Band 31, Heft 2

During the last two decades the laboratory diagnostics of virus infections has achieved essential importance. In addition to low-cost examinations, it is important for the doctor and patient to obtain fast and correct laboratory results. The correctness of the results depends on different factors. The suitability and efficiency of the test and/or examination procedure under consideration are of particular importance. According to the ISO 15189 “Medical laboratories – special requirements for quality and competence” and the guideline for in vitro diagnostic medical devices (IvD Directive) only tests and/or examination procedures may be used for which suitability and capability could be demonstrated. Requirements for suitability and efficiency or the so-called validation is only generally addressed in both documents. Therefore, a guideline for virus diagnostics has been developed where the requirements for validation are described in detail. The guideline distinguishes between the validation of commercial tests, in-house tests, and the different examination methods used in virus diagnostics.

The International Standard EN ISO 15189 (in short ISO 15189) provides requirements for competence and quality that apply to medical laboratories. The ISO 15189 applies to all medical laboratories. For virology this standard has been established by a joint working group of the German Society of Virology (GfV) and the German Association Against Virus Diseases (DVV) in the form of check lists. Numerous medical laboratories get the fulfilment of the requirements of ISO 15189 confirmed by accreditation. A substantial part of the accreditation process is the onsite assessment in the laboratories. In the case of virology, this assessment is performed by experts appointed by the GfV. Laboratories may have very different reasons for accreditation. These range from the improvement of the internal processes and determination of reliable examination results to better positioning at the market. The article presented here is a field report outlining the requirements and problems for laboratories in medical virology – based on ISO 15189 – thereby addressing the issues of serology, molecular-biological diagnostics and virus isolation on cell cultures.

The working group on „Molecular Diagnostics of Pathogens” of the Austrian Society for Good Analysis and Laboratory Practice published a guideline for molecular diagnostics of pathogens for the first time in 1998. The original version was updated in 2001. The medical progress in general as well as the implementation of the in vitro diagnostics guideline (98/79 EC) in December 2003 urged another update. The present update helps to ensure proper molecular diagnostics of pathogens in qualified laboratories according to the state-of-the-art.

Calculations exemplarily prove the possibility to apply tumour markers to reduce the increasing costs in lung cancer screening. Sequential analysis of tumour markers is a potential target for cost-cutting effects by reducing the diagnostic procedure. In combination with new mathematical techniques of data analysis, the advantage of the method is demonstrated and the economical aspects are calculated. Cost-accounting systems are dependent on the screened persons and the available diagnostic methods. Statistical cost analyses are not restricted to tumour markers but could also include computed tomography or sputum analysis for potential lung cancer screening. It is therefore possible to discuss the alternative diagnostic procedures in lung cancer screening in consideration of economic aspects.

Background: The aim of our descriptive analysis was to determine the correlation between disease progression in metastatic breast cancer and the tumor markers carcino-embryonic antigen (CEA) and cancer antigen (CA) 15-3. Patients and methods: We retrospectively analyzed the history and medical findings of patients who were treated between 1992 and 2004 at the University Hospital Munich Großhadern. We evaluated pre-treatment values of CEA and CA 15-3 at the time of first metastatic disease (1st MD) and at every time of disease progression (1st to 5th PD). We investigated 71 patients at 1st MD, 85 at 1st PD, 86 at 2nd PD, 72 at 3rd PD, 62 at 4th PD and 47 patients at 5th PD, respectively. It was possible that patients qualified more than once for evaluation. Results: A trend of increasing levels of CEA and CA 15-3 in correlation to disease progression was established. Median concentration was 2.7 ng/mL for CEA and 43.8 U/mL for CA 15-3 at 1st MD. During disease progression the values for CEA/CA 15-3 were: 2.8 ng/mL/44.7 U/mL at 1st PD; 4.1 ng/mL/65.4 U/mL at 2nd PD; 5.2 ng/mL/94 U/mL at 3rd PD; 8.2 ng/mL/97 U/mL at 4th PD and 8.8 ng/mL/139 U/mL at 5th PD, respectively. We also obtained a continuously increasing percentage of true positive test results with increasing numbers of disease progression for both tumor markers. The combined determination improved sensitivity from 80.3% at 1st MD to 95.7% at 5th PD for detection of disease progression. Conclusions: Our results demonstrate a correlation between release of tumor markers and disease progression. The combination of both markers leads to increased sensitivity.

