Volume 28, Issue 2

Background: Response evaluation by standard imaging procedures such as computed tomography (CT) may be difficult in patients undergoing chemotherapy for advanced and metastatic pancreatic cancer. The aim of the study was to determine whether kinetics of CA19-9 levels can replace imaging procedures in evaluating the response to chemotherapy in these patients. Patients and methods: Patients with advanced or metastatic pancreatic cancer were included in the study. Patients received a combination chemotherapy consisting of gemcitabine (1000 mg m −2 d1, 8, 15) and cisplatin (50 mg m −2 d1, 15) repeated on day 29. Treatment was continued until unacceptable toxicity or disease progression occurred. CA19-9 levels were measured directly before each cytotoxic treatment cycle. CA19-9 response was defined by a ≥50% decrease in CA19-9 serum levels within two months after treatment initiation. Results: A total of 77 patients with initially elevated CA19-9 levels were included for evaluation (f/m = 26/61; stage 3/4 = 24/63). Out of 15 patients who had responded to chemotherapy regarding imaging criteria (CR 4, PR 11, OR 19.5%), 14 patients were classified as CA19-9 responders. Although 62 patients had not responded to chemotherapy by CT-imaging criteria, 29 patients fulfilled the criterion of a CA19-9 responder. The low value of CA19-9 kinetics in predicting imaging results (positive predictive value 32.5%) seems to be clinically irrelevant since CA19-9 responders, independent of imaging criteria, have a significant improvement of survival time compared to non-responders (295 days; 95%CI: 285–445 vs 174 days; 95%CI: 134–198; p = 0.022). Conclusion: CA19-9 kinetics are unable to predict tumor response regarding imaging criteria. However, the kinetic of CA19-9 in a patient undergoing chemotherapy for pancreatic cancer seems to be a reliable indicator in predicting survival.

Management of testicular tumor patients without marker assessment is unacceptable in these days. Markers are included in the TNM scheme since 1997 in form of the S classification. The combination of AFP, hCG, LDH and PLAP shows high specificity and sensitivity, in contrast to most tumor markers in other malignancies. While preoperative markers are usually available, it is less common to monitor the immediate postoperative course. Still there are patients with the first control of tumor markers four weeks after surgery. In patients showing normal markers after four weeks, one may have missed a prolonged marker decline, such overlooking remaining tumor tissue which could have been treated more easily if detected in time, and not as late as metastases can be identified by imaging alone. If markers have not normalized after four weeks, there is a substantial delay in starting adjuvant treatment with a probable decreased chance for cure of the disease. Furthermore, tumor markers are important for classifying the risk of primary metastatic disease as well as for evaluation of response to chemotherapy. Marker normalization is a prerequisite for successful post-chemotherapy surgery. During follow-up, rising markers are able to identify relapsing tumors at an earlier stage than imaging techniques alone.

Fuzzy-based procedures of multiparametric pattern recognition have been established in technical diagnostics and industrial automation for more than 10 years. The consideration of fuzziness has broken new ground in computer-aided decision support which still goes on successfully today. The capability of this methodology significantly benefits from the inclusion of knowledge, experience, and applied examples. A further advantage of these procedures consists in the terminological transparency and ease of comprehension. Instead of abstract mathematical formulas, the algorithms are described by verbal rules. This aspect particularly facilitates the interdisciplinary cooperation between users and mathematicians, and in this way facilitates a time- and cost-effective system development as well. However, the utilization of fuzzy systems is effectual only if the problem is suitable for fuzzy treatment. As an example, these requirements are examined in the analysis of tumor marker profiles. The illustration of basic ideas and principles provides the understanding of the mathematical data evaluation without direct confrontation with algorithms. As a result, an increase of sensitivity on high specificity is achievable. The particular steps of calculation seem to conform to the subjective decision making when tumor markers are analyzed.

Pituitary adenomas are rare benign tumors with delayed manifestation which can include headaches and symptoms of nerve compression, such as visual field disturbances or endocrine dysfunction. Endocrine abnormalities can be the result of overproduction of pituitary hormones, pituitary insufficiency, or a combination of both. The evaluation of suspected pituitary tumors should include the determination of the presence and type of hormone hypersecretion as well as hyposecretion, combined with pituitary imaging. Screening for pituitary dysfunction is achieved by assessing the pituitary and target hormone concentrations in blood, maybe followed by dynamic tests of the pituitary function.

