Recent studies have shown that pulmonary neuroendocrine tumor (NET) subgroups, defined by the transcription factors OTP and ASCL1, correlate with age, sex, and tumor location. Their relationships with histology and hormone production, however, remain unclear. We analyzed 170 pulmonary NETs classified by OTP (O) and ASCL1 (A) expression into four groups: O + /A + , O + /A-, O-/A + , and O-/A-. Subgroups were assessed for histology, hormone expression, therapy-related markers, outcomes, and matched metastases. Among 152 resected primaries, O + /A + tumors (38%) were most frequent, occurring mainly in females (median age 72 years), and typically showed central or peripheral location, solid/spindle morphology with diffuse gastrin-releasing peptide (GRP), and focal ACTH/calcitonin. They also showed strong DLL3 expression and pronounced neuroendocrine cell hyperplasia. O + /A- tumors (23%) occurred predominantly in females (median age 56 years) with solid/trabecular patterns, occasional/ACTH, and strong SSTR2A/5 expression. O-/A- tumors (25%) were more common in males (median age 70 years), often central with solid/trabecular or oncocytic histology, serotonin expression (24%), and frequently SSTR2A-positivity. O-/A + tumors (14%) occurred across both sexes (median age 58 years), were centrally located, and solid, sometimes oncocytic features with moderate DLL3/SSTR2A expression. Metastases mirrored their primaries in transcription factor and hormone profiles. In the univariate analysis, OTP-negative tumors were associated with poorer disease-free survival (DFS). However, the multivariate analysis identified Ki67-based WHO grades (G1-G3) as the only independent prognostic factors. In conclusion, integrating OTP and ASCL1 refines pulmonary NET classification into four histologically and biologically distinct subgroups, providing additional insight into tumor heterogeneity. O + /A + tumors showed solid-spindle features and diffuse GRP and frequent ACTH expression, trabecular patterns characterized ASCL1-negative tumors, while oncocytic histology predominated in OTP-negative tumors, highlighting their role in defining tumor heterogeneity.

Abstract:The nationwide introduction of lung cancer screening using low-dose computed tomography (LDCT) is imminent in Germany. In contrast to other cancer screening programs, lung cancer screening follows a risk-based approach and specifically targets heavy current and former smokers aged 50 to 75 years. Following several years of pilot phases and regulatory preparation, the Federal Joint Committee (G-BA) decided in June 2025 to include this program as a regular benefit covered by statutory health insurance starting in 2026.Evidence from large international studies demonstrates a significant reduction in lung cancer mortality of approximately 20%. However, there are also risks such as overdiagnosis, unnecessary invasive procedures in false-positive findings, secondary cancers due to radiation exposure, and psychological burden.Key factors for program success include the structured involvement of qualified physicians in the identification, information, and assessment of eligibility of potential participants. Physicians in the fields of general medicine, occupational medicine, and internal medicine have been authorized after specific qualification, the latter of which includes pulmonologists - who, while not explicitly mentioned, will certainly have the closest contact with the high-risk population of smokers. This white paper provides practical information and materials for participating in lung cancer screening. It highlights the importance of dedicated interdisciplinary collaboration to detect as many lung cancer patients as possible at an early and therefore potentially curable stage.

We read with interest the study by Akil et al [...]

Malignant primary tracheal tumours are rare. The most common histological subtypes are squamous cell carcinoma and adenoid cystic carcinoma. These two entities have different prognoses and growth patterns. Tracheobronchoscopy and thoracic sectional imaging are standard diagnostic tools for tumour staging and local evaluation. Complete surgical resection of the affected tracheal segment is the treatment of choice for limited disease without distant metastases. Incomplete gross tumour resection with additional irradiation is an acceptable therapeutic option for adenoid cystic carcinoma. Interventional endoscopy with tumour debulking or tracheal stenting and/or definitive mediastinal radiotherapy are treatment alternatives in either a locally advanced or palliative setting.

