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Supplementary Data from Prognostic Effect of Epithelial Cell Adhesion Molecule Overexpression in Untreated Node-Negative Breast Cancer

Purpose: Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention not only as a prognostic factor in breast cancer but also as a potential target for immunotherapy. We examined Ep-CAM expression in 402 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting.Experimental Design: Ep-CAM expression was evaluated by immunostaining. Its prognostic effect was estimated relative to overexpression/amplification of HER-2, histologic grade, tumor size, age, and hormone receptor expression.Results: Ep-CAM status was positive in 106 (26.4%) patients. In multivariate analysis, Ep-CAM status was associated with disease-free survival independent of age, pT stage, histologic grade, estrogen receptor (ER), progesterone receptor (PR), as well as HER2 status (P = 0.028; hazard ratio, 1.60; 95% confidence interval, 1.05-2.44). Recently, so-called triple-negative (HER-2, ER, and PR) breast cancer has received increased attention. We noticed a similar association of Ep-CAM with disease-free survival in the triple-negative group as for the entire cohort.Conclusion: In this study of untreated breast cancer patients, Ep-CAM overexpression was associated with poor survival in the entire cohort and in the subgroup of triple-negative breast cancer. This suggests that Ep-CAM may be a well-suited target for specific therapies particularly in HER-2–, ER-, and PR-negative tumors.

Supplementary Table 4 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer

Supplementary Table 2 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer

Supplementary Tables 1, 3, 5-6, Figures 1-6 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer

Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motifs, we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified coregulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B-cell and T-cell infiltration. We calculated metagenes as a surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with principal component analysis. Distinct patterns led to the hypothesis of a prognostic role of the immune system in tumors with high expression of proliferation-associated genes. In multivariate Cox regression analysis, the proliferation metagene showed a significant association with metastasis-free survival of the whole discovery cohort [hazard ratio (HR), 2.20; 95% confidence interval (95% CI), 1.40–3.46]. The B-cell metagene showed additional independent prognostic information in carcinomas with high proliferative activity (HR, 0.66; 95% CI, 0.46–0.97). A prognostic influence of the B-cell metagene was independently confirmed by multivariate analysis in a first validation cohort enriched for high-grade tumors (n = 286; HR, 0.78; 95% CI, 0.62–0.98) and a second validation cohort enriched for younger patients (n = 302; HR, 0.83; 95% CI, 0.7–0.97). Thus, we could show in three cohorts of untreated, node-negative breast cancer patients that the humoral immune system plays a pivotal role in metastasis-free survival of carcinomas of the breast. [Cancer Res 2008;68(13):5405–13]

Purpose The aim was to develop and update a guideline which would improve the quality of care offered to women with gestational and non-gestational trophoblastic disease, a group of diseases characterized by their rarity and biological heterogeneity. Methods In accordance with the method used to compile S2k-guidelines, the guideline authors carried out a search of the literature (MEDLINE) for the period 1/2020 to 12/2021 and evaluated the recent literature. No key questions were formulated. No structured literature search with methodical evaluation and assessment of the level of evidence was carried out. The text of the precursor version of the guideline from 2019 was updated based on the most recent literature, and new statements and recommendations were drafted. Recommendations The updated guideline contains recommendations for the diagnosis and therapy of women with hydatidiform mole (partial and complete moles), gestational trophoblastic neoplasia after pregnancy or without prior pregnancy, persistent trophoblastic disease after molar pregnancy, invasive moles, choriocarcinoma, placental site nodules, placental site trophoblastic tumor, hyperplasia at the implantation site und epithelioid trophoblastic tumor. Separate chapters cover the determination and assessment of human chorionic gonadotropin (hCG), histopathological evaluation of specimens, and the appropriate molecular pathological and immunohistochemical diagnostic procedures. Separate chapters on immunotherapy, surgical therapy, multiple pregnancies with simultaneous trophoblastic disease, and pregnancy after trophoblastic disease were formulated, and the corresponding recommendations agreed upon.

