IntroductionWe present the case of a patient with recurrent bilateral hemothorax. After misdiagnosis despite several histological samples, a pleural manifestation of epithelioid angiosarcoma was diagnosed by further immunohistological staining. Based on this situation, we aim to sensitize the reader to this rare disease.Main concerns and important clinical findingsA 73-year-old fully conscious woman presented with dyspnea for 3 days. She was in stable general condition, pain was denied, she had a history of cigarette smoking, she had no cardiopulmonary events, and she was not receiving any anticoagulation medication. Physical examination revealed decreased breath sounds on the left side, and her hemoglobin level was 7.0 mmol/L.Primary diagnoses, interventions, and outcomesThe initial chest x-ray showed a left-sided effusion. Hemothorax was then diagnosed. Further investigation revealed no evidence of malignancy (CT, EBUS, cytology, etc.). VATS was performed, and biopsies of pleural lesions did not reveal congruent findings for the hemothorax. Due to recurrent bilateral hemothorax with the need for erythrocyte transfusion, the patient underwent several operations, including histological sampling, without evidence of malignancy. After further processing, an additional pathological report revealed an epithelioid angiosarcoma defined by massively proliferating epithelioid cells strongly positive for ERG and CD31 and negative for CD34. The neoplastic cells coexpressed D2-40 (podoplanin). Finally, due to multiple cerebral metastases, palliative therapy was indicated.ConclusionPhysicians and pathologists treating spontaneous hemothorax need to have broad knowledge of the possible, sometimes rare, etiologies. If the clinical course and intraoperative findings do not agree with the histopathological results, this finding must be questioned, and further immunohistochemical staining is mandatory. Thus, in the case of recurrent hemothorax, angiosarcoma of the pleura should also be considered for differential diagnosis.

OBJECTIVES:Solitary fibrous tumours of the pleura (SFTP) are historically considered to be benign soft tissue neoplasms. However, a clinical relevant number of these neoplasms have malignant histological features. The objective of this study was to evaluate the percentage of SFTP presenting unfavourable clinical behaviour in order to predict negative long-term outcome. METHODS:A retrospective review of 74 patients treated at 4 hospitals between 1990 and 2013 was performed. The median follow-up was 10 years (range: 1-20 years). Risk of tumour recurrence and metastases (unfavourable clinical behaviour) with regard to histology using the Kaplan-Meier and Cox proportional hazards methods. RESULTS:The mean age was 61 years (SD 12.75 years). There were 31 male patients (58%) and 43 female patients (42%). Tumour size ranged from 1 to 30 cm (mean 9.09 cm; SD 6.22 cm). Complete resection (R0) was achieved by minimally invasive thoracoscopic resection in 29% and thoracotomy in 57%; 25% of SFTPs showed histological evidence of malignancy, according to England criteria. Recurrence occurred in 21% and 10% of patients had metastases; 83% of patients with metastases and 39% of patients with recurrence died within 5 years. The median recurrence-free survival for histologically benign SFTP was not reached, compared to 8 years for malignant SFTP. The five-year overall survival rate was 84%. Mitotic rate ≥1/10 HPF, high cellularity, nuclear atypia, Ki-67 level >5% and poorly circumscribed (sessile) growth pattern were associated with poor long-term outcome. CONCLUSIONS:Pathological differentiation of SFTP morphology into pedunculated, well circumscribed and poorly circumscribed (sessile) growth pattern is recommended. Due to the misleading classification into histologically benign and malignant, all unpedunculated SFTP should be classified as potentially aggressive. Lifelong follow-up is mandatory.