Background/Objectives: Lung nodules present a common diagnostic challenge, particularly when benign and malignant lesions exhibit similar imaging characteristics. Standard evaluation relies on computed tomography (CT), positron emission tomography (PET), or biopsy, all of which have limitations. Quantitative magnetic resonance (MR) relaxometry using native longitudinal relaxation time (T1) and transverse relaxation time (T2) mapping offers a radiation-free alternative reflecting tissue-specific differences. Methods: This prospective, single-center study included 64 patients with 76 histologically or radiologically confirmed lung lesions (25 primary lung cancers, 28 metastases, 9 granulomas, and 14 pneumonic infiltrates). The patients underwent T1 and T2 mapping at 3T. Two independent readers quantified the mean values for each lesion. The pre-specified primary endpoints were (1) benign versus malignant and (2) primary lung cancer versus pulmonary metastases. Results: Significant differences in T1 and T2 values were observed across lesion types. Benign lesions exhibited high T2 values (mean 213.6 ms) and low T1 values (mean 836.6 ms), whereas malignant tumors exhibited lower T2 values (~77–78 ms) and higher T1 values (~1460–1504 ms, p < 0.001). Binary classification yielded 95.7% accuracy (sensitivity 93.8% for malignant, specificity 100% for benign) in an internal 70/30 hold-out validation (no external dataset), with consistent performance confirmed by patient-level and nested cross-validation (balanced accuracy ≈ 0.92–0.94). However, malignant subtypes could not be reliably distinguished (p > 0.05), and multiclass accuracy was 60.9%. Conclusions: Quantitative MR relaxometry allows accurate, radiation-free differentiation of benign and malignant lung lesions and may help reduce unnecessary invasive procedures.

The literature emphasizes that pulmonary ectopic Cushing syndrome (ECS) is associated not only with neuroendocrine tumors (NETs), but also with small cell lung carcinomas (SCLCs). This statement is debatable, because extrapulmonary ECS is associated with NETs in the vast majority of cases and very rarely with neuroendocrine carcinomas (NECs). Therefore, we critically reviewed the literature on SCLCs associated with ECS (ECS-SCLC) and performed immunohistochemical analysis of ACTH expression in 155 resected SCLCs and 158 pulmonary NETs. The literature search revealed that 90% of the 205 ECS-SCLC patients identified between 1952 and 2023 had no or poor-quality histologic images, so the diagnosis of SCLC could not be confirmed. Review of the 20 reports (10%) with histologic images revealed that 18/20 (90%) had to be reclassified as "probable NET", of which 5/18 (28%) showed spindle cell morphology, while only 2 cases were qualified as "SCLC compatible" due to their pleomorphic cell features. Immunohistochemically, 5/155 (3%) resected SCLCs, all without ECS, showed weak single cell ACTH expression, whereas in the NET cohort, 61/158 (39%) tumors expressed ACTH, of which 4 (3%) were associated with ECS. Both observations, the literature review, which casts doubt on previously reported data regarding the frequency of SCLC in ECS, and the immunohistochemical study, suggest that there is limited evidence that SCLC is the cause of ECS.

BACKGROUND:Pulmonary carcinoids are rare, low-grade malignant tumors characterized by neuroendocrine differentiation and relatively indolent clinical behavior. Most cases present as a slow-growing polypoidal mass in the major bronchi leading to hemoptysis and pulmonary infection due to blockage of the distal bronchi. Carcinoid syndrome is a paraneoplastic syndrome caused by the systemic release of vasoactive substances that presents in 5% of patients with neuroendocrine tumors. Due to such nonspecific presentation, most patients are misdiagnosed or diagnosed late and may receive several courses of antibiotics to treat recurrent pneumonia before the tumor is diagnosed. CASE SUMMARY:We report the case of a 48-year-old male who presented with cough, dyspnea, a history of recurrent pneumonitis, and therapy-refractory ulcerative colitis that completely subsided after the resection of a pulmonary carcinoid. CONCLUSION:We report and emphasize pulmonary carcinoid as a differential diagnosis in patients with nonresponding inflammatory bowel diseases and recurrent pneumonia.