Im April 2018 erschien die erste deutsche interdisziplinare S3-Leitlinie fur die Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom. Von der Deutschen Krebshilfe im Rahmen des Leitlinienprogramms Onkologie gefordert fanden sich unter der Federfuhrung der Deutschen Gesellschaft fur Gynakologie und Geburtshilfe und der Arbeitsgemeinschaft Gynakologische Onkologie in der Deutschen Krebsgesellschaft Mandatstrager von 34 Fachgesellschaften, Patientenvertreterinnen sowie 6 Experten zusammen. Der folgende Artikel skizziert die wichtigsten Ergebnisse der 4‑jahrigen Arbeit.

7536 Background: Chimeric antigen receptor T-cell therapy (CART) is approved for treatment of relapsed and refractory large B cell lymphoma (r/r LBCL), however eligibility for patients (pts) treated on clinical trials included normal kidney function (NKF). There is a gap in knowledge regarding the safety and efficacy of CART in pts with reduced kidney function (RKF), despite the prevalence of chronic kidney disease in lymphoma pts. Methods: This is a single-center retrospective analysis of adult pts with r/r LBCL who received CART between 2017-2021. RKF was defined as estimated glomerular filtration rate (GFR) of < 60 ml/min and NKF defined as GFR ≥ 60 ml/min, at time of lymphodepletion chemotherapy (LDC). Increased length of ICU stay define as > 3 days. Kaplan-Meier method used to estimate the time-to-event endpoints including progression free survival (PFS), and overall survival (OS). Results: We identified 210 pts who received CART, of those 169 (80.5%) had NKF and 41(19.5%) had RKF (15-59 ml/min, 27% < 45). Median age of pts was 60 and 63% of RKF pts were older than 60 vs 45% in NKF group (p = 0.03). Median Hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score of pts with RKF was higher than NKF (3 vs. 1, P = 0.004). Pts with RKF had significantly longer ICU length of stay (29.3% vs. 13.6%; p = 0.01). There was no difference in grade 3 hematological toxicity (82.9% vs. 84.5%, p = 0.80) or infection within 30 days of CART (51.2% vs. 37.9%, p = 0.11) between RKF and NKF pts, respectively. CART specific toxicity including grade and frequency of cytokine release syndrome and neurotoxicity was also not related to renal function. After a median follow-up of 22.9 months (95% CI: 21.1-25.6 months), there was no significant difference in PFS and OS when comparing pts with RKF vs. NKF; PFS at 1 year of 31% (19-50%) vs. 33% (26-41%), p = 0.97, and OS at 1 year was 47% (34-67%) vs. 44% (37-57%), p = 0.45, and respectively. However, pts with RKF had a significant increase in non-relapse mortality (NRM) at 3 months (19.5% vs. 8.3%, p = 0.03), and at 6 months (22% vs. 9.5%, p = 0.02), respectively. Conclusions: In this retrospective single center study we observed reassuring durable remission rates in pts with r/r LBCL and RKF who received CART, without significantly different PFS or OS. Interestingly our analysis found that increased ICU length of stay and higher rates of NRM early after CART were associated with RKF. While our data shows RKF does not preclude pts from receiving CART for r/r LBCL, it does suggest that patients with RKF may need closer monitoring and multidisciplinary management.