Die neoadjuvante Immuntherapie bietet ein vielversprechendes Behandlungsverfahren des nichtkleinzelligen Lungenkarzinoms (NSCLC), dessen Prognose in der Vergangenheit trotz enormer Anstrengungen nicht wesentlich verbessert werden konnte. Nun geben (Immun‑)Checkpoint-Inhibitoren Anlass zur Hoffnung. Nun kam es 2022 zur ersten Zulassung durch die EMA, sodass einige Patientinnen und Patienten mit NSCLC bereits außerhalb klinischer Studien eine neoadjuvante Therapie im Kontext einer multimodalen Behandlung erhalten können. Die Ergebnisse anderer Studien werden mit Spannung erwartet. In der Zwischenzeit werden klinisch relevante Aspekte der Immuntherapie im klinischen Alltag immer präsenter. Nebenwirkungen der neoadjuvanten Therapie wie beispielswiese Pneumonie, Thyreoiditis oder Kolitis können zu einer Verzögerung der onkologischen Behandlung führen. Weiterhin bleibt die Indikationsstellung im Spannungsfeld zwischen kompletter pathologischer Remission und primärer Resistenz eine Herausforderung, mit der wir uns vermehrt auseinandersetzen werden müssen, und die uns Kenntnisse über Besonderheiten der neoadjuvanten Immuntherapie abverlangt. Die Lektüre dieser Publikation ermöglicht der chirurgisch tätigen Leserschaft ein über die unmittelbar perioperative Episode hinausreichendes klinisch relevantes Verständnis der Möglichkeiten und Grenzen der Immuntherapie des NSCLC.

Was ist neu? Früherkennung Risikopatienten zwischen 50 und 75 Jahren profitieren von einer jährlichen Low-Dose-CT-Untersuchung. Die Rahmenbedingungen werden aktuell erarbeitet. Inzidenteller Lungenrundherd Ein PET-positiver, malignitätsverdächtiger Lungenrundherd mit Größenprogredienz im zeitlichen Verlauf kann ohne histopathologische Sicherung bei Inoperabilität des Patienten stereotaktisch bestrahlt werden. Nicht kleinzelliges Lungenkarzinom (NSCLC) Es sollte bei allen Patienten mit NSCLC im Stadium IV eine Testung auf therapierbare Treiberalterationen erfolgen. Bei EGFR-Mutation (Exon 19 und 21) wird eine adjuvante Therapie mit Osimertinib über 3 Jahre empfohlen. Bei PD-L1-Expression ≥ 50% soll eine adjuvante Immuntherapie mit Atezolizumab im Anschluss an die adjuvante Chemotherapie erfolgen. Nach einer simultanen Radiochemotherapie im Stadium III soll bei PD-L1-Expression von ≥ 1% eine konsolidierende Immuntherapie mit Durvalumab über 1 Jahr erfolgen. Für viele Treiberalterationen stehen mittlerweile zielgerichtete Therapieoptionen zur Verfügung. Im Falle einer NTRK- oder RET-Fusion lautet die Empfehlung, die zielgerichtete Therapie in der Erstlinie durchzuführen. Im Falle einer MET-Exon-14-skipping-Mutation oder einer KRAS-G12C-Mutation ist eine Therapie ab der Zweitlinie sinnvoll und möglich. Kleinzelliges Lungenkarzinom – Behandlung des Stadiums M1 (Extensive disease) Es sollte allen Patienten mit metastasiertem kleinzelligem Lungenkarzinom eine kombinierte Immunchemotherapie angeboten werden. Grundsätze des Therapiemanagements Alle Patienten mit neu diagnostiziertem Lungenkarzinom sollten in einem interdisziplinären Tumorboard vorgestellt werden. Die in diesem Board beschlossenen Entscheidungen sollten sich an den aktuellen Leitlinien orientieren. Im Falle einer abweichenden Entscheidung muss diese gut begründet im Tumor-Konferenzprotokoll dokumentiert werden.

Lung carcinoma is still one of the most common forms of cancer in both sexes in Germany and the most common cause of cancer-related death. However, we are in the midst of a revolution in the treatment of lung cancer. Above all, the new immune and target therapies as well as the possible combinations of the individual therapy components have expanded the spectrum of drug therapy for lung cancer in recent years.Great progress has also been made in other fields. Be it in the context of early detection, where low-dose CT screening will soon be established for patients at risk, or in the context of molecular diagnostics with the identification of a large number of targets that can be specifically treated with tyrosine kinase inhibitors.Lung carcinoma therapy is moving on the direction of personalized tumor therapy that is specially tailored to each individual patient. Many studies on new drugs or new markers are ongoing. It is all the more important to keep track of the large number of newly approved substances and possibilities. Every patient should therefore, if possible, be treated in a lung cancer center with a therapy decision made in an interdisciplinary tumor board.The updated S3 guideline "Prevention, diagnostics, therapy and aftercare of lung cancer" was published in November 2022 as part of the guideline program oncology of the Working Group of Scientific Medical Societies, the German Cancer Society and the German Cancer Aid, financed by the German Cancer Aid. The full guideline is available at https://www.leitlinienprogramm-onkologie.de/leitlinien/lungenkrebs/ or in the guideline program app.There are already new treatment options that have not yet been taken into account in the recommendations. In order to take account of the dynamics of medical progress, the S3 guideline is going to be continued as a living guideline with annually updates.

