Search

Die Pulmonale Lymphangioleiomyomatose (LAM) ist eine seltene Lungenerkrankung, die fast ausschlieslich bei Frauen auftritt. Insgesamt wird in Deutschland von 200–400 Erkrankten ausgegangen. Unterschieden werden eine sporadische und eine mit dem Tuberose-Sklerose-Komplex (TSC) assoziierte Form, denen Mutationen des TSC1- bzw. TSC2- Gens zugrunde liegen. Charakteristisch sind pulmonale Multizysten und randstandige mikronodale Proliferate aus LAM-Zellen. Typisch sind Kombinationen mit renalen Angiomyolipomen und beim TSC auch mit Gliomen, fazialen Angiofibromen und ungualen Fibromen. Die Prognose ist relativ gunstig (10-Jahres-Uberlebensrate: 80 %). Durch den Einsatz von mTORC1-Inhibitoren konnte diese deutlich verbessert werden. Im Einzelfall kommt eine Lungentransplantation in Betracht.

Purpose The aim of this study was to compare the pattern of intra-patient spread of lymph-node (LN)-metastases within the mediastinum as assessed by 18F-FDG PET/CT and systematic endobronchial ultrasound-guided transbronchial-needle aspiration (EBUS-TBNA) for precise target volume definition in stage III NSCLC. Methods This is a single-center study based on our preceding investigation, including all consecutive patients with initial diagnosis of stage IIIA-C NSCLC, receiving concurrent radiochemotherapy (12/2011–06/2018). Inclusion criteria were curative treatment intent, 18F-FDG PET/CT and EBUS-TBNA prior to start of treatment. The lymphatic drainage was classified into echelon-1 (ipsilateral hilum), echelon-2 (ipsilateral LN-stations 4 and 7) and echelon-3 (rest of the mediastinum, contralateral hilum). The pattern of spread was classified according to all permutations of echelon-1, echelon-2, and echelon-3 EBUS-TBNA findings. Results In total, 180 patients were enrolled. Various patterns of LN-spread could be identified. Skip lesions with an involved echelon distal from an uninvolved one were detected in less than 10% of patients by both EBUS-TBNA and PET. The pattern with largest asymmetry was detected in cases with EBUS-TBNA- or PET-positivity at all three echelons (p p p = 0.0021, Breslow-Day test), while PET did not (p = 0.19). Conclusion Frequent patterns of LN-metastatic spread could be defined by EBUS-TBNA and PET and discrepancies in the pattern were seen between both methods. EBUS-TBNA showed more lobe and tumor laterality specific patterns of LN-metastases than PET and skipped lymph node stations were rare. These systematic relations offer the opportunity to further refine multi-parameter risk of LN-involvement models for target volume delineation based on pattern of spread by EBUS-TBNA and PET.

Arteriosklerose fuhrt durch langsame Entwicklung von Stenosen oder durch plotzliche Okklusion des Gefaslumens durch einen Thrombus zu klinischer Symptomatik. Diese entsteht durch verminderte Perfusion im Myokard (koronare Herzerkrankung, KHK), im zentralen Nervensystem (Apoplexie) oder in den Extremitaten (periphere arterielle Verschlusskrankheit, pAVK). Die KHK stellt die haufigste Manifestation arteriosklerotischer Gefaslasionen dar und umfasst sowohl die stabile Angina pectoris wie auch die akuten Koronarsyndrome. Arteriosklerose ist eine im Wesentlichen durch Lipoproteinakkumulation in der Arterienwand ausgeloste Erkrankung, welche mit der Formation von Plaques an bestimmten Stellen des arteriellen Systems einhergeht. Die entscheidenden Pathomechanismen umfassen Entzundung, Nekrose, Fibrose und Kalzifizierung. Nach jahrzehntelangem indolenten Verlauf kann es plotzlich zu lebensbedrohlichen akuten Koronarsyndromen kommen. In den allermeisten Fallen ist die zugrunde liegende Lasion eine rupturierte Plaque, deren nekrotisches Material ihres „Kerns“ eine hohe Thrombogenitat aufweist. Die arteriosklerotischen Lasionen, die zu einer plotzlichen Thrombosierung mit kompletter oder inkompletter Okklusion fuhren konnen, sind das sog. „thin-cap fibroatheroma“, die Plaque-Erosion und das sog. kalzifizierte Knotchen bei stark verkalkten Arterien alterer Individuen, wobei der jeweilige Pathomechanismus bis dato nicht vollstandig geklart ist. Die vorliegende Ubersichtsarbeit soll einen Uberblick uber die Entstehung der wichtigsten arteriosklerotischen Veranderungen und deren Progression zur Plaque-Ruptur bzw. Thrombusformation geben.