Growth hormone (GH) is synthesized in the anterior lobe of the pituitary gland and has a plasma half-life of 19 minutes. GH-secretion is regulated by hypothalamic releasing hormone (GHRH) stimulation and somatostatin inhibition. The major effect of GH is the stimulation of insulin-like growth factor-1 (IGF-1) synthesis and secretion by the liver. However, GH also has other biological effects through other mediators. Serum-IGF-1 is bound to IGF binding protein-3 (IGFBP-3) and to acid-labile subunit (ALS). The GH/IGF-1-axis is evaluated when either GH-deficiency (GHD) or GH-excess (acromegaly) are suspected. GHD is confirmed by a diminished GHresponse to insulin-induced hypoglycemia (normal range GH >5 μg/l) or to administration of GHRH+arginine (normal range GH >9 μg/l). Acromegaly has distinct clinical signs and is confirmed when GH can not be suppressed below 1 μg/l by an oral glucose tolerance test in combination with elevated IGF-1 levels adjusted for age.

Primary aldosteronism, characterized by hypertension and low-to-normal potassium levels, has lately been recognized as a rather frequent cause of secondary hypertension. The two principle reasons for primary aldosteronism are bilateral adrenal hyperplasia and aldosterone-producing adenoma. Screening for primary aldosteronism is performed by measuring the aldosterone/ renin ratio, which has good accuracy even if the patient is under medication. The diagnosis needs to be confirmed by further diagnostic procedures and, since the therapy of the subtypes varies, differential diagnosis is required. Bilateral adrenal hyperplasia is treated through medication, whereas hypertension due to adenoma can be cured or improved by adrenalectomy.

Chlamydiae are obligate intracellular bacteria undergoing a unique growth cycle which is important for the special features of diagnosis, therapy and pathogenesis of chlamydial infections. Mainly Chlamydia trachomatis , Chlamydia pneumoniae and Chlamydia psittaci cause infections in humans. The clinical relevance of chlamydia- like species such as Simkania , Waddlia and Parachlamydia is unclear and currently under investigation. In principle, laboratory diagnosis of chlamydial infections can be achieved by direct detection of the organisms from clinical specimens and antibody detection. The selection of suitable laboratory tests depends on the chlamydial species and the clinical presentation of infection. Culture tests have been proven to be highly specific, however due to the high level of technical expertise necessary, chlamydial cultures are generally performed in specialized reference laboratories. Nucleic acid amplification technologies are characterized by their high sensitivity and have been broadly evaluated for the detection of C. trachomatis from urogenital specimens. In contrast, standardization of DNA amplification methods for detection of C. pneumonia is urgently needed to evaluate the importance of the organism in respiratory diseases, as well as in associated extrapulmonary diseases like atherosclerosis. Serodiagnosis of chlamydial infections should be based on species-specific methods like the technically demanding microimmunofluorescence test (MIF). Commercially developed MIF assays, peptidebased EIAs and immunoblot assays are still in a phase of evaluation and may contribute to a more standardized serodiagnosis of Chlamydia infections.

Background: Syphilis is among the infections that are characterized best by serologic methods. Nevertheless, in single cases evaluation may be difficult. The aim of this study was to investigate the avidity of specific IgG to achieve additional information. Patients and methods: In 182 previously analyzed sera from syphilitic patients the avidity of Treponema pallidum - specific IgG was estimated by means of ELISA (endpoint detection). Results: Treponema pallidum -specific IgG reached postinfectious avidity values of 20% after about four weeks and of 40% after six months without therapy. Values above 60% could be detected only in special cases. Between avidity and specific IgM–but not avidity and Cardiolipin microflocculation test -, a reverse proportional relationship exists. Persistence of specific IgM is evidenced by the avidity values. Conclusions: Avidity detection of specific IgG gives evidence of the time of primary infection. The estimation of avidity besides conventional diagnostics in syphilis may confirm cases suspected of reinfections, give additional information in problematic cases or in cases for an expert's certificate.