[Guideline (S2k, AWMF) of the Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin and the Deutsche Gesellschaft für Arbeitsmedizin und Umweltmedizin "Diagnostics and Expert Opinion in the Occupational Disease No. 4101 Silicosis (Including Coal Worker's Pneumoconiosis)"]. / S2k-Leitlinie nach AWMF-Schema der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin "Diagnostik und Begutachtung der Berufskrankheit Nr. 4101 Quarzstaublungenerkrankung (Silikose) der Berufskrankheitenverordnung".

During the last 1.5 years an update of the guideline on silicosis was made by an interdisciplinary working group. New medical and scientific knowledge and the experience in expert opinion practice were taken into account.By preparing the initial guideline in 2010 standardization of diagnostics and adaption of the "Moers convention" which was not based on medical knowledge was in the focus, whereas the current update deals with fine emendation and extension, especially of the compensation rate (adaption with the Reichenhall recommendation).The diagnosis of silicosis (including mixed dust pneumoconiosis) is based on a detailed occupational history, and predominantly on the typical radiological findings. However, at initial diagnosis the standardized LD-HRCT takes an important role because of its high sensitivity and specificity. Exceptional cases are those with characteristic findings in chest X-ray follow-up. Correspondingly, it is mentioned in the guideline: "The standardized appraisal of the Low-Dose-Volume HRCT requires application of the CT classification (ICOERD, International Classification of Occupational and Environmental Respiratory diseases). In order to diagnose silicosis in CT scan opacities with sharp borders in both central upper lung fields and their circumferencies have to be documented. By comparing with ILO standard radiographs at least profusion category 1 in the right and left upper lung fields has to be reached (total profusion category 2)."The pathologic minimal requirement for the diagnosis of silicosis which has undergone controversial discussion has now also been defined. Corresponding to Hnizdo et al. 2000 it is now mentioned: "Finding of less than 5 silicotic granuloma per lung lobe by palpation is regarded as insignificant." This is a convention and not a threshold based on detailed medical scientific and statistical studies; it is based on extended experience in the South African gold mines.This guideline also deals with silicotic hilar (and sometimes mediastinial) lymph nodes; according to the guideline working group they do not closely correlate with the degree of pulmonary involvement. Extended conglomerating and enduring lymph-node processes may lead to dislocation of the hili with impairment of large bronchi and vessels. Shell-like calcifications dominating in the periphery of lymph nodes produce so-called egg-shell hili.The paragraph on exercise testing is now extended: if neither ergometry nor spiroergometry can be performed a 6 minute walking test by measuring oxygen saturation should be done.Furthermore, in individual expert opinion examinations right heart catheterization (the patient is not obliged to give informed consent) may be recommended, if echo cardiography gives evidence for pulmonary hypertension or if it is difficult to differentiate between right and left heart failure. The presence of pulmonary hypertension which is of prognostic relevance has to be considered when grading reduction in earning capacity.For interpretation of spirometry values the new GLI reference values has to be applied. Grading of impairment is due to the recommendation of the DGP.According to current medical scientific knowledge it is unclear, whether certain disorders of the rheumatic group such is scleroderma or Caplan syndrome which are sometimes associated with silicosis (or coal workers' pneumoconiosis) belong in toto to the occupational disease number 4101 (silicosis). Within this context, additional studies are needed to clarify the role of occupational quartz exposure and other risk factors.The guideline working group hopes that this update will help to optimize diagnostics and expert opinion of silicotic patients.

Topographic deformation patterns of knee cartilage after exercises with high knee flexion: an in vivo 3D MRI study using voxel-based analysis at 3T.