TPS7589 Background: Primary mediastinal large B-cell lymphoma (PMBL) is a rare and distinct subtype of diffuse large B-cell lymphoma and affects primarily young adults. PMBL has a unique genomic profile that has similarities to classic Hodgkin lymphoma with CD30 expression and genomic alterations in the programmed T-cell death-ligand 1 (PD-L1) locus 9p24.1. The trial CheckMate-436, including relapsed/refractory PMBL patients treated with nivolumab (antibody that binds to immune checkpoint PD-1) and brentuximab vedotin ((BV) anti-CD30 antibody-drug conjugate) showed an overall response rate (ORR) of 73% and complete response rate (CRR) of 43% (Zinzani et al. JCO 2019). Although most PMBL patients can be cured with frontline chemoimmunotherapy with or without radiotherapy, the outcome of patients having rr-PMBL treated with intensive regimens is generally unfavorable. The discovery of new frontline regimens to decrease chemoresistance and toxicities represents an urgent unmet clinical need for PMBL patients. Methods: We are conducting a phase II, open-label, single-center clinical trial combining BV-Nivolumab alone and then combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for patients with previously untreated PMBL Patients 18 years or older with previously untreated PMBL, stage I to stage IV disease are eligible. However, patients with an urgent need for cytoreductive treatment will be excluded. Patients will receive BV 1.8 mg/Kg IV and Nivolumab 240 mg flat dose IV day 1 for cycles 1 and 2, in a 21-day cycle. During cycles 3 and 4, R-CHP will be added to BV-Nivolumab. Patients who have achieved complete response (CR) at PET/CT before cycle 5 will receive 2 more cycles of BV-Nivolumab+R-CHP (cycle 5 and 6) and BV-Nivolumab only for cycles 7 and 8. In case of CR on PET/CT after cycle 8, therapy will be considered completed. Patients in PR on PET/CT before cycle 5 will receive 4 more cycles of BV-Nivolumab+R-CHP (cycles 5-8). The primary endpoint is CRR at the end of therapy (EOT). The maximum sample size for the PMBL cohort is 40 patients, with a target CRR at EOT of 70%. The null hypothesis is that the true CRR at EOT is 50%, and the alternative hypothesis is that the true CRR at EOT is 70%. The Simon’s optimal two-stage design controls the one-sided type I error rate at 0.06 and yields the power of 0.8. The secondary endpoints will include the response rate of BV-Nivolumab+R-CHP at the end of the immune lead-in, landmark survival outcomes, the safety of the combination, and patient-reported outcome. Exploratory analyses include assessing molecular response by sequencing cell-free DNA and Multiplexed ion beam imaging to analyze the tumor microenvironment. The trial is actively accruing at MD Anderson Cancer Center, and 2 out of 40 patients have been enrolled. Clinical trial information: NCT04745949.

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose Using evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal extent of surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy if required. An evidence-based optimal use of different therapeutic modalities should improve the survival rates and quality of life of these patients. This S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources included reviews of evidence, which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one part of the guideline. Identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then subsequently modified during structured consensus conferences and/or additionally amended online using the DELPHI method, with consent between members achieved online. The guideline report is freely available online. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of endometrial cancer including precancers and early endometrial cancer as well as recommendations on palliative medicine, psycho-oncology, rehabilitation, patient information and healthcare facilities to treat endometrial cancer. The management of precancers of early endometrial precancerous conditions including fertility-preserving strategies is presented. The concept used for surgical primary therapy of endometrial cancer is described. Radiotherapy and adjuvant medical therapy to treat endometrial cancer and uterine carcinosarcomas are described. Recommendations are given for the follow-up care of endometrial cancer, recurrence and metastasis. Palliative medicine, psycho-oncology including psychosocial care, and patient information and rehabilitation are presented. Finally, the care algorithm and quality assurance steps for the diagnosis, therapy and follow-up of patients with endometrial cancer are outlined.

Im April 2018 erschien die erste deutsche interdisziplinare S3-Leitlinie fur die Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom. Dieser Beitrag ist die Zusammenfassung des Kap. 4: „Diagnose, Fruherkennung, Bildgebung und Pathologie“ mit dem Ziel, dem Leser eine Kurzfassung an die Hand zu geben. Dargestellt sind die Empfehlungen zur Diagnose und Fruherkennung von Endometriumkarzinomen, ferner die Indikationen zur Bildergebung und die Anforderungen fur die pathologische Aufarbeitung.

Mit 11.000 Neuerkrankungen in Deutschland ist das Endometriumkarzinom das vierthaufigste Malignom der Frau. Ein guter Algorithmus in der Diagnostik hat einen besonderer Stellwert im Hinblick auf gute Vorbereitung und Planung der operativen Versorgung sowie in der Vermeidung unnotiger operativer Eingriffe. Dazu tragen auch die seit 2010 geltenden Modifikationen der Stadieneinteilung bei. Die Ubersichtsarbeit erfolgte auf der Basis einer selektiven Literaturrecherche. Postmenopausale und azyklische Blutungen mit oder ohne Vorliegen von Risikofaktoren sollten histopathologisch abgeklart werden. Fur ein Screening asymptomatischer Patientinnen gibt es derzeit kein sinnvolles Verfahren. Die diagnostische Hysteroskopie mit fraktionierter Abrasio stellt den Goldstandard in der Diagnostik dar. Verfahren zur Festlegung der Invasionstiefe leiden unter ihrer schlechten Sensitivitat und sind derzeit nicht Bestandteil der praoperativen Routine. Die Klassifikation des Endometriumkarzinoms ergibt sich gemas dem chirurgisch-operativ erhobenen Befund. Die aktuellen Modifikationen fuhren zu einer besseren Einteilung und ermoglichen eine sinnvollere Zuordnung zu einzelnen Therapieoptionen. Die Schnittbildverfahren zeichnen sich durch eine sehr gute Spezifitat aus, zeigen aber durchweg eine schwache Sensitivitat.

