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.

[Comparison of densitometric and morphometric measurements of global and regional functions using a fully digital subtraction unit]. / Vergleich densitometrischer und morphometrischer Messungen globaler und regionaler Herzleistungen mit einer volldigitalisierten Subtraktionseinheit.

The value of digital subtraction angiocardiography for evaluating left ventricular movement by a morphometric and densitometric technique was examined by animal experiments (dog). Reversible reduction of global and regional left ventricular function can be quantified by both methods equally well. For judging regional ejection fraction, sector display is more easily comprehended than an ejection-fraction map. For the estimation of global cardiac ejection fraction in 49 patients, morphometric diagnosis was clearly superior to cine cardio-angiography (rmorp. = 0.91; rdens = 0.65). For recognising and quantifying regional abnormalities of cardiac movement, semi-quantitative visual gradation is superior to densitometric measurements.

[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.

[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.

[Evaluation of intrapulmonary round foci using thin-layer computed tomography]. / Die Beurteilung intrapulmonaler Rundherde mit Hilfe der Dünnschichtcomputertomographie.

100 patients with 122 round pulmonary lesions were examined preoperatively by CT, using either 8 mm or 2 mm sections. The most important findings were: radial extensions were seen on the fine sections in 95% of primary bronchial carcinomas (48 cases), in 60% of lung metastases (31 cases) and in 70% of chronic inflammatory lesions (24 cases), but they were not seen in benign tumours or hamartomas. Similar findings were observed for perifocal consolidation. Calcification was found in 80% of the tuberculomas (15 cases) and in 37% of the hamartomas (8 cases), but it also occurred in 15% of the primary bronchial carcinomas and in almost 13% of the lung metastases. Thin section CT provided more information than did 8 mm sections in 44% patients, concerning the outline of the lesion, and in 60% it was better at showing calcification. It was not possible to define a pattern of calcification which would distinguish benign from malignant lesions.

[Determination of global and regional ventricular ejection fraction by a fully digitalized technic. Results of digital subtraction angiocardiography following peripheral venous contrast injection compared to cineventriculography, 2-dimensional echocardiography and radionuclide ventriculography]. / Bestimmung der globalen und regionalen Auswurffraktion des linken Ventrikels in volldigitalisierter Technik. Ergebnisse der digitalen Subtraktionsangiokardiographie (DSAK) nach periphervenöser Röntgenkontrastmittelinjektion im Vergleich zur Kineventrikulographie, Zweidimensionaler Echokardiographie und Radionuklidventrikulographie.

Subtraction angiocardiography (DSAK) with a fully digitalised system (DR 960) provides a well defined demonstration of the left ventricle after peripheral venous contrast injection. Cardiac volume and ejection fractions were calculated by a dedicated software programme and the findings correlated with cine ventriculography (CA) (r = 0.91), biplane echo cardiography (2 DE) (r = 0.77) and radionucleid ventriculography (RNV) (r = 0.85); the method can be used even with reduced cardiac output (EF less than or equal to 15%). Densitometric measurements of the EF on phantoms correspond with morphometric findings, but its clinical application is at present not possible because of the frequent appearance of artefacts. Analysis of regional disturbances of ventricular wall movements shows very good correlation between DSAK and CA and these appear more accurate than 2 DE. DSAK is a valuable, rapid and reproducible method with few side effects for cardiological diagnosis.

[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.

[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.

[Conventional roentgen study in the diagnosis of primary and secondary chest wall tumors]. / Konventionelle Röntgenuntersuchung in der Diagnostik primärer und sekundärer Brustwandtumore.

