A. Scharf

Early detection of decreased soluble HLA-G levels in the maternal circulation predicts the occurrence of preeclampsia and intrauterine growth retardation during further course of pregnancy.

Soluble (s) HLA‐G1/G5 molecules may potentially affect immune homeostasis during pregnancy. The aim of this study was to determine changes of sHLA‐G1/G5 plasma levels throughout normal pregnancy and to assess its predictive value for the occurrence of characteristic gestation‐associated diseases during further course of pregnancy.

Intratumoral Cytokines and Tumor Cell Biology Determine Spontaneous Breast Cancer–Specific Immune Responses and Their Correlation to Prognosis

Spontaneous immune responses in cancer patients have been described. Yet their clinical relevance and the conditions for their generation remain unclear. We characterized conditions that determine immune responses in primary breast cancer patients. We used tetramer analysis, ex vivo IFN-gamma ELISPOT, cytotoxicity assays, and ELISA in 207 untreated patients and 12 Her-2/neu-specific CD8 T-cell lines to evaluate tumor-specific T cells (TC) in the bone marrow or MUC1-specific antibodies in the blood. Multiplex analysis was performed to quantify 27 intratumoral cytokines, chemokines, and growth factors. Results were compared with multiple pathologic and clinical parameters of the patients and tumors. Forty percent of the patients showed tumor-specific TC responses. These correlated with tumors of high differentiation, estrogen receptor expression, and low proliferative activity, and with a reduced cancer mortality risk. High tumor cell differentiation correlated with increased intratumoral, but not plasma, concentrations of IFN-alpha and reduced transforming growth factor (TGF)beta1. In an in vitro priming experiment these two cytokines increased or inhibited, respectively, the capacity of dendritic cells to induce tumor-reactive TC. Tumor-specific B-cell responses, mainly of IgM isotype, were detectable in 50% of the patients and correlated with advanced tumor stage, increased TGFbeta1, reduced IFN-alpha, and absence of TC responses. We show here that different types of immune responses are linked to distinct cytokine microenvironments and correlate with prognosis-relevant differences in tumor pathobiology. These findings shed light on the relation between immune response and cancer prognosis.

Placental Abruption Is Associated with Decreased Maternal Plasma Levels of Soluble HLA-G

During pregnancy the fetus represents a semi-allograft. Both membrane-bound and soluble forms of the nonclassic human leukocyte antigen (HLA)-G protect the fetus from maternal immune attack. To assess the relevance of soluble HLA-G (sHLA-G) levels in the maternal circulation for the occurrence of characteristic pregnancy disorders, we analyzed sHLA-G plasma levels of women with normal and pathological pregnancies. Compared to normal pregnancy, significantly increased sHLA-G levels were detected in women delivered preterm because of intrauterine activation (uncontrollable labor, rupture of fetal membranes, cervical insufficiency) and women with Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP) syndrome. Contrary to these disorders, the sHLA-G levels in women with placental abruption were more than three times lower than in normal pregnancy (p < 0.0001). Nonparametric discriminant analysis showed that women with sHLA-G levels below 9.95 ng/mL had a relative risk of 7.12 for the development of placental abruption during further course of pregnancy. These results suggest that the occurrence of pregnancy-associated diseases is strongly influenced by maternal sHLA-G plasma levels.

3D Real-Time Imaging of the Fetal Heart

Objective: The aim of this study was to evaluate the clinical utility of a novel 3D scanner system for real-time 3D fetal echocardiography. Method: In a prospective study, 13 single, healthy 20- to 24-week-old fetuses were examined with conventional 2D and real-time 3D echocardiography. The visualization rates and imaging quality of standard cardiac views were compared between both methods. Results: The visualization rates of standard cardiac planes were found to be slightly increased and more easily obtainable in 3D imaging whereas the image quality showed better results with conventional 2D echocardiography. Conclusion: Our data show that real-time 3D fetal echocardiography can be considered a useful tool in the evaluation of the fetal heart with the necessity for further refinement of the resolution quality

Interobserver reliability of automated breast volume scanner (ABVS) interpretation and agreement of ABVS findings with hand held breast ultrasound (HHUS), mammography and pathology results