OBJECTIVES: To implement a novel voxel-based technique to identify statistically significant local cartilage deformation and analyze in-vivo topographic knee cartilage deformation patterns using a voxel-based thickness map approach for high-flexion postures. METHODS: Sagittal 3T 3D-T1w-FLASH-WE-sequences of 10 healthy knees were acquired before and immediately after loading (kneeling/squatting/heel sitting/knee bends). After cartilage segmentation, 3D-reconstruction and 3D-registration, colour-coded deformation maps were generated by voxel-based subtraction of loaded from unloaded datasets to visualize cartilage thickness changes in all knee compartments. RESULTS: Compression areas were found bifocal at the peripheral medial/caudolateral patella, both posterior femoral condyles and both anterior/central tibiae. Local cartilage thickening were found adjacent to the compression areas. Significant local strain ranged from +13 to -15 %. Changes were most pronounced after squatting, least after knee bends. Shape and location of deformation areas varied slightly with the loading paradigm, but followed a similar pattern consistent between different individuals. CONCLUSIONS: Voxel-based deformation maps identify individual in-vivo load-specific and posture-associated strain distribution in the articular cartilage. The data facilitate understanding individual knee loading properties and contribute to improve biomechanical 3 models. They lay a base to investigate the relationship between cartilage degeneration patterns in common osteoarthritis and areas at risk of cartilage wear due to mechanical loading in work-related activities. KEY POINTS: • 3D MRI helps differentiate true knee-cartilage deformation from random measurement error • 3D MRI maps depict in vivo topographic distribution of cartilage deformation after loading • 3D MRI maps depict in vivo intensity of cartilage deformation after loading • Locating cartilage contact areas might aid differentiating common and work-related osteoarthritis.

[Recognize and classify pneumoconiosis]. / Pneumokoniosen erkennen und klassifizieren.

BACKGROUND: In the year 2012, out of the 10 most frequently recognized occupational diseases 6 were forms of pneumoconiosis. With respect to healthcare and economic aspects, silicosis and asbestos-associated diseases are of foremost importance. The latter are to be found everywhere and are not restricted to large industrial areas. PROBLEM: Radiology has a central role in the diagnosis and evaluation of occupational lung disorders. In cases of known exposure mainly to asbestos and quartz, the diagnosis of pneumoconiosis, with few exceptions will be established primarily by the radiological findings. As these disorders are asymptomatic for a long time they are quite often detected as incidental findings in examinations for other reasons. Therefore, radiologists have to be familiar with the pattern of findings of the most frequent forms of pneumoconiosis and the differential diagnoses. STANDARDIZED PROCEDURE IN EXAMINATIONS: For reasons of equal treatment of the insured a quality-based, standardized performance, documentation and evaluation of radiological examinations is required in preventive procedures and evaluations. Above all, a standardized low-dose protocol has to be used in computed tomography (CT) examinations, although individualized concerning the dose, in order to keep radiation exposure as low as possible for the patient. STANDARDIZED EVALUATION: The International Labour Office (ILO) classification for the coding of chest X-rays and the international classification of occupational and environmental respiratory diseases (ICOERD) classification used since 2004 for CT examinations meet the requirements of the insured and the occupational insurance associations as a means of reproducible and comparable data for decision-making.

[Update: standardized CT/HRCT classification of occupational and environmental thoracic diseases in Germany]. / Update: Standardisierte CT-/HRCT-Klassifikation der Bundesrepublik Deutschland für arbeits- und umweltbedingte Thoraxerkrankungen.

The high-resolution computed tomography (HRCT) coding scheme of the international classification of occupational and environmental respiratory diseases (ICOERD) presented here is an instrument for a standardized semiquantitative description of occupation and environment-linked as well as other pulmonary and pleural diseases. Analogous to the International Labour Organization (ILO) classification, the ICOERD coding scheme should always be used when the CT/HRCT examination is employed for occupational medical investigations or expert opinions. After publication of the guidelines and recommendations on diagnostics and expert assessment of asbestos-linked diseases and silicosis, the application of a standardized investigation program and assessment with the ICOERD classification form are obligatory, at least for the initial assessment. Furthermore, its use in the field of follow-up assessments of occupational diseases should be encouraged in order to guarantee comparability between individual reports (interreader variability) and at least a semiquantitative assessment of disease progression in isolated cases. Because the anatomical structures in projection radiography and CT are not presented identically, a 1:1 transfer of the results of the ILO classification to the CT/HRCT coding scheme is not possible. An overview image of the thorax does not allow overlap-free reproduction of structures, in contrast to CT. These methodological differences can in cases of isolated assessment result in different opinions of projection and CT images mostly by different investigators. In cases of discrepant opinions an integrated report of findings by combination of all information from both procedures is necessary.

[Asbestos-related diseases of the thorax]. / Asbestverursachte Veränderungen am Thorax.