Die Lymphknotenoperation gehort zum etablierten Standard der Karzinomchirurgie auch in gynakologischen Onkologie. Bereits seit einigen Jahren wird jedoch intensiv diskutiert, in welchem Umfang dieses Vorgehen noch zeitgemas ist [1], insbesondere im Hinblick auf den therapeutischen Effekt jenseits der Informationen zur Tumorausbreitung. Die vorliegende Ubersicht fasst den derzeitigen Stand zur Lymphadenektomie fur die gynakologische Onkologie zusammen.

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose The use of evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy where required. The evidence-based optimal use of different therapeutic modalities should improve survival rates and the quality of life of these patients. The S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources include reviews of evidence which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one area of the guideline. The identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then modified during structured consensus conferences and/or additionally amended online using the DELPHI method with consent being reached online. The guideline report is freely available online. Recommendations Part 1 of this short version of the guideline presents recommendations on epidemiology, screening, diagnosis and hereditary factors, The epidemiology of endometrial cancer and the risk factors for developing endomentrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer including the pathology of the cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer.

In 2013, 2009 and 2006, the Arbeitsgemeinschaft Gynakologische Onkologie evaluated the therapeutic approaches for endometrial carcinoma and the adherence to their guideline in Germany. Here, the adjuvant treatment decisions were presented. A questionnaire was developed and sent to all 682 German gynecological departments in 2013 (775 in 2009 and 500 in 2006, respectively). The results of the questionnaires were compared with the recommendations of the guideline and with each other using Fisher’s exact test. Responses were available in 40.0 % in 2013, 33.3 % in 2009 and 35.8 % in 2006. Participants recommended external beam radiotherapy (EBRT) in 13 out of 16 requested stages and vaginal brachytherapy (VBT) in only 10 out of 16 requested stages as suggested by the guideline. Comparing the results of 2013 with 2009, less participants used EBRT and VBT in 7 out of 16 and in 6 out of 16 requested stages, respectively. Conversely, more participants offered adjuvant chemotherapy (CT) in 2013 (90.4 %) compared to 61.9 % in 2009 (p

In 2013, 2009, and 2006, the Arbeitsgemeinschaft Gynäkologische Onkologie evaluated the therapeutic approaches and the adherence to their guidelines for endometrial carcinoma (EC) in Germany. Here, we present the results concerning the surgical procedures.A questionnaire was developed and sent to 682 German gynecological departments in 2013 (775 in 2009 and 500 in 2006). The results were compared with the recommendations of the guideline and with each other.Responses were available in 40.0 % in 2013, 33.3 % in 2009, and 35.8 % in 2006, respectively. Pelvic lymphadenectomy (LAN) was performed in accordance with the guidelines with some exceptions in 2013, 2009, and 2006, whereas paraaortic LAN was performed in accordance with the guideline only in 2009. Histological high-risk subtypes of EC received pelvic and paraaortic LAN in 2013, 2009, and 2006 in accordance with the guidelines with small exceptions. LAN for Patients, who were postoperatively upstaged or upgraded, was not conducted in accordance with the guidelines in 2013, 2009, and 2006. In 2013, 84.6 % of the participants offered the laparoscopic approach (LSA) for hysterectomy and bilateral salpingo-oophorectomy, 63.3 % for pelvic LAN, and 49.1 % for paraaortic LAN, respectively. More participants offered the LSA in 2013 compared to 2009 and 2006 (p values0.014).The paraaortic LAN, the LSA as well as the second operation on patients who had postoperatively been upstaged were not conducted in accordance with the guideline [CORRECTED]. Improvements concerning surgical treatment are possible and might lead to higher survival rates and a reduction of morbidity in patients with EC in Germany.