OBJECTIVES Handheld breast ultrasound (HHUS) lacks standardization and reproducibility. The automated breast volume scanner (ABVS) could overcome this limitation. To analyze the interobserver reliability of ABVS and the agreement with HHUS, mammography and pathology is the aim of this study. METHODS All 42 study participants (=84 breasts) received an ABVS examination in addition to the conventional breast diagnostic work-up. 25 breasts (30%) showed at least one lesion. The scans were interpreted by six breast diagnostic specialists blinded to results of breast imaging and medical history. 32 lesions received histological work-up: 20 cancers were detected. We used kappa statistics to interpret agreement between examiners and diagnostic instruments. RESULTS On the basis of the Breast Imaging Reporting and Data System (BI-RADS) classification of the 84 breasts an agreement (defined as ≥4 of 6 examiners) was achieved in 63 cases (75%) (mk=0.35) and even improved when dichotomizing the interpretation in benign (BI-RADS 1, 2) and suspicious (BI-RADS 4, 5) to 98% (mk=0.52). Agreement of ABVS examination to HHUS, mammography and pathology was fair to substantial depending on the specific analysis. CONCLUSIONS The development of an ABVS seems to be a promising diagnostic method with a good interobserver reliability, as well as a comparable good test criteria as HHUS.

Evaluation of Two-Dimensional versus Three-Dimensional Ultrasound in Obstetric Diagnostics: A Prospective Study

Objectives: We aimed to find answers to the following questions: What are the technical and biological prerequisites for easily obtainable three-dimensional (3D) images? What are the visualization rates for various fetal organ systems? What is the potential for assessing fetal malformations? What are the psychological effects of 3D imaging on the expectant mothers? Methods: Between January and June 1998, 433 pregnant women were prospectively examined with two-dimensional (2D) and 3D sonography. Results: 3D visualization in healthy fetuses was inferior in quality to 2D visualization, which also accounted for the comparison of 3D imaging versus 2 D imaging among fetuses affected with malformations. In only 1 case did 3D imaging yield a slightly better description of the given malformation. This did not result in a different therapeutical approach. Concerning the psychological effect of 3D imaging, a marked approval of the 3D method was recorded. Conclusions: These results show that the image information acquired by 3D ultrasound technology is nearly always inferior to the image information obtained by conventional 2D imaging. 3D imaging can be useful for specific malformations under the condition that these examinations be performed in specific ultrasound departments. Thus, a clearly defined range of indications can be assigned to 3D imaging.

Prediction of axillary lymph node status of breast cancer patients by tumorbiological factors of the primary tumor.

Background and Purpose:The increasing use of systemic adjuvant therapy even in lymph node-negative breast cancer patients and breast cancer screening programs detecting smaller tumors with less probability of metastatic lymph nodes questions the need for routine axillary lymph node dissection. Since morbidity of breast cancer surgery is predominantly related to axillary lymph node dissection, predictive models for lymph node involvement may provide a way to avoid lymph node surgery and its side effects in subgroups of patients.Patients and Methods:Using a multivariate logistic regression model, tumorbiological parameters such as expression of estrogen and progesterone receptors, Ki-67, p53, cathepsin D, HER2, S-phase fraction, and ploidy were analyzed regarding their ability to predict axillary lymph node involvement in 655 breast cancer patients.Results:The model correctly predicted axillary lymph node metastases in 58% of the patients by including expression of progesterone receptor, HER2, and Ki-67. In a subgroup of 200 patients predicted to be at extremely high or extremely low risk for axillary lymph node metastases, the accuracy of the prediction was 70%.Conclusion:With a model just based on tumorbiological parameters obtained in the primary tumor it is possible to predict axillary lymph node status. By including additional parameters it appears to be feasible to further improve the model in order to avoid axillary lymph node surgery in low-risk women.Hintergrund und Ziel:Die zunehmende Anwendung adjuvanter Therapien auch bei nodal negativen Mammakarzinompatientinnen sowie die im Rahmen von Screeningprogrammen immer frühzeitigere Entdeckung kleiner Mammakarzinome mit geringer Wahrscheinlichkeit einer axillären Lymphknotenmetastasierung stellen den Nutzen der axillären Lymphonodektomie zunehmend in Frage. Da die axilläre Lymphonodektomie maßgeblich für die Morbidität der Mammakarzinomoperation verantwortlich ist, stellt sich die Frage, ob das Risiko eines axillären Lymphknotenbefalls für Subgruppen von Mammakarzinompatientinnen präoperativ vorhergesagt werden kann.Patienten und Methodik:Mit Hilfe einer multivariaten logistischen Regression wurden tumorbiologische Parameter (Expression von Östrogen- und Progesteronrezeptoren, Ki-67, p53, Cathepsin D, HER2, S-Phasen-Anteil, Ploidie) in Bezug auf ihre Vorhersagekraft für den axillären Lymphknotenstatus bei 655 Patientinnen mit primärer Mammakarzinomerkrankung untersucht.Ergebnisse:Das Modell konnte in 58% der Fälle bei Einschluss von Progesteronrezeptorexpression, HER2 und Ki-67 den Nodalstatus korrekt vorhersagen. Für die 200 Patientinnen, deren Risiko als besonders hoch vorhergesagt wurde, lag die Rate von richtig positiven Befunden bei 70%.Schlussfolgerung:Modelle, die sich lediglich auf tumorbiologische Faktoren des Primärtumors stützen, können unabhängig von klinischen Stagingparametern den axillären Lymphknotenstatus vorhersagen. Durch Erweiterung auf zusätzliche Faktoren ließe sich so ein Modell entwickeln, auf dessen Grundlage bei Frauen mit geringem Risiko für eine axilläre Metastasierung auf die axilläre Lymphonodektomie verzichtet werden könnte.

