[Implementation of the German Guideline for the Prevention, Diagnosis, Treatment, and Follow-up of Lung Cancer in the Federal State of Berlin]. / Umsetzung der S3-Leitlinie zur Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms im Land Berlin.

BACKGROUND: In February 2010, the German guideline for the Prevention, Diagnosis and Treatment of Lung Cancer has been published. For the first time in Germany, the implementation of relevant guideline recommendations has been assessed in the federal state of Berlin. METHODS: Based on the quality indicators of the guideline, a questionnaire was designed which aimed at the application of selected diagnostic and therapeutic concepts. This questionnaire was sent out to all outpatient and inpatient units in the federal state of Berlin being presumably involved in lung cancer care. RESULTS: Overall response rate was good (39.8 %), especially from the addressed inpatient units. Inpatient pneumology units showed the highest application rates of guideline recommendations, followed by oncology units. CONCLUSIONS: Taking the methodologically reduced significance of a survey design into account, this study determined a negative trend of decreasing guideline implementation in units with a lesser grade of specialisation in terms of lung cancer care.

[Lung cancer - historical development, current status, future prospects]. / Lungenkrebs - Geschichtliche Entwicklung, derzeitiger Stand und Ausblick.

One hundred years ago lung cancer was a rare disease. In the meantime, as a result of the sharp increase of tobacco smoking, in Germany and worldwide it is the most common cause of cancer death. Since lung cancer is largely asymptomatic in its early stages, the diagnosis is usually first made in the advanced stages IIIB or IV. The development of diagnostic imaging and minimally invasive procedures as well as the refinement of the staging classification allow a better allocation to the tumor stages. The surgical mortality has declined significantly since the 1950s, yet the 5-year survival rates are low. For locally advanced, unresectable non-small cell lung carcinoma a moderate improvement of the prognosis could be achieved by newer methods of radiotherapy and the combination of radiotherapy with chemotherapy. As a result of chemotherapy in patients with non-small cell lung cancer a moderate life extension has been reached, while the new agents are better tolerated and allow for an improved quality of life. The survival of small cell lung cancer has been significantly prolonged by chemotherapy since the 1970s, however, little progress was made in the last 15 - 20 years. The most important and effective preventive measure against lung cancer is to avoid tobacco smoke. Screening tests using annual chest X-ray images and sputum cytology have shown no improvement in overall mortality compared with the control groups in extensive studies. Whether or not an improvement of prognosis is possible by a screening using low-dose CT is being tested by the ongoing studies. For patients with lung cancer more effective agents and therapies are still needed.

[Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)]. / Respiratorische Bronchiolitis mit interstitieller Lungenerkrankung (RB-ILD).

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) designates interstitial lung changes in smokers, characterized histologically by bronchiolocentric accumulation of pigmented alveolar macrophages and fibrotic or cellular inflammatory changes of pulmonary interstitium. The definition is nearly identical to that of condensate pneumopathy, smoker's pneumopathy or smoker's lung, defined by accumulation of pigmented alveolar macrophages with bland alveoloseptal or peribronchial fibrosis and cellular inflammation of the bronchial wall. In addition to respiratory bronchiolitis, which is found in nearly all smokers, RB-ILD comprises a broad spectrum of varying degrees of the interstitial reaction to the exogenous injury of inhalation smoking with gradual transition to desquamative interstitial pneumonia (DIP). In most cases RB-ILD manifestations are subclinical and detected coincidentally. Radiographic features are reticulonodular and ground glass opacities of the lung. The high resolution computed tomography reveals centrilobular nodules, ground glass opacities, thickening of bronchial walls, and in some cases a reticular pattern. Mild emphysema is frequent. Lung function analysis reveals only minor restrictive or obstructive defects in most cases, often combined with hyperinflation. CO diffusing capacity is slightly to moderately impaired. Pronounced interstitial lung diseases with serious restrictive defects and arterial hypoxemia have been reported infrequently. In differential diagnosis smoking related interstitial lung diseases (DIP, Langerhans cell histiocytosis, idiopathic pulmonary fibrosis) and other interstitial lung diseases have to be excluded. In most cases diagnosis can be achieved by bronchoalveolar lavage and transbronchial lung biopsy. In cases of pronounced interstitial lung disease or assumption of an additional interstitial lung disease besides RB-ILD a thoracoscopic or open lung biopsy can be necessary. RB-ILD has a favourable prognosis. After smoking cessation lung changes are reversible. Corticosteroid therapy is not necessary. A fatal outcome of RB-ILD has not been reported. Follow-up examinations are advisable in order to preclude other interstitial lung diseases. RB-ILD seems to be more frequent than it is assumed at present. The clinical picture is masked in most cases by the concomitant smoking induced chronic bronchitis. Thus only pronounced cases with structural changes and resulting differential diagnostic problems are diagnosed.