Increasingly frequent, it is clinically indicated to obtain tissue from a peripheral lung lesion (PLL) to yield a pathological diagnosis. The aim of the present study was to evaluate the diagnostic sensitivity of transbronchial needle aspiration (TBNA) and transbronchial catheter aspiration (TBCA) in addition to transbronchial forceps biopsy (TBB) at conventional bronchoscopy. Eligible patients showing a PLL on computed tomography scans were included in the study. In all patients, following TBB, TBNA and TBCA were employed in randomised order under fluoroscopy. Fourty-eight patients were enrolled, of whom 46 patients with 46 PLLs were included in the analysis. The mean ± SD diameter of the PLL was 27.0 ± 13.3 mm. The overall sensitivity for all modalities was 69.6 %; PLL ≤20 or >20 and ≤30 mm in diameter showed a sensitivity of 60.0 and 72.2 %, respectively. For malignant PLL (n = 33), the combined sensitivity of TBNA + TBCA versus TBB was significantly higher (63.6 vs. 33.3 %, p ≤ 0.05), and could not further be improved by TBB. For benign PLL, TBB was superior to TBNA + TBCA (76.9 vs. 38.5 %). TBB, TBNA and TBCA are complementary to one another. Combining the three techniques, even allows transbronchial specimen collection of PLL

Charakteristika Die primare ziliare Dyskinesie (PCD) ist eine seltene angeborene Erkrankung der Zilien, die sich zumeist im respiratorischen System manifestiert.

Background:Tubulin-binding agents (TBAs) are effective in non-small cell lung cancer (NSCLC) treatment. Both ΒIII-and ΒV-tubulins are expressed by cancer cells and may lead to resistance against TBAs.Methods:Pre-treatment samples from 65 locally advanced or oligometastatic NSCLC patients, who underwent uniform induction chemotherapy with paclitaxel and platinum followed by radiochemotherapy with vinorelbine and platinum were retrospectively analysed by immunohistochemistry. Protein expression of ΒIII-and ΒV-tubulin was morphometrically quantified.Results:Median pre-treatment H-score for ΒIII-tubulin was 110 (range: 0-290), and 160 for ΒV-tubulin (range: 0-290). Low ΒIII-tubulin expression was associated with improved overall survival (OS) (P=0.0127, hazard ratio (HR): 0.328). An association between high ΒV-tubulin expression and prolonged progression-free survival (PFS, median 19.2 vs 9.4 months in high vs low expressors; P=0.0315, HR: 1.899) was found. Further, high ΒV-tubulin expression was associated with objective response (median H-score 172.5 for CR+PR vs 120 for SD+PD patients, P=0.0104) or disease control following induction chemotherapy (170 for CRPRSD vs 100 for PD patients, P=0.0081), but not radiochemotherapy.Conclusion:Expression of ΒV-tubulin was associated with treatment response and PFS following paclitaxel-based chemotherapy of locally advanced and oligometastatic NSCLC patients. Prolonged OS was associated with low levels of ΒIII-tubulin. Prospective evaluation of ΒIII/ΒV-tubulin expression in NSCLC is warranted. © 2012 Cancer Research UK.