Maternal anxiety and its correlation with pain experience during chorion villus sampling and amniocentesis

Purpose Invasive prenatal diagnostic procedures, such as chorion villus sampling (CVS) and amniocentesis (AC), are routinely performed to exclude or diagnose fetal chromosomal abnormalities. The aim of this study was to investigate anxiety-dependent pain experience during CVS and AC and the potential factors that increase anxiety and pain levels. Patients and methods During a 2-year period, women undergoing invasive procedures in three specialist centers were asked to participate in the study. Anxiety was evaluated before the procedure using the Spielberger State-Trait-Anxiety-Inventory, and pain was evaluated directly after the procedure using a verbal rating scale. Results Among the women, 348/480 (73%) underwent AC, while 131/480 (27%) underwent CVS. There was a significant correlation between state and trait anxiety (p<0.0001). A positive correlation existed between the degree of anxiety and the level of pain experienced (p=0.01). There was a positive correlation for trait anxiety (p=0.0283) as well as for state anxiety (p=0.0001) and pain perception (p=0.0061) when invasive procedure was performed owing to abnormal ultrasound finding or to a history of fetal aneuploidy. Maternal age was found to be another influencing factor for the experienced pain (p=0.0016). Furthermore, the analysis showed a significant negative correlation between maternal age and anxiety. That applies for trait anxiety (p=0.0001) as well as for state anxiety (p=0.0001). The older the woman, the less anxious the reported feeling was in both groups. The main indication for undergoing CVS was abnormal ultrasound results (45%), and the main reason for undergoing AC was maternal age (58%). Conclusion Procedure-related pain intensity is highly dependent on the degree of anxiety before the invasive procedure. In addition, the indication has a significant impact on the emerging anxiety and consequential pain experiences. These influencing factors should therefore be considered during counseling and performance.

Pränatalmedizin. Pränatale Diagnostik von Chromosomenstörungen vor dem Hintergrund der aktuellen Gesetzgebung

Neue Screening-Tests zur Erkennung pranataler Aneuploidien drangen derzeit auf den Markt, ohne dass jedoch von den Vertreibern hinreichend auf gesetzliche Lucken und versicherungsrechtliche Fallstricke hingewiesen wird, die sich im Haftungsfall fur den niedergelassenen Frauenarzt ergeben konnen. Im Folgenden sollen die wichtigsten derzeit gultigen Gesetzesinhalte vorgestellt werden, die direkte Auswirkung auf die tagliche Arbeit in der Schwangerenvorsorge haben. Die Liste der angefuhrten Gesetze und Richtlinien ist nicht abschliesend, und es obliegt jedem Arzt, sich stets uber die aktuell geltenden Rechtsbestimmungen zu informieren.

Aneuploidy screening during pregnancy by a three-dimensional Advanced First Trimester Screening model: Description of the AFS-3D algorithm

A novel screening method for fetal aneuploidies was developed, in which nuchal translucency (NT), pregnancy‐associated plasma protein‐A (PAPP‐A), and free‐β human chorionic gonadotropin (free‐β hCG) are placed into a three‐dimensional scatter plot. Likelihood ratios are directly inferred from the ratio of already observed healthy and diseased fetuses. This method is called ‘Three‐dimensional Advanced First trimester Screening’ (AFS‐3D). It was aimed to develop and test a new algorithm based on the results of previous studies.