Asbestos fibers can lead to pulmonary fibrosis, thickening of the pleura and malignancies. These pathologic changes are possible rather than determinate and depend on the type of asbestos fiber, length of exposure to fibers and individual factors. In Germany asbestos fibers were widely used until 1993. Worldwide, there is currently no general ban on the use of asbestos. The leading cause of asbestos-related diseases is occupational exposure. Due to a long latency period the appearance of such diseases may be delayed for more than 40 years so that the final number of cases has not yet been reached. Occupationally-derived asbestos-related diseases of the thorax are asbestosis, asbestos-related benign pleurisy and malignant pleural mesothelioma. Bronchial carcinoma can also be caused by asbestos exposure. For proof of occupational exposure, radiologists are required to report the presence of characteristic findings. The detection, in particular by chest X-ray and high resolution computed tomography (HRCT), requires high quality images and standardized evaluation. The standardized ILO classification and the semi-quantitative HRCT coding are medical findings on which statutory registration criteria are based.

[Examples for asbestos-related findings in HRCT - criteria for the assessment of causal relationships in surveillance programmes and medical expert opinion]. / Beispiele asbestfaserstaubbedingter Veränderungen im HRCT - Anhaltspunkte für die Kausalzuordnung bei Vorsorgeuntersuchungen und bei der gutachterlichen Beurteilung.

The increasing use of high-resolution computed tomography in formerly asbestos-exposed workers requires valid diagnostic criteria for the findings which have to be reported as suspicious for being asbestos-related in surveillance programmes and for the assessment of causal relationships between former asbestos exposure and findings in computed tomography. The present article gives examples for asbestos-related findings in HR-CT and discusses the specificity of parenchymal and pleural changes due to asbestos fibres.

[Recommendations for reporting benign asbestos-related findings in chest X-ray and CT to the accident insurances]. / Anzeigekriterien asbestfaserstaubbedingter Erkrankungen gemäss BK-Nr. 4103 BKV.

Asbestos-related diseases still play an important role in occupational medicine. The detection of benign asbestos-related diseases is one condition for the compensation of asbestos-related lung cancer in Germany. Due to the increasing use of computed tomography, asbestos-related diseases are more frequently detected in the early stages. The present article proposes recommendations for the findings which have to be reported as suspicious for being asbestos-related based on a) chest X-rays and b) computed tomography using the International Classification System for Occupational and Environmental Respiratory Diseases (ICOERD).

[Digital radiography in chest imaging of occupational and environmental lung diseases]. / Digitale Radiografie in der Untersuchung von arbeits- und umweltbedingten Lungen- und Pleuraerkrankungen.

The classification of pneumoconiosis according to ILO standard - comparing a X-ray of the lung with ILO radiographs - is well established in Germany. The extension of digital imaging is a challenging task in occupational medicine as well as in pneumology. Technical requirements are not known sufficiently and the necessary equipment is not well distributed. This paper describes the current position on recording, assessment and documentation of digital imaging of the lung and pleura.

Sub-acute occupational hypersensitivity pneumonitis due to low-level exposure to diisocyanates in a secretary.

There is virtually no information in the literature about the exposure levels needed to induce hypersensitivity pneumonitis (HP) by diisocyanates. The present study reports a case of occupational HP due to diisocyanates after low-level exposure. A 53-yr-old female never-smoker developed progressive shortness of breath on exertion, cough, fatigue and flu-like symptoms shortly after she began work as a secretary of a car body repair shop. A diagnosis of HP was made 2 yrs later, based on a restrictive ventilatory defect, a reticulonodular and discrete ground-glass pattern on high-resolution computed tomography, lymphocytosis in bronchoalveolar lavage and specific immunoglobulin G antibodies to diisocyanate human serum albumin conjugates in the patient's serum. The diagnosis was confirmed by recovery after exposure cessation and deterioration after re-exposure. Ambient monitoring revealed air concentrations of different diisocyanate monomers below the detection limit in both the patient's work station and in front of the paint spray booths, with the exception of one measurement that showed 4,4-methylenediphenyl diisocyanate concentrations of 3 microg x m(-3) in front of one booth (corresponding to a total reactive isocyanate group concentration of 1 microg x m(-3)). The present authors conclude that concentrations of diisocyanates far below current exposure limits may induce hypersensitivity pneumonitis in susceptible subjects.

Asbestos Surveillance Program Aachen (ASPA): initial results from baseline screening for lung cancer in asbestos-exposed high-risk individuals using low-dose multidetector-row CT.