Outcomes for youth from foster care have been found to be poor. The education and employment outcomes of youth and alumni of foster care served by transition programmes located in five major US cities were examined. Data were collected by case managers and reported to evaluators quarterly on 1058 youth from foster care for over 2 years. Job preparation, transportation, child care, education support services and life skills were the most common services provided to youth. During the 2-year study period, 35% of participants obtained employment, 23% obtained a General Education Development or diploma, and 17% enrolled in post-secondary education. It was found that the longer the youth were enrolled, the more education and employment outcomes they achieved. Further, job preparation and income support services were associated significantly with achieving any positive education or employment outcome. Results indicated that certain services provided over an extended period of time can improve outcomes for youth placed in foster care. For youth to achieve positive outcomes as they transition to adulthood, additional services are necessary. Other implications are discussed.

ObjectiveIn 2009 and 2006, the Arbeitsgemeinschaft Gynäkologische Onkologie evaluated therapeutic approaches for endometrial carcinoma (EC) in Germany.Methods and MaterialsA questionnaire was developed and sent to 775 German gynecologic departments in 2009 (500 in 2006). The results of the questionnaires were compared with each other and with the recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie’s guideline. Subgroup analyses were performed, dividing the participating centers into small and large centers and into centers with less and more experience with EC.ResultsResponses were available in 33.3% in 2009 and 35.8% in 2006. Comparing 2009 with 2006, it became apparent that peritoneal washing cytology was performed in 94.6% versus 86.9% (P= 0.008), pelvic lymphadenectomy (LAN) in 98.3% versus 95.3%, and paraaortic LAN in 90.2% versus 73.8% (P< 0.001) for endometrioid EC, and LAN for histologic high-risk subtypes of EC in 99.6% versus 94.2% (P= 0.001), respectively. In 2009, all these criteria met the recommendation of the guidelines. Reoperation for LAN after postoperative upstaging was performed in 66.1% versus 50.6% (P= 0.002), and adjuvant systemic treatment with chemotherapy and endocrine therapy was performed in 63.7% versus 48.8% (P= 0.003) and 25.7% versus 15.4% (P= 0.014), respectively. This showed nonadherence to the guidelines. Laparoscopic approach was performed in 30.4% versus 19.7% (P= 0.014) of the participating centers, respectively. In subgroup analysis, laparoscopic approach showed a significant difference between small centers (11.5%) and large centers (27.3%) in 2006 (P= 0.012).ConclusionsGerman hospitals increasingly follow the guidelines concerning LAN and peritoneal washing cytology. However, recommendations concerning reoperating in upstaged patients and adjuvant treatment decisions do not meet the guidelines, thus underlining great uncertainties in this field of gynecologic oncology.

Objective P53 tumor suppressor gene plays a role in endometrial carcinogenesis. Former studies described correlations between p53 protein overexpression in endometrial cancer and prognostic factors, measured by immunohistochemistry. But data is still controversial. The aim of this study was to measure p53 and phospho-p53 overexpression by Western blot and evaluate correlations between overexpression and prognostic and clinical factors. Phospho-p53 seems to be the functional p53 protein and was examined for the first time in endometrial cancer. Methods 40 patients with endometrial cancer were included in the study. A control group of 20 patients with normal endometrial tissue samples was used. Western blot was performed for detection of p53 and phospho-p53. Clinical and pathological parameters were obtained from medical records. Statistical analysis was performed using the log-rank test, the Mann–Whitney test for two independent groups and the Fisher's exact test for dichotomous groupings. Results In 17.5% of the patients with endometrial cancer a p53 overexpression could be evaluated. There was a correlation between a p53 overexpression and recurring disease (p: 0.014), a negative progesterone receptor status (p: 0.021) and a low BMI (p: 0.022). Only one of 40 patients had a phospho-p53 expression. Conclusion Western blot is a valid method for the detection of p53 overexpression. As other authors described before, p53 overexpression seems to correlate with negative prognostic factors. The correlation between p53 overexpression and a low BMI may underline the relationship between p53 alterations and biological aggressive endometrial carcinomas.

