Acta medica Austriaca. Supplement最新文献

There are different reasons why the detection of disseminated tumor cells (DTCs) in the hematopoetic system is important. On the one hand the detection of disseminated tumor cells can provide vital information about a tumor's tendency to develop metastases. In some localized epithelial but also in embryonic tumors, for example a correlation between disseminated tumor cells and unfavorable outcome was observed (6, 14). These studies are based on the assumption that those tumor cells which appear in the hematopoetic system at a very early stage are responsible for the development of metastases. Another important aspect is the monitoring of the disease response to cytotoxic drugs by quantifying DTCs. During and after therapy there is no other possibility (except for an operation) to either directly analyze the effects the therapy has on the tumor cells or to determine their biological characteristics. The dissemination in the hematopoetic system, however, reveals the response to therapy and the biological features of the tumor cells. The prerequisites for such bone-marrow diagnosis, however, is the unequivocal identification of disseminated tumor cells. So in order to avoid false positive results (which are a risk in bone-marrow diagnostics), a system was developed to distinguish tumor cells from non-neoplastic cells and to facilitate insights into the biological make-up of tumor cells (2, 11).

Cancer mortality has only marginally decreased in the last decades despite huge diagnostic and therapeutic efforts. Early dissemination of cancer cells has to be blamed for this finding, because ectopically residing cells are necessarily left behind by the surgeon. Consequently, this cell population has been designated as minimal residual disease that may eventually lead to systemic relapse months or years after presumed curative surgery. Paradoxically, systemic adjuvant treatments are currently administered without any precise knowledge about the target population of such drugs. Here it is argued that the direct analysis of disseminated cells may be a prerequiste for the development of future therapies since first molecular genetic data of single disseminated cancer cells suggest an excessive intercellular heterogeneity and distant relationship to the primary tumor.

Cytoreductive therapy can ameliorate symptoms in chronic myeloid leukemia (CML) but only treatment beyond hematologic remission aiming to affect the leukemic clone can improve prognosis. Up to now bone marrow transplantation is the only established therapy with the potential to completely eliminate the BCR-ABL positive cell population. Interferon-alpha (IFN-alpha) as well as cytosine arabinoside (ARA-C), particularly in combination, have been shown to be effective in achieving cytogenetic remission in some patients. With Glivec (STI-571) there is now a drug available which can induce major cytogenetic response in more than half of the patients who have failed IFN-alpha treatment and thus possibly delay or prevent blast crisis. Recent reports, however, have shown that primitive, quiescent, Philadelphia-positive stem cells are insensitive to STI-571 in vitro. Such cells could be the basis of relapse after termination of Glivec-therapy.

In Austria in 1999, a Diabetes screening program was carried out by the Austrian Diabetes Association and by Novo Nordisk and Roche Diagnostics with a special equipped bus touring through more than 90 cities. The population was invited to a screening of blood glucose (random), blood pressure, body weight und serum-cholesterol. The diabetes risk was evaluated by history and familiar burden with a questionnaire. The results were handed over to the visitors and their general practitioners, and a copy was used for anonymously analysis.

Immunocytochemical and molecular biological methods to analyze minimal residual disease (MRD) in colorectal cancer in blood and bone marrow were compared. The concept of a study in the Donauspital will be presented which will permit a comparative judgement of minimal residual disease in blood and bone marrow in patients with colorectal cancer.

The occurrence of occult metastases of solid tumors at initial diagnosis or during follow-up is of crucial therapeutical importance. The sensitive detection of such cells in hematological samples depends on tissue specific cellular markers. The demonstration of minimally disseminated tumor cells at a given timepoint is, however, only a snapshot, which does not give any information about the potential and dynamics of the cells in question. Functional differences may fundamentally influence the impact of a positive finding. The analysis of cell proliferation and cell death (apoptosis) in disseminated tumor cells, for instance, defines, whether the dissemination process is progressive or regressive. With a newly developed automatic image analysis station the investigation of functional parameters in isolated cells from clinical samples became possible. The studies presented here demonstrate, that such techniques allow an improved identification of isolated tumor cells with clinical importance.

In comparison to non-diabetic normotensive control subjects, hypertensive diabetic patients have a four-fold increased risk for cardiovascular morbidity and mortality. Additional to WHO/IHS definition, the terminus "high-normal blood pressure" (systolic 130-140 mm Hg and diastolic 85 - < 90 mm Hg) was used for data analysis. The mean blood pressure was elevated among diabetic subjects (157/85 mmHg) when compared to the non-diabetic group (141/82 mm Hg). The analysis of visitors with an already known diabetes yielded only 14% of probands having normal blood pressure, whereby 63% of diabetic subjects were definitely in the hypertensive range. In overweight (BMI > 28 kg/m2) subjects, whose percentage in our population were 32%, blood pressure was elevated (RR > 150/90) in 51%. In subclasses with high blood pressure, an increased cholesterol level was often seen; 64% of these subjects had a cholesterol level of greater 200 mg/dl.

The clinical course of cervical carcinoma is widely determined by locoregional recurrence. There is increasing data, however, that haematogenic micrometastases occur early during the disease and might result in distant recurrence during follow-up. These occult disseminated tumor cells in blood, lymph nodes and bone marrow escape conventional tumor staging. Therefore, molecular and immunoytochemical techniques based on markers against human papilloma virus or cytokeratins (CK) have been applied. At present, there is only one study available on the prognostic relevance of disseminated tumor cells in bone marrow. No correlation between the bone marrow status and overall survival was observed. Still, there was a strong trend towards shorter distant disease free survival in patients with a positive bone marrow status. In view of the data on disseminated tumor cells in other tumor entities, these early results might offer new options for refined tumor staging and improved treatment options.