ZusammenfassungDie aktuelle Fassung der Leitlinie Lungenkarzinom trägt der Dynamik der Informationen in diesem Fachbereich Rechnung. Insbesondere gelten folgenden Empfehlungen:Die Vorstellung aller neu diagnostizierten Patienten im interdisziplinären pneumoonkologischen Tumorboard ist verpflichtend, das CT-Screening für asymptomatische Risikopersonen (nach Zulassung durch die Behörden), Vorgehen beim inzidentellen Lungenrundherd (außerhalb von Screeningprogrammen), molekulare Testung aller NSCLC unabhängig vom Subtyp, in frühen Stadien auf EGFR-Mutationen und in der Rezidivsituation, adjuvante TKI-Therapie bei Vorliegen einer EGFR-Mutation, adjuvante Konsolidierung mit Checkpointinhibitor bei PD-L1 ≥ 50%, Erhebung des PD-L1-Status, nach Radiochemotherapie bei PD-L1-pos. Tumoren Konsolidierung mit Checkpointinhibitor, adjuvante Konsolidierung mit Checkpointinhibitor bei PD-L1 ≥ 50% im Stadium IIIA, Erweiterung des therapeutischen Spektrums bei PD-L1 ≥ 50%, unabhängig von PD-L1Status, neue zielgerichtete Therapieoptionen sowie die Einführung der Immunchemotherapie in der SCLC Erstlinie.Um eine zeitnahe Umsetzung künftiger Neuerungen zu gewährleisten, wurde die Umstellung auf eine „living guideline“ für das Lungenkarzinom befürwortet.

Hintergrund Trotz der breiten Anwendung der endobronchialen Lungenvolumenreduktion stellt die chirurgische Lungenvolumenreduktion weiterhin ein weltweit etabliertes Verfahren in der Therapie des schweren Lungenemphysems dar. Als Operationsprinzipien werden das Shaving oder die Lobektomie durchgeführt. Bisher gibt es nur wenige Studien die beide Verfahren direkt miteinander Vergleich. Eine Auswertung der Daten des Lungenemphysemregisters e.V. soll klären, ob ein Verfahren dem anderen überlegen ist.

The current S3 Lung Cancer Guidelines are edited with fundamental changes to the previous edition based on the dynamic influx of information to this field:The recommendations include de novo a mandatory case presentation for all patients with lung cancer in a multidisciplinary tumor board before initiation of treatment, furthermore CT-Screening for asymptomatic patients at risk (after federal approval), recommendations for incidental lung nodule management , molecular testing of all NSCLC independent of subtypes, EGFR-mutations in resectable early stage lung cancer in relapsed or recurrent disease, adjuvant TKI-therapy in the presence of common EGFR-mutations, adjuvant consolidation treatment with checkpoint inhibitors in resected lung cancer with PD-L1 ≥ 50%, obligatory evaluation of PD-L1-status, consolidation treatment with checkpoint inhibition after radiochemotherapy in patients with PD-L1-pos. tumor, adjuvant consolidation treatment with checkpoint inhibition in patients withPD-L1 ≥ 50% stage IIIA and treatment options in PD-L1 ≥ 50% tumors independent of PD-L1status and targeted therapy and treatment option immune chemotherapy in first line SCLC patients.Based on the current dynamic status of information in this field and the turnaround time required to implement new options, a transformation to a "living guideline" was proposed.