Tracheobronchial stenosis in Keutel syndrome.

In 1971 Keutel et al. described a new syndrome in two siblings presenting with peripheral pulmonary stenoses, brachytelephalangism, neural hearing loss and abnormal cartilage calcification. Recent investigations provided evidence that mutations in the gene encoding the human matrix GLA protein cause Keutel syndrome. With these new insights in the disease the symptomatology of Keutel syndrome was reassessed. The follow-up of the two siblings was studied by clinical and post mortem examination. As a new feature of Keutel syndrome tracheobronchial stenosis and concentric calcification of pulmonary, coronary, hepatic, renal, meningeal and cerebral arteries were described. Complementary to the results in molecular genetics the symptomatology of Keutel syndrome could be revised by clinical and post mortem examination.

Expression of p16 and lack of pRB in primary small cell lung cancer.

The retinoblastoma protein (pRB), p16, and cyclin D1 are major components of the RB pathway, which controls the G1 checkpoint of the cell cycle. Proper regulation of this pathway is crucial for normal cell proliferation. Abnormal forms of these proteins have been found in various types of malignant tumours. In the present report, immunohistochemical techniques were applied to study the expression of pRB, p16, and cyclin D1 in 161 samples of primary small cell lung cancer (SCLC) and 20 samples of non-small cell lung cancer (NSCLC). While pRB and cyclin D1 staining was negative in 161 specimens of SCLC, expression of p16 was observed in 153 samples. In contrast to SCLC, 16 out of 20 NSCLC cases exhibited pRB expression and 15 showed cyclin D1 expression, but only very weak p16 staining was found in five samples. These observations could provide additional criteria for the distinction between SCLC and NSCLC. Furthermore, these findings, based on primary tissues, implicate different mechanisms in the tumourigenesis of SCLC and NSCLC.

[Evolutionary quality assurance. A new concept for improving process and outcome quality]. / Evolutionäre Qualitätssicherung. Ein neues Konzept zur Verbesserung der Prozess-und Ergebnisqualität.

BACKGROUND: The concept evolutionary quality assurance is a new, non-mandatory, open peer review process for in-patients settings. METHOD: Ten medical charts (with radiographs) from participating hospitals were randomly chosen and assessed using a prespecified questionnaire (total 134). Individual inadequacies had to be justified on a case by case level. Reviewer and reviewee are known by names, allowing subsequent discussions on content between reviewer and reviewee prior to a final judgement. The final analysis was performed anonymously and communicated to the participants after completion of the process. Patients had to give their consent to the review process. The report, however, is not part of the medical patient file, so that access is not warranted. For the first cycle, all lung clinics and departments throughout Germany were asked to participate. 35 chest hospital (approximately 50%) agreed to participate. RESULTS: Data analysis revealed that almost all detected inadequacies were apparent, i.e. discussions on the discordant interpretation of diagnostic and therapeutic strategies rarely occurred (0.25%). Final analysis of the evaluation performance of reviewers judged less than 5% and 14% judged more than 30% of all quality inadequacies. CONCLUSIONS: The quality assurance process is comparably cheap and can be implemented without delay, because standards for reference values are not required. The structure allows adaptation in all areas of clinical medicine.