Die endobronchiale ultraschallgestutzte Feinnadelaspiration (EBUS-TBNA) ist ein integrativer Bestandteil der Diagnostik und der Staging-Untersuchungen maligner Tumoren der Lunge und des Mediastinums. „Rapid on-site evaluation“ (ROSE) bezeichnet ein zytomorphologisches Schnellverfahren, das wahrend der laufenden bronchoskopischen Untersuchung durchgefuhrt werden kann und die sofortige („On-site“) Beurteilung von Materialmenge und -qualitat sowie uberwiegend auch bereits die Diagnose anhand einer Schnellfarbung innerhalb von Minuten ermoglicht. Dies reduziert die Anzahl benotigter Zweituntersuchungen aufgrund nicht geeigneten und/oder nicht ausreichenden Materials signifikant und vermindert so sowohl die Belastung der Patienten als auch die Kosten. Das gewonnene Material kann anschliesend weiter als konventionelle Zytologie, alternativ auch im Dunnschichtverfahren („thin-prep“) und/oder als Paraffinblock aufgearbeitet werden und fur weitere immunhistochemische und molekularbiologische Untersuchungen, wie z. B. Mutationsanalyse oder Durchflusszytometrie, herangezogen werden.

Die bronchoalveolare Lavage (BAL) bietet heute, neben einem hohen Sicherheitsprofil, eine Fulle von Befunden, die als diagnostische Marker eine Rolle spielen. Sie ist bei allen unklaren interstitiellen Lungenerkrankungen, auch bei solchen mit infektioser Genese, zur diagnostischen Standarduntersuchung geworden. Bei relativ spezifischen Befunden wie der pulmonalen Alveolarproteinose, Langerhans-Zell-Histiozytose, der diffusen alveolaren Blutung, diffusen malignen Infiltraten oder bei Staubexposition ist eine Lungenbiopsie meist nicht mehr erforderlich. Bei anderen Erkrankungen wie der Sarkoidose oder der exogen-allergischen Alveolitis kann bei entsprechender Klinik und radiologischem Befund das differenzialdiagnostische Spektrum stark eingeschrankt werden und auch in vielen Fallen die Diagnose ohne Biopsie gestellt werden. Bei der idiopathischen Lungenfibrose tragt die BAL zur Ausschlussdiagnostik, vor allem von Erkrankungen mit einer lymphozytaren BAL, bei.

Die primare ziliare Dyskinesie (PCD) ist eine klinisch und genetisch heterogene hereditare Erkrankung. Der Phanotyp der Erkrankung erklart sich durch angeborene Defekte respiratorischer Flimmerharchen (Zilien). Aufgrund einer verminderten mukoziliaren Reinigung der Atemwege kommt es zu rezidivierenden Infektionen der oberen und unteren Atemwege. Die Halfte der PCD-Patienten weist aufgrund einer zufalligen Anordnung der Links/Rechts-Korperasymmetrie einen Situs inversus (Kartagener Syndrom) auf. Bei klinischem Verdacht kann die Diagnose durch Elektronenmikroskopie, hochauflosende Immunfluoreszenzmikroskopie und/oder direktmikroskopische Evaluation des Zilienschlages bestatigt werden. Kurzlich konnten Mutationen bei rezessiv vererbter PCD mit auseren Dyneinarmdefekten in den Genen DNAI1, DNAH5, DNAH11, TXNDC3 nachgewiesen werden. Hierbei finden sich DNAH5-Mutationen in mehr als 50% der Falle. Selten finden sich Mutationen bei Jungen mit X-chromosomal rezessiver PCD, assoziiert mit Retinitis pigmentosa (RPGR) oder einem komplexen mentalen Retardierungssyndrom mit Makrozephalie (OFD1).

Human cytomegalovirus (HCMV) retinitis frequently occurs in severely naturally and iatrogenically immunocompromised patients. It has been shown that the immune-privileged retina is a major site of HCMV infection in AIDS patients. It is conceivable either that during the immunosuppression HCMV infection reactivates in various other organs viremically affecting the retina or that HCMV persisting in the retina may locally reactivate and result in HCMV retinitis. As there is still controversy about the sites of HCMV latency and persistence we investigated 75 eyes of HIV-seronegative patients undergoing enucleation due to a variety of malignant and non-viral benign ophthalmic disorders for the retinal presence of HCMV antigen and DNA. None of the analyzed patients had symptoms of HCMV retinitis. Immunohistologic staining as well as TaqMan DNA PCR analysis showed all samples to be free of HCMV. Our data suggest that the human eye is rather unlikely to be a site of productive or latent HCMV persistence.