The purpose of this study was to assess the prevalence of lung cancer in a high-risk asbestos-exposed cohort using low-dose MDCT. Of a population of 5,389 former power-plant workers, 316 were characterized as individuals at highest risk for lung cancer according to a lung-cancer risk model including age, asbestos exposure and smoking habits. Of these 316, 187 (mean age: 66.6 years) individuals were included in a prospective trial. Mean asbestos exposure time was 29.65 years and 89% were smokers. Screening was performed on a 16-slice MDCT (Siemens) with low-dose technique (10/20 mAs(eff.); 1 mm/0.5 mm increment). In addition to soft copy PACS reading analysis on a workstation with a dedicated lung analysis software (LungCARE; Siemens) was performed. One strongly suspicious mass and eight cases of histologically proven lung cancer were found plus 491 additional pulmonary nodules (average volume: 40.72 ml, average diameter 4.62 mm). Asbestos-related changes (pleural plaques, fibrosis) were visible in 80 individuals. Lung cancer screening in this high-risk cohort showed a prevalence of lung cancer of 4.28% (8/187) at baseline screening with an additional large number of indeterminate pulmonary nodules. Low-dose MDCT proved to be feasible in this highly selected population.

Selection of reference films based on reliability assessment of a classification of high-resolution computed tomography for pneumoconioses.

OBJECTIVE: Worldwide demand has increased for the development of a computed tomography (CT) classification system that supplements the ILO classification of radiographs for pneumoconioses. The authors aimed to show preliminary reliability test results for selected referent films for the CT classification system developed through an international effort by researchers from seven countries. METHODS: Reading trials by eight physicians who have considerable experience in pneumoconioses using a total of 114 lung zones consisting of 6 lung zones of 19 CT films of dust-exposed workers were performed to assess reliability of the classification system by weighted kappa. The results were also utilized for selecting reference films. RESULTS: A good agreement was observed for both first and second reading trials for rounded opacities (weighted kappa=0.76, 0.74, first and second trial results, respectively), irregular opacities (0.60, 0.48), emphysema (0.56, 0.70) and honeycombing (0.72, 0.79). Ground glass opacities, on the other hand, showed moderate agreement (0.43, 0.38). Intra-reader agreements among eight readers were shown in the same table as the mean and standard deviation of weighted kappa statistics. The inter-reader agreement for pleural thickening was not as good as for parenchymal lesions. DISCUSSION: The CT classification development may pioneer noble and sensitive medical screening for dust-exposed workers in selected settings. This system may be applied to radiographic borderline cases of profusion 0/1 and 1/0 by the ILO classification, in a setting that assures the occupational safety and health of workers exposed to some newly developed chemical compounds.

[Standardized CT/HRCT-classification of the German Federal Republic for work and environmental related thoracic diseases]. / Standardisierte CT/HRCT-Klassifikation der Bundesrepublik Deutschland für arbeits- und umweltbedingte Thoraxerkrankungen.

High resolution computed tomography (HRCT) plays an indispensable role in the diagnosis of pneumoconiosis and other lung damage arising from inhalation. Till now, however, there has been no agreed standardized convention for the use of the technique, or for documenting results uniformly. A task-group on Diagnostic Radiology in Occupational and Environmental Diseases of the German Radiological Society has produced a coding sheet based on experience gained in production of consultants' clinical reports, experts' examinations of patients seeking compensation for occupational lung disease, and physicians' professional development courses. The coding sheet has been used in a national multicenter study. It has been further developed and tested by an international working group comprising experts from Belgium (P.A. Gevenois), Germany (K.G. Hering, T. Kraus, S. Tuengerthal), Finland (L. Kivisaari, T. Vehmas), France (M. Letourneux), Great Britain (M.D. Crane), Japan (H. Arikawa, Y. Kusaka, N. Suganuma), and the USA (J. Parker). The intention is to standardize documentation of computertomographic findings in occupationally and environmentally related lung and pleural changes, and to facilitate international comparisons of results. Such comparisons were found to be achievable reproducibly with the help of CT/HRCT reference films. The classification scheme is purely descriptive (rather than diagnostic), so that all aspects of occupationally and environmentally related parenchymal and pleural abnormalities may be recorded. Although some of the descriptive terms used are associated with pneumoconiosis (e.g., rounded opacities in silicosis, or, in asbestosis, interlobular septal and intralobular non-septal lines, as well as honeycombing) many overlapping patterns that need to be considered for differential diagnosis are also included in the scheme.