To date, the factors which affect the age at diagnosis of lung adenocarcinoma are not fully understood. In our study, we examined the relationships of age at diagnosis with smoking, pathological stage, sex, and year of diagnosis in a discovery (n = 1694) and validation (n = 1384) series of lung adenocarcinoma patients who had undergone pulmonary resection at hospitals in the Milan area and at Thoraxklinik (Heidelberg), respectively. In the discovery series, younger age at diagnosis was associated with ever-smoker status (OR = 1.5, p = 0.0035) and advanced stage (taking stage I as reference: stage III OR = 1.4, p = 0.0067; stage IV OR = 1.7, p = 0.0080), whereas older age at diagnosis was associated with male sex (OR = 0.57, p < 0.001). Analysis in the validation series confirmed the ever versus never smokers' association (OR = 2.9, p < 0.001), the association with highest stages (stage III versus stage I OR = 1.4, p = 0.0066; stage IV versus stage I OR = 2.0, p = 0.0022), and the male versus female sex association (OR = 0.78, p = 0.032). These data suggest the role of smoking in affecting the natural history of the disease. Moreover, aggressive tumours seem to have shorter latency from initiation to clinical detection. Finally, younger age at diagnosis is associated with the female sex, suggesting that hormonal status of young women confers risk to develop lung adenocarcinoma. Overall, this study provided novel findings on the mechanisms underlying age at diagnosis of lung adenocarcinoma.

Die Kenntnis grundlegender Operationstechniken ist Voraussetzung für eine erfolgreiche thoraxchirurgische Behandlung. Anhand von Abbildungen werden praktische Schritte im Umgang mit dem Lungenparenchym, dem Tracheaobronchialsystem, den Lungengefäßen, der Thoraxwand sowie Pleura und Perikard erläutert.

Recent studies of severe acute inflammatory lung disease including COVID-19 identify macrophages to drive pulmonary hyperinflammation and long-term damage such as fibrosis. Here, we report on the development of a first-in-class, carbohydrate-coupled inhibitor of microRNA-21 (RCS-21), as a therapeutic means against pulmonary hyperinflammation and fibrosis. MicroRNA-21 is among the strongest upregulated microRNAs in human COVID-19 and in mice with acute inflammatory lung damage, and it is the strongest expressed microRNA in pulmonary macrophages. Chemical linkage of a microRNA-21 inhibitor to trimannose achieves rapid and specific delivery to macrophages upon inhalation in mice. RCS-21 reverses pathological activation of macrophages and prevents pulmonary dysfunction and fibrosis after acute lung damage in mice. In human lung tissue infected with SARS-CoV-2 ex vivo, RCS-21 effectively prevents the exaggerated inflammatory response. Our data imply trimannose-coupling for effective and selective delivery of inhaled oligonucleotides to pulmonary macrophages and report on a first mannose-coupled candidate therapeutic for COVID-19.

In diesem Kapitel werden die traditionellen Zugänge für offene Operationen beschrieben, ganz bewusst recht detailliert in einzelnen Schritten, da diese Zugänge im Zeitalter der minimalinvasiven Chirurgie schon fast in Vergessenheit geraten sind, in einer Notfallsituation jedoch – sicher beherrscht – lebensrettend sein können. Die operativen Zugänge für minimalinvasive videothorakoskopische Operationen (VATS) oder roboterassistierte Eingriffe werden in den jeweiligen Kapiteln dargestellt.

Chirurgische Erkrankungen der Trachea und/oder der Hauptbronchien sind im Kindesalter insgesamt sehr selten. Zu unterscheiden sind die angeborenen Fehlbildungen von den sekundär erworbenen und den Neoplasien. In den meisten Fällen handelt es sich um komplexe Krankheitsbilder, die das Leben der jungen Patienten deutlich einschränken oder gar akut gefährden.