In patients with chestwall tumors conventional radiography is most often the next diagnostic step for differentiation and staging. Plain chest films, taken according to ILO-80 regulations, fluoroscopy and x-rays of the bony structures of the thorax are basic examinations. Diagnostic features are intra- and extrathoracic soft tissue masses and/or disturbances of normal fat pads. CT and/or MR are superior for analyzing soft tissue masses and cannot be missed. But bone lesions are better to analyze on conventional x-rays. Skeletal scintigraphy helps to increase the effectivity and is requested before tomography. Invasive diagnostic procedures (phlebography, arteriography, myelography, bronchography) should be performed only after CT- or MR-examinations. They can add important diagnostic details. Selective arteriography enables the radiologist to embolize vessels of large tumors preoperatively, reducing surgical risks, or may be helpful in patients with non-resectable tumors.

[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.

[Infusion urography with joxitalmat comparative study with different infusion solutions (author's transl)]. / Infusionsurographie mit Joxitalmat Vergleichende Untersuchungen mit verschiedenen Infusionslösungen.

In a total of 157 patients, comparative infusion urography was conducted using different concentrations of the same infusion substance Joxitalmat (Telebrix). No fatal or severe side effects caused by the contrast medium were seen. Infusion of the 66% contrast medium solution C produced mild side effects in 9% of the patients, whereas 4% resp. 2% side effects occurred with the solutions A (39.7%) and B (36.6%). Hence, solutions A and B appear to be more appropriate for clinical diagnostics, the diagnostic value being approximately the same for all three solutions under investigation.

[Digital subtraction angiography of aortocoronary bypass grafts in the early postoperative phase with peripheral vein x-ray contrast media injection]. / Digitale Subtraktionsangiographie (DSA) aortokoronarer Bypass-Grafts in der frühen postoperative Phase bei peripher-venöser Röntgenkontrastmittel-Injektion.

Using a fully digitalised subtraction unit, aortocoronary bypass grafts can be visualised in the early postoperative phase by means of peripheral venous contrast medium injection (57 out of a total of 60 cases). In more than one-half of the cases (31 out of a total of 60), it is possible to outline sharply the bypass grafts from the beginning to their entry into the bridged-over coronary artery, in such a manner that any loops, kinks, stenoses or reduced flow rates can be recognised. This examination is not considered to be an invasive one by the patient, and the cardiosurgeon can welcome it as a valuable additional means of controlling and assessing the results of surgery.

[Anatomically shaped, unsharp, lead-containing acrylic glass filter for optimization of thoracic roentgenography]. / Anatomisch geformtes unscharfes bleihaltiges Acrylglasfilter zur Optimierung der Röntgenthoraxaufnahme.

Acrylic glass filters fitted near to the tube and shaped according to the patient's anatomy with a lead equivalent of 120 mu enhance the diagnostic value of a plain radiograph of the chest with 95% of the patients. The pulmonary vessels and mediastinal structures can be assessed on film. Compared with the X-ray film without filter, the pulmonary vessels are visualised with equal clarity. Accurate adjustment of the patient is facilitated by the fact that the filter limits show up in the light viewfinder. Repeat X-ray films are necessary in less than 2% of the case. Artifacts are caused by anatomical chest variations as well as by large patients, and hence the use of the filter should be omitted in about 5% of the patients.

Diffuse pulmonary ossification associated with metastatic melanoma of the lung.

A case with advanced diffuse pulmonary ossification is described. The patient underwent surgical treatment of a malignant nodular melanoma of the right shoulder followed by postoperative cytostatic therapy for 6 months. He developed renal insufficiency and pulmonary infiltrates 3 years after the operation. Two metastases into the lung were operated 4 years after extirpation of the melanoma. Histopathological findings revealed two major metastases of a malignant amelanotic melanoma and multiple tumour thromboses in lymphatic and venous vessels. Severe interstitial lung damage including diffuse pulmonary ossification and focal interstitial fibrosis was noted. Morphometric measurements of ossified nodules revealed increased ossification in fibrotic lung areas. Immunohistology for differentiating immunoglobulins and lymphocytic subpopulations was insuspicious. The findings suggest that diffuse intraalveolar ossification is probably not related to pulmonary congestion.