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Purpose Preoperative pulmonary function testing is mandatory for non-small cell lung cancer (NSCLC) surgery. The predicted postoperative FEV1 (ppoFEV1) is used for further risk stratification. We compared the ppoFEV1 with the postoperative FEV1 (postFEV1) in order to improve the calculation of the ppoFEV1. Methods 87 patients voluntarily received an FEV1 assessment 1 year after surgery. ppoFEV1 was calculated according to the Brunelli calculation. Baseline characteristics and surgical procedure were compared in a uni- and multivariate analysis between different accuracy levels of the ppoFEV1. Parameters which remained significant in the multinominal regression analysis were evaluated for a modification of the ppoFEV1 calculation. Results Independent factors for a more inaccurate ppoFEV1 were preoperative active smoking (odds ratio (OR) 4.1, confidence interval (CI) 3.6–6.41; p = 0.01), packyears (OR 4.1, CI 3.6–6.41; p = 0.008), younger age (OR 1.1, CI 1.01–1.12; p = 0.03), and patients undergoing pneumectomy (OR 5.55, CI 1.35–23.6; p = 0.01). For the customized ppoFEV1 we excluded pneumonectomies. For patients $$1-\left(\frac{\text{Lung segments resected} + 1}{\text{Total number of segments}}\right)$$ 1 - Lung segments resected + 1 Total number of segments . For actively smoking patients with more than 30 packyears we subtracted one lung segment from the calculation ppoFEV1 = PreFEV1 × $$1-\left(\frac{\text{Lung segments resected} - 1}{\text{Total number of segments}}\right)$$ 1 - Lung segments resected - 1 Total number of segments . Conclusion We were able to enhance the predictability of the ppoFEV1 with modifications. The modified ppoFEV1 (1.828 l ± 0.479 l) closely approximates the postFEV1 of 1.823 l ± 0.476 l, (0.27%) while the original ppoFEV1 calculation is at 1.78 l ± 0.53 (2.19%). However, if patients require pneumectomy, more complex techniques to determine the ppoFEV1 should be included to stratify risk.

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.

OBJECTIVES Bovine and porcine pericardial patches are frequently used in cardiothoracic and vascular surgery. There are no guidelines recommending the usage of these patches for particular surgical approaches. However, these 2 materials supposedly possess different properties. The clinical advantage of porcine compared with bovine patches remains controversial. In this experimental study, we analysed the incorporation and vascularization of bovine and porcine pericardial patches during the initial phase after implantation. METHODS Bovine and porcine pericardial patches were implanted into the dorsal skinfold chamber of C57BL/6 mice (n = 8 per group) to study vascularization and inflammation at the implantation site using repetitive intravital fluorescence microscopy over a 14-day period. At the end of the in vivo experiments, CD-31-positive cells were determined to evaluate the vascularization by immunohistochemistry. Furthermore, cell proliferation and apoptosis were analysed immunohistochemically. RESULTS Implanted bovine patches exhibited an enhanced vascularization, as indicated by a significantly higher number of CD-31-positive cells and micro-vessels (23.2 ± 4.3 vs 16.5 ± 5.8 mm−2; P = 0.001). Furthermore, bovine patches showed a slightly but not significantly higher functional capillary density. Both patches induced a moderate leukocytic inflammatory host tissue response, and neither bovine nor porcine patches significantly affected apoptosis and cell proliferation at the implantation site. CONCLUSIONS Bovine and porcine pericardial patches are similarly suitable for surgery. Bovine patches exhibited an improved vascularization during the first 14 days after implantation. This may result in a quicker and improved incorporation into the surrounding tissue compared with porcine pericardial patches.

