Single nucleotide polymorphisms in matrix metalloproteinase genes and lung cancer chemotherapy response and prognosis.

The prognosis for lung cancer patients treated with chemotherapy is poor. Single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMP) genes could influence treatment outcome by altering apoptotic pathways. Eight SNPs with known or suspected phenotypic effect in six genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) were investigated. For 349 Caucasian patients with primary lung cancer, receiving first-line chemotherapy, three different endpoints were analysed: response after the second cycle, progression free survival (PFS) and overall survival (OS). The prognostic value of the SNPs was analysed using multiple logistic regression for all patients and histology-, stage- and treatment-specific subgroups. Hazard ratio estimates for PFS and OS were calculated using Cox regression methods. None of the investigated polymorphisms modified response significantly in the whole patient population. However, tumour stage IIIB variant allele carriers of MMP2 C-735T showed a significantly worse response. PFS was significantly prolonged in MMP1 G-1607GG variant allele carriers and OS in small cell lung cancer patients carrying the MMP12 A-82G variant allele. In conclusion, this study identified SNPs in MMP1, MMP2, MMP7 and MMP12 for further investigation as possible predictors of chemotherapy outcome in lung cancer patients.

[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.

[The radiology of opportunistic pneumonias. I: Epidemiological, laboratory and clinical background]. / Radiologie der opportunistischen Pneumonien. Teil I: Epidemiologie, laborchemische und klinische Grundlagen.

In the guidelines of the German Society of Pneumology on diagnosis and therapy of opportunistic pneumonias, chest x-ray is listed as the basic diagnostic method in congenital and acquired immunodepression. In case of discrepancy between radiographic and the clinical findings or in cases of bilateral infiltrates, infection refractory to therapy or a difficult course in patients requiring artificial ventilation, a CT, or if necessary, ultrasound or MRI should be carried out. Cross-sectional imaging allows more precise assessment of the radiological pattern, estimation of the degree of severity (number of infiltrated segments) and detection of complications (pleural effusion, empyema, thorax wall infiltration). Clinical and laboratory parameters, bacteriological and serological examinations as well as information on the underlying immunocompromising factors must be taken into account in the differential diagnosis. The radiographic finding is an important diagnostic parameter which is used in the determination of the degree of severity of the pneumonia. The pattern of findings is one of rationales for the use of antibiotic therapy. In the first part of this contribution the epidemiological, laboratory and clinical background of the diagnosis of opportunistic pneumonias is discussed.

[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.

Perfusion CT in patients with advanced bronchial carcinomas: a novel chance for characterization and treatment monitoring?

Advanced bronchial carcinomas by means of perfusion and peak enhancement using dynamic contrast-enhanced multislice CT are characterized. Twenty-four patients with advanced bronchial carcinoma were examined. During breathhold, after injection of a contrast-medium (CM), 25 scans were performed (1 scan/s) at a fixed table position. Density-time curves were evaluated from regions of interest of the whole tumor and high- and low-enhancing tumor areas. Perfusion and peak enhancement were calculated using the maximum-slope method of Miles and compared with size, localization (central or peripheral) and histology. Perfusion of large tumors (> 50 cm3) averaged over both the whole tumor (P = 0.001) and the highest enhancing area (P = 0.003) was significantly lower than that of smaller ones. Independent of size, central carcinomas had a significantly (P = 0.04) lower perfusion (mean 27.9 ml/min/100 g) than peripheral ones (mean 66.5 ml/min/100 g). In contrast, peak enhancement of central and peripheral carcinomas was not significantly different. Between non-small-cell lung cancers and small-cell lung cancers, no significant differences were observed in both parameters. In seven tumors, density increase after CM administration started earlier than in the aorta, indicating considerable blood supply from pulmonary vessels. Tumor perfusion was dependent on tumor size and localization, but not on histology. Furthermore, perfusion CT disclosed blood supply from both pulmonary and/or bronchial vessels in some tumors.

[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.)

Near-fatal hemoptysis and emergency surgical repair after aortic patch-plasty.

A 38-year-old man presented with massive hemoptysis followed by hemorrhage shock. The patient's history revealed a Dacron patch repair for aortic coarctation and recoarctation carried out twice, once 23 and once 10 years ago. Diagnosis of a ruptured descending aortic aneurysm with an aortobronchial fistula into the left lower lobe was established using CT scan. Emergency surgery consisted of left pneumonectomy and descending aortic graft replacement during deep hypothermic circulatory arrest. The patient was discharged 12 days later.

[MRT, CT and sonography in the preoperative assessment of the primary tumor spread in malignant pleural mesothelioma]. / MRT, CT und Sonographie in der präoperativen Beurteilung der Primärtumorausdehnung beim malignen Pleuramesotheliom.