Pulmonary metastasectomy (PME) is one of the main therapeutic options with curative intent for selected patients with pulmonary metastases (PM) originating from various solid tumours, such as colorectal cancer (CRC) or renal cell carcinoma. PME is a widely performed operation and the theoretical concept of oligometastasis is also currently supported by gene expression analysis (1). Nevertheless, belief in its effectiveness is not universal as most data are primarily based upon registry data and surgical follow-up studies. Depending on the size and clinical focus of the particular department, lung metastasectomy can account for up to 25% of thoracic surgery procedures (2). In carefully selected patients resections can be associated with prolonged relapse-free survival and cure (3). Resection even in repeat settings or in cases of simultaneous liver and lung affection has become a widely accepted treatment for appropriately selected patients. Historically, Pastorino’s publication of the International Registry of Lung Metastases in 1997 established the foundation for lung metastasectomy in clinical practice (4). This review observed 5,206 patients with different primary metastatic tumours with PM The overall 5-, 10-, and 15-year survival rates were 36%, 26%, and 22%, respectively. Factors associated with a better prognosis were identified and included disease-free interval of 36 months and a single metastatic lesion. Basically, there is wide consensus on many aspects of PME as PM have to be completely resectable or the primary tumour is controlled or controllable. Other aspects remain contentious. In this regard, Prisciandaro’s findings in their current article are timely and relevant and provide a representative overview of the most important literature (5).

Background: Robust clinical evidence on the efficacy and safety of endoscopic lung volume reduction (ELVR) with one-way valves in patients with severe lung emphysema with chronic hypercapnic respiratory failure is lacking. Objective: The aim of this study was to compare patient characteristics, clinical outcome measures, and incidences of adverse events between patients with severe COPD undergoing ELVR with one-way valves and with either a partial pressure of carbon dioxide (pCO2) of ≤45 mm Hg or with pCO2 >45 mm Hg. Methods: This was a multicentre prospective study of patients with severe lung disease who were evaluated based on lung function, exercise capacity (6-min walk test [6-MWT]), and quality-of-life tests. Results: Patients with pCO2 ≤45 mm Hg (n = 157) and pCO2 >45 mm Hg (n = 40) showed similar baseline characteristics. Patients with pCO2 ≤45 mm Hg demonstrated a significant increase in forced expiratory volume in 1 s (p < 0.001), a significant decrease in residual volume (RV) (p < 0.001), and significant improvements in the quality of life and 6-MWT at the 3-month follow-up. Patients with pCO2 >45 mm Hg had significant improvements in RV only (p < 0.05). There was a significant decrease in pCO2 between baseline and follow-up in hypercapnic patients, relative to the decrease in patients with pCO2 ≤45 mm Hg (p = 0.008). Patients who were more hypercapnic at baseline showed a greater reduction in pCO2 after valve placement (r = −0.38, p < 0.001). Pneumothorax was the most common adverse event in both groups. Conclusions: ELVR with one-way valves seems clinically beneficial with a remarkably good safety profile for patients with chronic hypercapnic respiratory failure.

Intraoperative frozen sections of specimens taken during thoracic surgery are widely seen as the gold standard. However, the accuracy of intraoperative cytology remains contentious. The study aims to estimate the value of intraoperative cytology by analyzing feasibility, accuracy, time requirements, and possible limitations when compared to standard frozen sections. To this end, we examined a total of 532 intraoperatively harvested specimens out of the 518 resected thoracic tumors from 360 patients between August 2016 and August 2017. The specimens were subject to intraoperative rapid cytology that was later counter compared to the final histology results. The mean time between the intraoperative harvesting and arrival at the laboratory was 2.23 min, and it took a further 3.5 min until the results were communicated to the surgeon. Cytologically, 218 cases (41%) were classified as malignant, 291 (55%) as benign, and 23 (4%) remained unclear. In 55 malignant cases, we observed additional benign formations. The final histological examination performed later yielded 267 malignant and 265 benign cases. Therefore, the sensitivity and specificity of rapid intraoperative cytology were 82% and 99%, respectively, with a negative/positive predictive value of 86%/99%. We conclude that the intraoperative rapid cytology is a fast, accurate, sensitive, and specific procedure for intraoperative decision making and is a distinctly helpful alternative or adjunct for the thoracic surgeon, providing that one is aware of the plausible limitations of this technique.