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

Adenocarcinoma (AC) is the number one pathological entity of lung cancer with approximately 30-40% of cases. It is known to be heterogeneous and has 5 histopathological growth patterns. We evaluated the long-term survival rates of patients with predominant subtypes.290 patients with AC underwent pulmonary resection between 2012 and 2017 at our institution. We excluded all patients with lymph node involvement and distant metastases. Hence, 163 patients were included for further analysis. Predominant growth pattern was defined if more than 10% of cells showed a growth pattern. 1, 3, and 5-year survival rates were evaluated. Survival was assessed by Kaplan-Meier curves and the Cox proportional hazards model was used to identify prognostic factors for overall survival.Predominant growth patterns10% were compared to10% growth patterns of the same subtype. 1-year, 3-year, and 5-year overall survival rates of patients with predominant solid tumor growth10% differed significantly from patients with10% (88.4% vs. 97.6%, p = 0.04; 65.8% vs. 87.4% p = 0.001, 36.4% vs. 65.9% p = 0.01). Survival rates did not differ between10% papillary and acinar growth compared to10%. Kaplan-Meier curves showed reduced overall survival for patients with solid tumor growth10% (log-rank 0.002). Solid tumor growth10% was an independent prognostic factor for worse long-term survival (Hazard ratio: 3.05, p = 0.01).Our study demonstrates that the presence of a predominant solid pattern in pulmonary adenocarcinoma is a factor for an unfavorable prognosis. This should be kept in mind in daily clinical practice.

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.

Background: The detection of PD-L1 in non-small cell lung cancer (NSCLC) is of great relevance for individualized therapy and has so far been performed using immunohistochemical analysis (IHC). With accompanying pleural effusion, the immunocytochemical analysis (ICC) could be of additive diagnostic value. Methods: 50 patients (17 women, 70±10 years, 26±5 kg/m²) with highly suspected NSCLC and pleural effusion were examined. PD-L1 expression of IHC and ICC samples were compared using the PD-L1 IHC 22C3 pharmDx Kit (Dako). Sensitivity and specificity of tumour and PD-L1 detection of ICC was determined with IHC as reference. PD-L1 was quantified according to percent of tumour cells expressing PD-L1. Due to different approval statuses of available immune checkpoint inhibitors, we considered different cut-offs for PD-L1 positivity. Results: Regarding the detection of malignancy, 7 cases with inconclusive ICC results were defined as tumour negative. Failed PD-L1 analyses were defined as PD-L1-negative. Conclusion: The detection of tumour cells in pleural punctate shows good sensitivity. PD-L1 detection is less sensitive but may still contribute to the identification of PD-L1-positive lung carcinoma. In case when invasive diagnostics (bronchoscopy, thoracoscopy) are not feasible, ICC of pleural punctate may offer a clinically valuable alternative to detect PD-L1-positive lung carcinoma with the option for 1st-line immune checkpoint inhibitor monotherapy.

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.

Sixty-one subjects with fibrosing interstitial lung disease were prospectively analysed to determine the efficacy of transbronchial cryobiopsy (CryoTBB) and the effect of procedural modifications which were introduced after an interim analysis of the first 19 subjects. The modifications significantly reduced complication rates from 84% to 14% (pNCT01714518.

Studienergebnisse der Vergangenheit stellen den therapeutischen Nutzen der Lungenmetastasenchirurgie fur Patienten mit pulmonal metastasiertem malignem Melanom infrage. Eine systematische Literaturrecherche und eine Analyse der Artikel, die ab dem 01.01.2000 veroffentlicht worden sind, sollen den Nutzen uberprufen und therapeutische Alternativen ermitteln. Nach der Metastasektomie erreichten die Patienten ein medianes Uberleben von 17 bis 40 Monaten und 5-Jahres-Uberlebensraten von 18–39,4%. Bis zu 30% der Patienten erlitten intrathorakale Rezidive, die in einigen Fallen durch Reoperationen erfolgreich therapiert worden sind. Verschiedene monoklonale Antikorper stehen als Behandlungsalternativen zur Verfugung und ermoglichen derzeit ein medianes Uberleben von bis zu 17 Monaten. Die Metastasektomie ist fur selektionierte Patienten die Therapie der Wahl, ihr Nutzen muss zukunftig jedoch im Vergleich zu den Pharmaka der aktuellen Generation erneut validiert werden.