PURPOSE: Evaluation of the diagnostic value of the imaging modalities computed tomography (CT), magnetic resonance imaging (MRI), and thoracic sonography in the preoperative staging of malignant pleural mesothelioma. MATERIALS AND METHODS: The diagnostic accuracy of CT (n = 41), MRI (n = 24), and thoracic sonography (n = 37) were evaluated in 51 patients with histologically proven diffuse malignant pleural mesothelioma. Values of sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for the assessment of the diaphragm, lung, thoracic wall, pericardial wall, myocardium, and (retro)peritoneal space. RESULTS: The accuracy rates for CT were 85%, 98%, 83%, 73%, 71%, and 83%. MRI had an accuracy of 71%, 92%, 71%, 83%, 71%, and 96%, the thoracic ultrasound examinations of 76%, 63%, 51%, 60%, 71%, and 89%. CONCLUSIONS: According to these results CT remains the method of choice in the preoperative assessment of T-stage of malignant pleural mesothelioma. MRI is of nearly the same value, but is not a must. Sonography may be supplementary method for operation planning.

[The intracavitary administration of contrast medium in the aftercare of complicated thoracic empyema with long-term drainage: x-ray fluoroscopy compared to computed tomography]. / Die intrakavitäre Kontrastmittelgabe bei der Nachsorge des komplizierten langzeitdrainierten Thoraxempyems: Röntgendurchleuchtung im Vergleich zur Computertomographie.

PURPOSE: To define the value of conventional radiography compared with CT in the follow-up of complicated, long-term tube drained pleural empyema after intracavitary application of contrast medium. METHODS: 28 patients with complicated pleural empyema (stage III) and long-term tube drainage were submitted to fluoroscopy of the pleural cavity and a CT of the thorax after contrast medium had been instilled into the pleural space. Both examinations were judged by the following criteria: number and morphology of pleural cavities, quality of drainage and accompanying thoracic disease. RESULTS: 49 pleural cavities were diagnosed. Judgement of drainage corresponded in 79% of cases and differed in 21% with proof of further not drained cavities only on CT. 4 bronchopleural fistulas were diagnosed by fluoroscopy, of which only 2 were evident on CT. Accompanying thoracic disease was reliably detected by CT only. CONCLUSIONS: Diagnosis of bronchopleural fistulas and judgement of the pleural drainage is best possible using fluoroscopy after application of contrast medium into the pleural space. CT is most accurate to detect further cavities that have not been drained, to look for concomitant thoracic disease, and to judge the morphology of the pleural cavity. Conventional radiography of the pleural space is effective and recommended to be used as a first line investigation for the follow-up of stage III empyemas. Patients in poor general condition (fever, elevated blood markers indicating inflammation) should be examined by both fluoroscopy and CT.

[Mediastinal actinomycosis with formation of an esophagotracheal fistula. A case report]. / Mediastinale Aktinomykose mit ösophagotrachealer Fistelbildung. Ein Fallbericht.

Before antibiotics were available, actinomycosis was the most commonly diagnosed "fungal disease" of the lung because of its morphological similarity to true fungi. At that time actinomycosis presented a fairly typical clinical picture of empyema thoracis and sinus tracts in the chest wall. Nowadays it has become a rare infectious disease that is usually caused by the bacterium Actinomyces israelii and is amenable to treatment by most antibiotics available today. The following report describes the case of a 59-year-old man with an uncommon mediastinal actinomycosis that caused an oesophagotracheal fistula. This complication may develop due to the necrotizing inflammatory process that is typical for actinomycosis. With regard to the literature, the clinical manifestations of the disease and diagnostic and therapeutic considerations are discussed.

[The thoracic radiologic significance of the width of the azygous vein and its correlation with right atrial blood pressure]. / Die thoraxradiologische Bedeutung der Weite der V. azygos und deren Beziehung zum rechtsatrialen Blutdruck.

The widths of the azygos vein were measured in 150 patients and correlated with the pressure in the right heart-atrium. We found a significant logarithmic correlation (r = 0.8) between the two parameters. Radiologic measurement of the width of V. azygos in chest radiographs or CT is useful to evaluate the function of the right heart.

[Intravascular ultrasound in preoperative diagnosis of central bronchial tumors--initial clinical experiences]. / Intravasale Sonographie zur präoperativen Diagnostik zentraler Bronchialtumoren--erste klinische Erfahrungen.

In the course of preoperative diagnosis, intravasal sonography for tumour imaging was conducted in three patients suffering from central bronchial carcinoma. The catheters of 6.0 or 4.8 French diameter were advanced in each case after pulmonary angiography via the left or right pulmonary artery up to the tumour area. Endosonographic tumour imaging was compared with the findings of the other preoperative diagnostic measures and in two cases with intraoperative and postoperative findings. The vascular walls of the central pulmonary arterial segments showed sonographically no typical three-layer structure. In all cases, however, tumour infiltration was showed up by disappearance of the vascular wall reflexes in the relevant pulmonary artery branches. Visualisation of the mediastinal pulmonary artery segments or of the main stem of the pulmonary artery is difficult with the wire-guided catheters used, since these cannot be stabilised in the centre of the vessel. Development of suitable catheters with low-frequency transducers and greater depth of penetration is imperative especially for the diagnostically important visualisation of the surrounding mediastinal structures.

[MR angiography. Its use in pulmonary and mediastinal space-occupying lesions]. / MR-Angiographie. Einsatz bei pulmonalen und mediastinalen Raumforderungen.