Cellular autofluorescent pigment and interstitial fibrosis in smoker's lung.

The mechanisms by which cigarette smoking lead to bronchopulmonary diseases are incompletely understood. The most characteristic lesion is a chronic macrophage-alveolitis accompanied by slight fibrosis and emphysema. The macrophages contain a ceroid-like granular autofluorescent pigment in their lysosomes. Using immunohistochemical methods, open lung-, transbronchial biopsies and cells obtained by broncho-alveolar lavage from cigarette smokers were studied: anti-human macrophage serum and anti-human elastase, immune sera against type I, type III collagens and fibronectin were used in the demonstration of the cellular components of alveolitis and the connective tissue constituents of fibrosis. The characteristic red-brown autofluorescent pigment of the macrophages was also found in an extra-alveolar location mainly in peribronchial, septal and pleural scars. Similar emission colour occurred focally in the elastic laminae of fibrotic alveoli and sclerotic arteries. Granular fluorescent pigment was found in many bronchial epithelial cells. The epithelial pigmentation was associated with increased transcription of nucleic acid proteins, revealed by colloid silver (AgNOR) reaction. The results suggest that the autofluorescent pigment substances in macrophages may indicate or also play a role in the development of pathological connective tissue and epithelial changes of smoker's lung, in addition to the known mediators and enzymes.

Lung function disturbances versus respiratory muscle fatigue in patients with systemic lupus erythematosus.

In 23 consecutive patients (mean age, 38.6 years) with systemic lupus erythematosus (SLE) and in 17 healthy subjects (mean age, 37.5 years) fatigue of respiratory (diaphragm, musculi intercostales externi) and leg muscles (musculus gastrocnemius) was determined comparatively by electromyography. Additionally, routine lung function parameters, including maximum inspiratory (PImax) and expiratory (PEmax) mouth pressures, were measured. The SLE patients showed lower values of vital capacity (VC), total lung capacity (TLC), thoracic gas volume (TGV), FEV1, PImax and PEmax than the healthy controls, while FEV1/VC, residual volume and specific airway conductance were not significantly different in either group. Lung compliance, corrected for TGV, was normal in the SLE group. Breathing through stenoses with increasing resistances resulted in fatigue of the diaphragm in 73% of the SLE group and in 41% of the control group. The corresponding values of the external intercostal muscles were 74% (SLE group) and 29% (control group). Electromyographic signs of respiratory and leg muscle fatigue occurred at lower loads in the SLE group than in the healthy subjects. The pattern of lung function data in patients with SLE was characteristic neither of lung restriction nor of airway obstruction. Respiratory muscle weakness can explain the decrease in TLC, VC, TGV, FEV1, PImax and PEmax.

[Cimetidine and ranitidine in intensive care patients. Double-blind randomized cross-over study on intravenous administration: hemodynamics, plasma coagulation, blood gases and acid-base status]. / Cimetidin und Ranitidin bei Intensivpatienten. Doppelblinde randomisierte Cross-over-Studie zur intravenösen Gabe: Hämodynamik, plasmatische Gerinnung, Blutgase und Säure-Basen-Status.

Intravenous cimetidine 200 mg, and ranitidine 50 mg were administered as 2 minute infusions to 50 intensive-care patients. Cimetidine and ranitidine differed significantly in their effect on systolic arterial blood pressure measured during the second minute (alpha = 0.01). In the case of cimetidine the haemodynamic parameters measured over 10 minutes revealed a clearly defined fall in systolic, diastolic and mean arterial blood pressure as well as a rise in heart rate. The initial values were regained 5 minutes after drug application. Adverse effects of ranitidine on haemodynamics were much less than those of cimetidine. Neither drug produced any essential change in clotting parameters (partial thromboplastin time, plasma thrombin time, thromboplastin time and fibrinogen) measured before and 5 minutes after application, nor had they any effect on blood-gases or acid-base status.