Carcinoids are malignant neuroendocrine neoplasms showing good long-term survival after oncologic therapy. The study evaluated the influence of operative strategies and individual decision-making on the outcome and long-term survival in 222 patients with bronchial carcinoids. The patients underwent preoperative pulmonary function tests and bronchoscopy to facilitate surgical decision-making. A hundred and twelve tumors were detected endoscopically, including 32 in the main and lobar bronchi. We performed 5 isolated bronchus resections, 4 segmentectomies, 15 wedge resections, 10 pneumonectomies, 19 sleeve resections, 26 bilobectomies, 138 lobectomies, and 2 chest wall resections. Three patients were technically inoperable. Systematic mediastinal lymphadenectomy was routinely performed although most patients' computer tomography scans showed N0. A hundred and sixty-two patients had typical (155 N0, 7 N+) and 60 patients had atypical carcinoids (39 N0, 21 N+). There was no intraoperative mortality. The hospital mortality was below 2%. Overall, 1-, 5-, and 10-year survival rates were 99%, 94%, and 89%, respectively, in typical carcinoids. Atypical carcinoids show similar 1- and 5-year survival rates, but the 10-year survival rate was below 70%, decreasing in higher N-stages. The N-stage was the most important survival factor. In conclusion, bronchial carcinoids should be surgically treated the way lung cancer is. Anatomic resection and systematic lymphadenectomy are the treatments of choice. The availability of bronchoplastic techniques and preoperative assessment is essential for individual decision-making, focusing predominantly on postoperative quality of life.

Malignant mesotheliomas (MM) are rare tumors with high mortality rates, whose incidence varies regionally and nationally, and the diagnosis is difficult. Histology-based diagnosis is considered the gold standard despite its low sensitivity of 57-84%. However, recent advances in cytological analysis offer promise for diagnostic advancements. In this study, we reappraised the current cytological guidelines for the MM diagnosis and concluded on their practicability and reliability. The study included 5731 consecutive specimens of pleural effusions from 4552 patients (3026 males of the average age of 67.5 years and 1526 females of the average age of 65.4 years) between December 2017 and January 2000. Out of these patients, 444 (9.8%) were diagnosed with MM. The effusions were examined by immunocytochemistry using routine Giemsa staining. Additionally, hyaluronic acid (HA) was assessed. Cytological findings confirmed 223 out of the 444 MM. The additional 88 cases with negative cytology were corroborated by supplemental assessments of HA above 30 mg/L. Cytological evaluation accomplished the sensitivity of 0.50, specificity of 0.99, and a positive predictive value (PPV) of 0.97 for MM diagnosis. The use of HA determination raised the sensitivity to 0.70 without affecting the specificity or PPV. We conclude that cytological evaluation of effusions aided by the assessment of HA demonstrates the diagnostic sensitivity and specificity for MM no less than the hitherto standard histological evaluation. The cytology-based MM diagnosis may thus be routinely considered when MM is suspected and may offer confirmatory advantages in difficult or doubtful diagnostic cases.