[Further development of the International Pneumoconiosis Classification--from ILO 1980 to ILO 2000 and to ILO 2000/German Federal Republic version]. / Die Weiterentwicklung der Internationalen Staublungenklassifikation - von der ILO 1980 zur ILO 2000 und zur ILO 2000/Version Bundesrepublik Deutschland.

The ILO (1980) Classification has been revised during recent years. The new version is now available as the International Classification of Radiographs of Pneumoconioses (Revised edition 2000). The Guidelines booklet is currently available only in English. Those involved felt it was important to maintain continuity with the ILO (1980) edition, in particular to retain the standard radiographs, despite their restricted quality, so as to ensure comparability with earlier national and international data sets. The standard films illustrating pleural abnormalities, and 'u'-shadows, have been modified and reconstituted. The most important changes relate to assessment of film quality, pleural abnormalities, and additional symbols. In Germany, film quality is characterised as "+", "+-", "+--" and "u" according to whether the ability to assess pneumoconiosis is judged to be unimpeachable ("+") to unusable ("u"). If a film is not classified as "+", then written comments regarding defects are required. For "diffuse" pleural thickening, the ILO (2000) edition now requires the presence also of obliteration of the costophrenic angle. This was not required in the earlier (1980) edition and, as previously, is also not stipulated in the German version. A minimum width of 3 mm (previously 0-5 mm), coded "a", is required both for plaques as well as for the margin to the lateral chest wall. Congruence is thus achieved for criteria, which, in German practice, lead to an indication of suspect occupational disease. Plaques on the diaphragm are not considered for measurement of extent; they are only coded as present or absent. If calcification is identified, then this must also be classified and measured as a localised plaque. Extent of calcification on its own, previously coded "0" to "3", is no longer specified. The following new symbols, illustrated by new diagrams, have been introduced: aa = atherosclerotic aorta; at = apical thickening; cg = calcified granuloma (or other non-pneumocononiotic nodules); me = mesothelioma (already previously differentiated from "ca" on the German record sheet); pa = plate atelectasis; pb= parenchymal bands; ra = rounded atelectasis; od = other disease. (Examples of the latter are illustrated diagrammatically by lobar pneumonia, aspergilloma, goiter and hiatal hernia.) Earlier national differences (ILO 1980/German Federal Republic) on particular issues have also been agreed among German "double-readers" ["Zweitbeurteiler"]. However, conformity between the original (ILO 2000) text and the national (German) modified text has been retained in large measure. The detailed descriptions of the standard films differ in certain respects from the German (1980) definitions. Some revision of individual descriptions of the films are proposed. Except for a few differences, agreement was reached here too. The definitive date for the change in Germany is expected to be in early 2004. The standard films are already available now through ILO offices in Geneva or Bonn (addresses in appendix.)

Epirubicin and ifosfamide in metastatic breast cancer.

In a randomized, phase II trial, we evaluated the effectiveness of continued chemotherapy with epirubicin/ ifosfamide versus unmaintained treatment interruption in advanced metastatic breast cancer. Three hundred fifty-seven patients were enrolled and 331 were evaluable for response. Complete response was achieved in 25 patients (8%) and partial response in 121 patients (37%). Pretreatment status correlated significantly with response (complete and partial response). While 54% of unpretreated patients responded, only 42% of the patients responded who had been pretreated with adjuvant chemotherapy and 33% who had been pretreated in the metastatic stage of disease; 69 patients (21%) had disease progression. Of 11 patients pretreated in both the adjuvant and metastatic setting, only two responded. Toxicity of treatment was mild, with leukopenia being the treatment-limiting factor. Thrombocyte levels were not altered significantly by treatment. Thus, there seems to be room for dose escalation using granulocyte colony-stimulating factor. There was no considerable cardiotoxicity, central nervous system toxicity, or cystitis observed. The low rate of cardiotoxicity appeared to be related to dose fractionation of epirubicin. After randomization of patients to treatment interruption versus continuation of chemotherapy, a longer relapse-free survival was observed for patients who continued chemotherapy (mean relapse-free survival, 2+ months); however, this did not translate into prolonged survival. The cumulative scores of toxicity and quality of life parameters showed increasing superiority for treatment interruption. Therefore, a strategy of treatment until maximum response and subsequent treatment interruption seems to be superior to treatment continuation.