BACKGROUND We hypothesized that the combination of a preoperative and a postoperative scoring system would improve the accuracy of mortality prediction and therefore combined the preoperative 'additive EuroSCORE' (European system for cardiac operative risk evaluation) with the postoperative 'additive CASUS' (Cardiac Surgery Score) to form the 'modified CASUS'. MATERIAL AND METHODS We included all consecutive adult patients after cardiac surgery during January 2007 and December 2010 in our prospective study. Our single-centre study was conducted in a German general referral university hospital. The original additive and the 'modified CASUS' were tested using calibration and discrimination statistics. We compared the area under the curve (AUC) of the receiver characteristic curves (ROC) by DeLong's method and calculated overall correct classification (OCC) values. RESULTS The mean age among the total of 5207 patients was 67.2 ± 10.9 years. Whilst the ICU mortality was 5.9% we observed a mean length of ICU stay of 4.6 ± 7.0 days. Both models demonstrated excellent discriminatory power (mean AUC of 'modified CASUS': ≥ 0.929; 'additive CASUS': ≥ 0.920), with no significant differences according to DeLong. Neither model showed a significant p-value (

Die Lungenmetastasenchirurgie ist ein etabliertes Verfahren in onkologischen Therapiekonzepten. Eine systematische Literaturrecherche und Analyse aller Studien, die ab dem 01.01.2000 publiziert worden sind, soll ihren Nutzen fur Patienten mit primaren Kopf-Hals-Tumoren (KHT) evaluieren. 1,9-13% aller Patienten mit KHT entwickeln Lungenmetastasen. Die Patienten erreichen nach der Metastasektomie 5-Jahres-Uberlebensraten bis zu 58 % und ein medianes Uberleben zwischen 9,5 und 78 Monaten. Die Raten fur intrathorakale Rezidive betragen 18,4–81,8 %. Diese Patienten konnen sich im Einzelfall einer Remetastasektomie unterziehen. Patienten mit Plattenepithelkarzinomen haben die ungunstigste Prognose, konnen aber ein Langzeituberleben (≥ 60 Monate) erreichen. Die Lungenmetastasenchirurgie stellt haufig den einzigen potenziell kurativen Ansatz dar und ermoglicht ein gunstigeres Langzeituberleben als nichtchirurgische Therapieformen. Sie sollte daher die Therapie der ersten Wahl fur diese Patienten sein.

Background: Prolonged intensive care unit (ICU) stay is a predictor of mortality. The length of ICU stay has never been considered as a variable in an additive scoring system. How could this variable be integrated into a scoring system? Does this integration improve mortality prediction? Material/Methods: The 'modified CArdiac SUrgery Score' (CASUS) was generated by implementing the length of stay as a new variable to the 'additive CASUS'. The 'logistic CASUS' already considers this variable. We defined outcome as ICU mortality and statistically compared the three CASUS models. Discrimination, comparison of receiver operating characteristic curves (DeLong's method), and calibration (observed/expected ratio) were analyzed on days 1-13. Results: Between 2007 and 2010, we included 5207 cardiac surgery patients in this prospective study. The mean age was 67.2 +/- 10.9 years. The mean length of ICU stay was 4.6 +/- 7.0 days and ICU mortality was 5.9%. All scores had good discrimination, with a mean area under the curve of 0.883 for the additive and modified, and 0.895 for the 'logistic CASUS'. DeLong analysis showed superiority in favor of the logistic model as from day 5. The calibration of the logistic model was good. We identified overestimation (days 1-5) and accurate (days 6-9) calibration for the additive and 'modified CASUS'. The 'modified CASUS' remained accurate but the 'additive CASUS' tended to underestimate the risk of mortality (days 10-13). Conclusions: The integration of length of ICU stay as a variable improves mortality prediction significantly. An 'ICU-day' variable should be included into a logistic but not an additive model.

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.