ZusammenfassungDie frühe Letalität nach der Therapieeinleitung bei Patienten mit Lungenkarzinom im Stadium IV stand bisher selten im Fokus wissenschaftlicher Arbeiten. Die wenige verbleibende Zeit zwischen Diagnosestellung, Therapiebeginn und Todeseintritt sowie die evtl. beeinflussenden Faktoren beschäftigen jedoch Patienten und Behandler in hohem Maße. Entsprechend ist das Ziel dieser Arbeit die 30- und 90-Tage-Letalität nach Einleitung einer First-Line-Therapie zu analysieren und mögliche Einflussfaktoren auf eine frühe Letalität zu eruieren. Hierzu wurden retrospektiv die Daten von 225 Patienten mit Lungenkarzinom im Stadium IV und Behandlung im Lungenkrebszentrum Martha-Maria Halle-Dölau und in der Lungenklinik Ballenstedt im Zeitraum vom 01.01.2017 bis zum 18.05.2020 erfasst. Therapieformen und Patientenmerkmale wurden mittels Häufigkeitsverteilung analysiert und die Überlebenswahrscheinlichkeiten durch die Kaplan-Meier-Methode geschätzt. Die Analyse der frühen Letalität aller tumorspezifisch behandelten Patienten brachte zum Zeitpunkt 30 Tage nach Therapiebeginn eine Letalität von 8,5% und nach 90 Tagen eine Rate von 23,5%. Im direkten Vergleich der unterschiedlichen Therapiegruppen fielen die Patienten mit einer Monotherapie mit Checkpointinhibitoren mit einer höheren Letalität auf (16,6% nach 30 Tagen und 44,3% nach 90 Tagen). Hingegen blieb die Letalität der Patienten der anderen Therapiegruppen bei unter 10% nach 30 Tagen und unter 23,3% nach 90 Tagen. Als Prädiktoren für eine höhere frühe Letalität konnten ein schlechter Allgemeinzustand, eine fortgeschrittene Tumorerkrankung, eine Polymetastasierung sowie die positive Raucheranamnese eruiert werden. Dagegen bestand kein relevanter Unterschied der Letalität zwischen den unterschiedlichen Tumorentitäten, dem Geschlecht sowie dem PD-L1- und Mutationsstatus. Mit dieser Analyse konnte eine sehr hohe, mit anderen Untersuchungen vergleichbare frühe Letalität bei Patienten mit Lungenkarzinom nachgewiesen werden. Relevante Unterschiede zwischen den Therapieformen verdeutlichen die Wichtigkeit einer individuellen Patientenselektion zu den jeweiligen Therapieoptionen und die rasche Entscheidung zu einer Therapieeinleitung.

Introduction: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality rates. Endoscopic lung volume reduction with valves (ELVR-V) can produce favorable outcomes in patients with severe emphysema. In advanced stages, emphysema can eventually lead to chronic hypercapnic respiratory failure. Since ELVR-V targets hyperinflation and thereby reduces ventilatory workload, we hypothesized ELVR-V might be beneficial for patients with hypercapnia (PCO2>45mmHg). Methods: All data were derived from the LE-R, which is a national non-profit multicenter prospective study collecting data on patients with severe lung emphysema. PCO2 was assessed at baseline and 3-months follow up and a comparison between pre-and postprocedural outcomes was conducted. Results: In this study, 157 patients with a PCO2≤ 45 mmHg and 40 patients with a PCO2>45mmHg were included. Compared with baseline, ELVR-V in patients with a PCO2>45 mmHg led to a significant decrease of PCO2 (from 52.2± 6.2 mmHg to 43.7±8.6 mmHg; p=0.008) and of RV (from 271.9%±60.1 to 215.0 ±75.4; p=0.032) at 3 months follow up. Concerning unsolicited adverse events pneumothorax occurred commonly in both groups (PCO2≤45 mmHg: 17.2% vs. PCO2>45mmHg: 10.0%; p=0.862). Not a single death occurred in patients with hypercapnic failure. Table 1 depicts both groups regarding the clinical outcome after ELVR-V at 3-months follow up. Conclusions: We believe that ELVR with EBV should be considered in hyperinflated patients with chronic hypercapnia since it led to an improvement in lung function and to a significant decrease of PCO2.

Pulmonary metastasectomy is a well-established contribution to the cure of oligometastatic cancers, but its exact effectiveness is poorly understood. Here we report the outcomes of repeat pulmonary metastasectomy from a multicenter trial. This retrospective study included patients who underwent re-do metastasectomies between January 2010 and December 2014. The exclusion criterion was metastasectomy without curative intent. We reviewed medical files of 621 consecutive patients who underwent initial pulmonary metastasectomy. Of those, 64 patients underwent repeat metastasectomies, and these patients were included in the analysis. All the 64 patients underwent a second metastasectomy, later 35 of them underwent a third metastasectomy, 12 underwent a fourth metastasectomy, and 6 underwent a fifth metastasectomy. The total number of re-do metastasectomies was 181. The median overall survival among the patients undergoing re-do metastasectomy was 66.0 +/- 3.8 months. Three and 5-year survival rates were 82.3% and 63.3%, respectively. The 5-year survival rates were 63.3% after the first, 50.9% after the second, 74.4% after the third, 83.3% after the fourth, and 60.0% after the fifth metastasectomy. We conclude that at the current stage of knowledge, there is an indication for repeat re-do metastasectomy with curative intent.