patients with NSCLC between January 2012 and December 2019 who underwent an anatomical resection and radical lymphadenectomy at our institute. L1-were compared to L0-patients. All patients received adjuvant chemotherapy in accordance with European guidelines. 3- and 5- year survival rates and median-survival were assessed. To investigate whether L1 is an independent risk factor, we carried out a multivariate cox regression and a pair-match analysis looking at different properties such as TNM.A total of 641 patients (L0: 74%; L1: 26%) were analyzed. Baseline characteristics were comparable between groups. The mean age was 65.3 ± 10.2 years and 64.9 ± 9.4 years in the L0 and L1-groups respectively (p-value = 0.703). 58.5% of L0-patients were male (L1: 62.7%; p-value = 0.351). Overall survival in the L1-group was significantly shorter compared to the L0-group (L1: 42.3 ± 2.8; L0: 67.6 ± 2.1 months; p-value0.0001). We confirmed this finding in a pair-matched analysis (L0: 73.9 ± 4.7 months; L1: 42.2 ± 4.2; p-value = 0.009). 3- and 5-year survival were significantly shorter for L1-patients (3-year: L0: 65.9%; L1: 35.9%; p-value0.0001) (5-year: L0: 34.9%; L1: 7.5%; p-value0.0001).L1 is an independent risk factor for long-term survival of patients with NSCLC. This cohort supports that the L0/L1 status should be included in pathological reports. We suggest to further include L0/L1-status in guideline recommendations for NSCLC patients.

Zusammenfassung Hintergrund Patienten mit kolorektalem Karzinom sind häufig von Leber- und Lungenmetastasen betroffen. Neben Systemtherapien eignet sich für Patienten nach vollständiger Primärtumor- und potenzieller Lebermetastasenresektion die Lungenmetastasenchirurgie als therapeutisches Konzept. Material und Methoden Es erfolgte eine systematische Literaturrecherche unter Berücksichtigung aller Studien, die ab dem 01. 01. 2010 publiziert worden sind. In die deskriptive Analyse wurden Studien eingeschlossen, die über mindestens 100 Patienten mit Lungenmetastasektomie berichteten und deren Operationszeitraum frühestens am 01. 01. 2000 begann. Aus den Studien wurden operative Daten, Überlebensdaten und Prognosefaktoren extrahiert. Ergebnisse Elf Studienkohorten mit insgesamt 2891 Patienten konnten in die Analyse eingeschlossen werden. In den meisten Fällen wurde eine vollständige Resektion aller Metastasen erreicht und dabei subsegmentale den anatomischen Resektionsverfahren vorgezogen. Bei 2,3 – 18,2% der Patienten zeigten sich intrathorakale Lymphknotenmetastasen. Die postoperative Mortalität bewegte sich zwischen 0 und 0,5%. Der mediane Nachbeobachtungszeitraum erstreckte sich in den Fallserien von 27,5 bis zu 65,1 Monaten. Die Lungenmetastasenchirurgie war in den Studienkohorten mit 5-Jahres-Überlebensraten von 53 – 75,5% verbunden. Das 5-Jahres-Progressionsfreie-Überleben variierte zwischen 33 und 50,9%. Intrathorakale Rezidive traten in 25,2 – 42,9% der Patienten auf. Die Remetastasektomie resultierte in 5-Jahres-Überlebensraten von 49 – 75,5%. Die Analyse von Prognosemodellen offenbarte, dass die Metastasenanzahl, -größe und -verteilung eine untergeordnete prognostische Relevanz zu besitzen scheinen. Ein erhöhter CEA-Serumspiegel vor Metastasektomie und intrathorakale Lymphknotenmetastasen bedeuteten in mehreren Studien einen prognostischen Nachteil, nichtsdestotrotz können auch diese Patienten von der Lungenmetastasenchirurgie profitieren. Schlussfolgerungen Für Patienten mit kolorektalem Karzinom und isolierter Lungen- oder kombinierter Leber- und Lungenmetastasierung sollte bei gewährleisteter Resektabilität die Metastasektomie die Therapie der Wahl sein. Die Lungenmetastasenchirurgie sollte durch eine Lymphknotenresektion ergänzt werden, um potenzielle Lymphknotenmetastasen zu entfernen. Patienten mit isolierten intrathorakalen Rezidiven sollte eine Remetastasektomie angeboten werden.