We have used the minipig as a prospective animal model for human risk characterization to study primary biochemical alterations upon oral contaminant intake. The effects of three orally administered soils containing polycyclic aromatic hydrocarbons (PAH) on the expression pattern of the cytochrome P450 enzyme CYP1A1 in various organs have been analyzed. Dependent on the soil sample, subchronic daily oral PAH doses ranged from 0.38 to 1.90 mg PAH(EPA)/kg body weight. In all cases, soil administration lead to significant CYP1A1 induction in several organs of minipigs to a different extent, following the order liver approximately = duodenumlungkidney approximately = spleen. Hepatic ethoxyresorufin- O-deethylase activities were elevated to 310, 1250 and 1780 compared with a background level of 200 pmol resorufin/mg protein per min. Induced duodenal activities appear to be even higher than in the liver, namely 405, 1280 and 2500 compared with a basal activity of 11 pmol resorufin/mg protein per min. CYP1A1 induction in several organs is clear evidence for successful contaminant mobilization and absorption in the duodenum and subsequent distribution of contaminant into diverse body compartments. As is shown in one case, impairment of CYP1A1 induction in the liver and thus breakdown of its PAH-metabolizing activity appears to have no effect on induced CYP1A1 levels in other organs. It appears important with respect to risk assessment that induction of CYP1A1 is particularly sensitive in the duodenum of minipigs and is achieved with soil doses which are in the range of amounts ingested by playing children due to hand-to-mouth activities. Induced duodenal CYP1A1 activities obtained in minipigs by oral exposure to PAH largely exceed maximal duodenal activities so far observed in rats. This is equally relevant for risk assessment and for selection of a suitable animal model that reflects effects of PAH exposure in humans.

Chlamydia pneumoniae has been detected in atherosclerotic plaques by various means. Chlamydiae are able to cause persistent infections. Serologically elevated antibody titers are found in severe chronic obstructive pulmonary disease. In atherosclerosis and pulmonary emphysema, inflammatory reactions can be seen by means of light microscopy. Specimens from patients with obliterative arteriosclerosis undergoing thrombendarteriectomy and with advanced emphysema undergoing lung volume reduction surgery were examined using scanning (SEM) and transmission (TEM) electron microscopy, and using immunofluorescence with monoclonal antibodies and antiserum against chlamydiae. SEM shows spherical bodies (SBs) with a diameter from 0.3 µm to 0.6 µm on the surface of the alveoli and bronchioles, as well as in atherosclerotic plaques. In atherosclerosis and emphysema, SBs reveal a double membrane, adherence to collagen fibers, tissue destruction, as well as intracellular and interstitial localization in TEM. They show in parts a densely packed central structure. SBs are seen both in alpha-1-antitrypsin deficiency emphysema and smoker’s emphysema. Using immunofluorescence microscopy, spots are seen in corresponding distributions to the SBs. Morphological findings are typical for aberrant chlamydiae seen in persistent infections. Chronic infection and bacterial colonization associated with progressive disease seems to be relevant not only in atherosclerosis but also in pulmonary emphysema.

Chlamiophila pneumoniae were detected in targeted sections of mouse lung tissue by means of transmission electron microscopy and immunofluorescent staining. Incorporation of microorganisms into the axonemal matrix of cilia was observed 24 h after infection. The ciliary axoneme was characterized by pronounced swelling. At the late stages Chlamiophila pneumoniae were present in cytoplasmic vacuoles. Structural abnormalities and dysfunction of mucociliary clearance followed by incorporation of Chlamiophila pneumoniae into the cytoplasm of epitheliocytes were revealed in the early stage of infection. The proposed method allows studying the very early events of Chlamiophila pneumoniae infection.