Background : In addition to carcino-embryonic antigen (CEA), several oncological biomarkers have been described to be of prognostic relevance in colorectal cancer. Currently, it is still unclear which of these markers are able to provide additive information to established prognostic factors in non-metastatic colorectal cancer. Methods : We investigated whether tumor markers have additive prognostic value to tumor stage in 458 patients with non-metastatic colorectal cancer. Preoperative serum levels of CEA, cancer antigen (CA) 19-9, CA 242, CA 72-4, CYFRA 21-1 and human chorionic gonadotropin (hCGβ) were analyzed. Results : For evaluating disease-free survival (DFS) and overall tumor-related survival (OTS), based on recommendations for adjuvant treatment, patients were divided into the good prognosis group (GPG: colon cancer stage I-II or rectal cancer stage I) and the bad prognosis group (BPG) consisting of the remaining patients with indication for adjuvant treatment. Evaluating tumor markers, linearity was tested. In case of non-linearity a cut-off value was determined. Log (CEA) showed linearity in the GPG and BPG. In the GPG, CEA was the only significant tumor marker, whereas in the BPG, CEA, CA 19-9, CA 242 and CA 72-4 were significant predictors. In multivariate Cox regression analysis, T stage (T3 or T4) and CEA proved independent relevance in the GPG, whereas T4, N2, site, CEA and CA 19-9 were independent predictors in the BPG. Conclusions : CEA and possibly CA 19-9 have additional prognostic value besides tumor stage and, therefore, should be included in the decision for adjuvant treatment. Zusammenfassung Fragestellung : Neben dem carcinoembryonalen Antigen (CEA) wird mehreren onkologischen Biomarkern eine prognostische Relevanz beim kolorektalen Karzinom zugeschrieben. Derzeit ist unklar, welcher dieser Marker zusätzlich zum Tumorstadium eine prognostische Information geben kann. Methoden : Wir untersuchten anhand präoperativer Proben von 458 Patienten mit nicht metastasiertem kolorektalen Karzinom, ob CEA, Cancer Antigen (CA) 19-9, CA 242, CA 72-4, CYFRA 21-1 und humanes Chorion-Gonadotropin (hCGβ) eine additive prognostische Aussagekraft zusätzlich zum Tumorstadium besitzen. Ergebnisse : Um das disease free survival (DFS) und overall tumor-related survival (OTS) beurteilen zu können, wurden die Patienten entsprechend der aktuellen Empfehlungen für adjuvante Therapien in zwei Gruppen unterteilt, in eine “good prognosis group” (GPG: Colonkarzinom Stadium I-II oder Rektumkarzinom Stadium I) und eine „bad prognosis group” (BPG), die sich aus den übrigen Patienten mit einer Indikation für eine adjuvante Therapie zusammensetzte. Bei der Evaluierung der Tumormarker wurde zunächst die Linearität getestet. Bestand kein linearer Zusammenhang, so wurde ein cut off bestimmt. Der Logarithmus von CEA zeigte sowohl für die GPG als auch für die BPG Linearität. In der GPG war CEA der einzige signifikante Marker, während in der BPG CEA, CA19-9, CA 242 und CA 72-4 signifikant waren. In der multivariaten Cox Regressionsanalyse erreichten in der GPG die Tumorinfiltrationstiefe T (T3 oder T4) und CEA unabhängige prognostische Relevanz, während in der BPG T4, N2, die Tumorlokalisation, CEA und CA 19-9 unabhängige Prädiktoren waren. Schlussfolgerung : CEA und möglicherweise CA 19-9 haben zusätzlich zum Tumorstadium prognostische Aussagekraft und sollten deshalb in die Entscheidung zur adjuvanten Therapie mit einbezogen werden.