Zusammenfassung Hintergrund Weichteil- und Osteosarkome sind häufig mit Lungenmetastasen vergesellschaftet. Patienten sind für eine kurative Metastasektomie geeignet, wenn der Primärtumor erfolgreich reseziert worden ist, sie lediglich pulmonale Metastasen aufweisen und die funktionelle Operabilität sowie die vollständige Metastasenresektion gewährleistet sind. Material und Methoden Systematische Literaturrecherche und qualitative Analyse aller ab dem 01.01.2010 publizierten Fallserien über Patienten nach vollständiger Sarkomresektion und anschließender Lungenmetastasenchirurgie. Zielparameter waren operative Befunde, Überlebensdaten und Prognosefaktoren. Ergebnisse Die Lungenmetastasenchirurgie ermöglicht ein medianes Postmetastasektomieüberleben von 8,76 bis 69,9 Monaten. Postoperativ werden nach Metastasektomie 5-Jahres-Überlebensraten zwischen 21,7 und 56,8% erreicht, dabei hängt die Prognose maßgeblich von der vollständigen Resektion aller Lungenmetastasen ab. Intrapulmonale Rezidive können nach kritischer Indikationsstellung reseziert werden und mit einer günstigen Prognose verbunden sein. Schlussfolgerungen Für selektionierte Patienten mit Osteosarkomen und isolierter Lungenmetastasierung sollte die Metastasektomie die Therapie der Wahl sein. Patienten mit Weichteilsarkomen und isolierter pulmonaler Metastasierung können bei richtiger Indikationsstellung von einem chirurgischen Eingriff profitieren.

Breast carcinoma with pulmonary metastasis can be treated locally or systemically. Following primary tumour resection patients with isolated, completely resectable pulmonary nodules and definite functional operability can be offered lung metastasis resection. Following metastasectomy a median survival of 32 to 96.6 months can be achieved with corresponding five-year survival rates between 30.8 and 54.4%. The procedure is associated with a mortality rate of 0 to 3%. The most important independent prognostic factor for long-term survival is complete resection of all lung lesions. The configuration and pattern of metastasis as well as disease-free interval, hormone and HER2/neu receptor status also appear to influence prognosis, but are of lesser importance. Intrapulmonary recurrence of metastases may, after careful selection on a case-by-case basis, also be treated operatively. In some cases this is associated with a favourable long-term prognosis. Pulmonary metastasectomy should be the treatment of choice for selected patients with metastatic breast carcinoma.Das pulmonal metastasierte Mammakarzinom kann systemisch oder lokal therapiert werden. Nach erfolgter Primärtumorresektion können Patientinnen mit isolierten, vollständig resektablen Lungenrundherden und sichergestellter funktioneller Operabilität einer Lungenmetastasektomie zugeführt werden. Nach Metastasenresektion wird ein medianes Überleben von 32 bis 96,6 Monaten erreicht, korrespondierende 5-Jahres-Überlebensraten liegen zwischen 30,8 und 54,4%. Der Eingriff ist mit einer Mortalität von 0 – 3% verbunden. Der wichtigste unabhängige Prognosefaktor für das Langzeitüberleben ist die vollständige Resektion aller Lungenmetastasen. Die Metastasenkonfiguration und das Metastasierungsmuster scheinen ebenso wie das krankheitsfreie Intervall, der Hormon- und HER2/neu-Rezeptorstatus für die Prognose zwar relevant, jedoch von nachrangiger Bedeutung zu sein. Intrapulmonale Metastasenrezidive können nach sorgfältiger Indikationsstellung ebenfalls reseziert werden. Dies kann in Einzelfällen ein günstiges Langzeitüberleben ermöglichen. Die Lungenmetastasenchirurgie sollte die Therapie der Wahl für selektionierte Patientinnen mit pulmonal metastasiertem Mammakarzinom sein.

Accurate pathologic nodal staging improves early stage non-small cell lung cancer survival. In an ongoing implementation study, we measured the impact of a surgical lymph node specimen collection kit and a more thorough pathologic gross dissection method on attainment of guideline-recommended pathologic nodal staging quality.We prospectively collected data on curative intent non-small cell lung cancer resections from 2009 to 2016 from 11 hospitals in four contiguous Dartmouth Hospital referral regions. We categorized patients into four groups based on exposure to the two interventions in our staggered implementation study design. We used χOf 2,469 patients, 1,615 (65%) received neither intervention; 167 (7%) received only the pathology intervention; 264 (11%) received only the surgery intervention; and 423 (17%) had both. Rates of nonexamination of lymph nodes reduced sequentially in the order of no intervention, novel dissection, kit, and combined interventions, including nonexamination of any lymph nodes and hilar/intrapulmonary and mediastinal nodes (p0.001 for all comparisons). The rates of attainment of National Comprehensive Cancer Network, Commission on Cancer, American Joint Committee on Cancer, and American College of Surgeons Oncology Group guidelines increased significantly in the same sequential order (p0.001 for all comparisons).The combined effect of two interventions to improve pathologic lymph node examination has a greater effect on attainment of a range of surgical quality criteria than either intervention alone.

We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.