MR angiography (MRA) proved to be promising combined to MR imaging (MRI) in the assessment of intrathoracic masses. Sequential FLASH 2D angiograms were acquired in breath-hold technique using the following parameters: TR = 30 ms, TE = 10 ms, FA = 30 degrees. Section thickness was 5 mm with 1 mm overlap between sequential sections. Individual conditions of the examination were achieved by an automatized control procedure. Targeted MIP postprocessing resulted in 3D reconstructions illustrating vascular anatomy and avoiding superimposition. Presentation should be done by cine-mode for better spatial impression. This method was evaluated in a prospective study of 21 patients with malignant pulmonary and mediastinal masses in addition to spin-echo imaging. The diagnostic contribution concerning the relationship between the mass and the vasculature like displacement, stenosis, and poststenotic perfusion defect were assessed.

Classification of lung cancer: first experiences with the new TNM classification (4th edition).

In January 1987, the 4th edition of the TNM classification for malignant lung tumours by the International Union Cancer (UICC) came into effect. Thus, for the first time, a uniform worldwide staging system for lung cancer became available. In order to validate the new TNM definitions for lung cancer the data of 3,000 patients were analysed prospectively. Several items were examined: 1) the agreement between clinically (TNM) and pathologically (pTNM) confirmed classification; 2) the value of the various diagnostic techniques estimating the pathologically confirmed classification; 3) the influence of the TNM definitions on separating distinct prognostic groups. With regard to the primary tumour (T), clinical and pathological classifications were identical in 64%; for lymph node involvement (N) the agreement was 48%; for distant metastases it was 90% and for the stages it was 55%. As for the primary tumour (T) the accuracy of radiography (59%) was nearly identical to computed tomography (58%). Both techniques were less precise in determining the extent of lymph node involvement (computed tomography 50%, radiography 43%, correct assessments). The statistically significant differences in prognosis for the various T-, N- and M-categories as well as for the stages could be confirmed. By the new 1987 TNM definitions (4th edition) for lung cancer international conformity became feasible as well as practical, and the improvement in its prognostic relevance provided, therefore, a more reliable basis for establishing guidelines for individual oncological concepts of therapy.

Clinical applications of MR angiography in intrathoracic masses.

This is a prospective evaluation of the use of MR angiography (MRA) at 1.5 T in the assessment of intrathoracic masses. Two-dimensional (2D) MRA was obtained sequentially by means of a fast low angle shot (FLASH) technique (repetition time 30 ms, echo time 10 ms, flip angle 30 degrees) one slice per breath-holding. An automated control procedure and instantaneous image reconstruction permitted constant monitoring of the image quality and tailoring of the timing of the scans to each patient's breathing capacity; MRA was successfully completed in all patients. Two-dimensional FLASH angiography was postprocessed into three-dimensional (3D) MR angiography (projections) by a maximum-intensity-projection algorithm; a 3D spatial impression of the MRA was achieved by obtaining 3D MRAs from different viewing angles and by viewing these in a cine-loop. Superimposition of vessels was avoided by creating angiograms of interest of a specific anatomic region. Fifteen patients with malignant or benign intrathoracic tumor were evaluated; their MR findings were correlated with chest radiography, conventional angiography, bolus enhanced CT, and/or perfusion scintigraphy. Magnetic resonance angiography revealed stenosis, distortion, and displacement of vessels by tumors as well as distal perfusion defects caused by proximal tumors. The MRA findings were readily accepted by our clinical colleagues and incorporated into their surgical planning. We believe MRA to be a promising complement to MR imaging in the assessment of intrathoracic masses.

[Conventional section study of thoracic organs. Improved diagnosis with compensation filters of anatomically molded acrylic glass containing lead]. / Konventionelle Schichtuntersuchung der Thoraxorgane. Verbesserte Diagnostik mit Ausgleichskörpern aus anatomisch geformtem, bleihaltigem Acrylglas.

The diagnostic value of conventional chest tomography was improved dramatically by filters, manufactured of transparent acrylic glass containing 120 or 240 mu lead aquivalent (DuPont, Neu Isenburg). A perfect compensation of the chest anatomy and pathology in ap-pulmonary tomography can be done easily because the anatomically shaped filters are mobile-mounted in front of the x-ray tube. The position of each filter is visible on the patient's skin. This enables the radiographer to routinely obtain tomograms with diagnostic density values ranging from S = 0.4-2.0. For 6 characteristic areas this was measured in 98%. Such films allow subtle analyses of the tracheal and bronchial wall, the segmental bronchi and pulmonary vessels or pathologic lesion. Compared to cross-sectional imaging CT and MRT, the frontal tomogram shows several aspects of the hilar compartment more clearly because the main central pulmonary structures are located primarily craniocaudally. The conventional tomogram therefore supplies additional views with high spatial resolution. The clinical importance of diagnostic information obtained with ap-tomography using the ATCF are shown in 4 cases. In our hospital, the thoracic surgeon therefore demands conventional tomography with the ATCF to complete staging of benign or malignant chest disease preoperatively.