Das vorliegende Kapitel beschreibt die Vorbereitung des Patienten im Operationssaal für einen thoraxchirurgischen Eingriff, angefangen von der Hautdesinfektion, der sterilen Abdeckung des Operationsgebietes und Lagerung des Patienten auf dem Operationstisch. Im Weiteren werden die verschiedenen Standard-Lagerungstechniken wie die Rückenlagerung, Seitenlagerung und Halbseitenlagerung detailliert beschrieben und mit Zeichnungen illustriert, sowie die typische Stellung der Operationsgruppe erläutert.

Krankhafte, nichtinfektiöse Veränderungen der Lunge im Kindesalter sind selten. Noch seltener besteht dabei die Notwendigkeit einer chirurgischen Intervention. Umso wichtiger ist es, die Diagnostik und Therapie in diesem Bereich weiterzuentwickeln. Manche Entitäten können dabei heute schon pränatal erkannt werden. Nach der Geburt sind die Symptome jedoch oft unspezifisch, was ein frühzeitiges Erkennen solcher Erkrankungen dann verzögert. Die Zuordnung gelingt nicht immer, selbst mit modernster Technik und aufwendigen Untersuchungen. Auch in der Therapie hat sich einiges getan. So hat die Thorakoskopie die offenen Verfahren in manchen Bereichen verdrängt. Die drei wichtigsten Bereiche für Lungenerkrankungen bei Kindern außerhalb der Infektionen, bei denen eine chirurgische Intervention notwendig werden kann, sind die angeborenen Fehlbildungen der Lunge, die Tumoren und in die Lunge metastasierte maligne Erkrankungen. Diese drei Bereiche werden im folgenden Kapitel näher betrachtet.

Since the reunification of the Federal Republic of Germany with the German Democratic Republic in 1990, Germany, situated in middle Europe, has become the most populous country in Europe with 83.5 million inhabitants. With a gross domestic product of 3.8 trillion U.S. dollars (2020), it is the largest national economy in the European Union and the fourth worldwide. As a result of the political reorganization after World War II, a federal organization has been adopted, delegating a large number of tasks to each of the 16 federal states, thereby, enabling a more regionalized approach (e.g., education or the health system).

Bei den meisten soliden Krebserkrankungen kommt der Operation im Rahmen der Behandlung eine zentrale Bedeutung zu. Studien zeigen teils deutliche Qualitätsunterschiede zwischen einzelnen Operateuren oder Versorgungsorganisationen. Wir beschreiben in dieser Arbeit eine Reihe von Herausforderungen bei der Messung von Versorgungsqualität in der (Onko‑)Chirurgie. Hierzu zählen beispielsweise die Komplexität der Intervention, die aufgrund des vergleichsweise geringen Studiengeschehens schwache Evidenz für die Formulierung von Prozessqualitätsindikatoren sowie das Erfordernis zur Case-Mix-Adjustierung, das eine umfassende Dokumentation erfordert. Wir stellen unter den zahlreichen existierenden Initiativen 3 Datenquellen und Programme vor, die derzeit Qualitätsvergleiche in der Onkochirurgie möglich machen: die Statistik der diagnosebezogenen Fallgruppen (DRG), die Qualitätssicherungsdaten zertifizierter Lungenkrebszentren und die PCO-Studie in Prostatakrebszentren. Aus Sicht der Autoren sollte künftig mehr in randomisierte kontrollierte Studien, in Qualitätsentwicklungsmaßnahmen wie das Lernen von „positiven Ausreißern“ und die Abbildung patientenberichteter funktionaler Outcomes in der Routine investiert werden.

Hintergrund: Die häufigste Komplikation nach Ventilimplantation zur endoskopischen Lungenvolumenreduktion (ELVR) ist ein postinterventioneller Pneumothorax (PTx), das Risiko liegt nach aktueller Datenlage zwischen 20 und 25%. Im Falle einer persistierenden Parenchymfistel muss bei manchen Patienten ein Ventil entfernt werden, um einen pleuralen Kontakt wiederherzustellen. Im Verlauf ist dann eine erneute Ventilimplantation möglich. Ziel der Analyse war es, das Risiko eines erneuten PTx zu evaluieren.