Metastasis from primary tumors remains a major problem for tumor therapy. In the search for markers of metastasis and more effective therapies, the tumor metabolome is relevant because of its importance to the malignant phenotype and metastatic capacity of tumor cells. Altered choline metabolism is a hallmark of cancer. More specifically, a decreased glycerophosphocholine (GPC) to phosphocholine (PC) ratio was reported in breast, ovarian, and prostate cancers. Improved strategies to exploit this altered choline metabolism are therefore required. However, the critical enzyme cleaving GPC to produce choline, the initial step in the pathway controlling the GPC/PC ratio, remained unknown. In the present work, we have identified the enzyme, here named EDI3 (endometrial differential 3). Purified recombinant EDI3 protein cleaves GPC to form glycerol-3-phosphate and choline. Silencing EDI3 in MCF-7 cells decreased this enzymatic activity, increased the intracellular GPC/PC ratio, and decreased downstream lipid metabolites. Downregulating EDI3 activity inhibited cell migration via disruption of the PKCα signaling pathway, with stable overexpression of EDI3 showing the opposite effect. EDI3 was originally identified in our screening study comparing mRNA levels in metastasizing and nonmetastasizing endometrial carcinomas. Both Kaplan–Meier and multivariate analyses revealed a negative association between high EDI3 expression and relapse-free survival time in both endometrial ( P < 0.001) and ovarian ( P = 0.029) cancers. Overall, we have identified EDI3, a key enzyme controlling GPC and choline metabolism. Because inhibition of EDI3 activity corrects the GPC/PC ratio and decreases the migration capacity of tumor cells, it represents a possible target for therapeutic intervention.

The public discussion about health care financing has an enormous relevance for the field of gynaecology and obstetrics. This second part of the paper of the financing commission of the DGGG presents essential financial aspects and problems, influencing our speciality. Among other aspects, the inputs of the DRG system are discussed for our field. The representation of all levels of care and all German states in the InEK calculation system is still a problem. Regarding the inpatient care, the number of cases has decreased by 23 over the last years due to the shift to the outpatient setting. Surgeries in the outpatient setting have increased by 31.5 from the year 2004 to the year 2008 (all specialities). Moreover, a decrease of obstetric cases by 5.7 and cases directly associated with birth by 7.3 has to be mentioned. Altogether, our field has lost 6.8 of all inpatient cases over the last years. The economic pressure is still high and it is difficult to maintain cost recovery. Regarding the personal resources, legal demands are problematic for perinatal centres, e. g. loss of the on-call duty possibility, availability of medical specialist expertise and necessity of permanent standby service of the head of the perinatal centre. Further problems of the inpatient setting concern the field of urogynaecology (lack of young academics, new technical procedures with lack of data, missing representation of complex surgeries and lack of reimbursement in case of surgeries in the outpatient setting) and the benign and malign gynaecological surgery. While standard procedures are almost represented in the DRG system, there is still a high demand for development of appropriate reimbursement for complex and infrequent case constellations, interdisciplinary procedures and simultaneous multiplex surgeries. The collaboration of all colleagues is essential.

Purpose: Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention not only as a prognostic factor in breast cancer but also as a potential target for immunotherapy. We examined Ep-CAM expression in 402 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. Experimental Design: Ep-CAM expression was evaluated by immunostaining. Its prognostic effect was estimated relative to overexpression/amplification of HER-2, histologic grade, tumor size, age, and hormone receptor expression. Results: Ep-CAM status was positive in 106 (26.4%) patients. In multivariate analysis, Ep-CAM status was associated with disease-free survival independent of age, pT stage, histologic grade, estrogen receptor (ER), progesterone receptor (PR), as well as HER2 status (P = 0.028; hazard ratio, 1.60; 95% confidence interval, 1.05-2.44). Recently, so-called triple-negative (HER-2, ER, and PR) breast cancer has received increased attention. We noticed a similar association of Ep-CAM with disease-free survival in the triple-negative group as for the entire cohort. Conclusion: In this study of untreated breast cancer patients, Ep-CAM overexpression was associated with poor survival in the entire cohort and in the subgroup of triple-negative breast cancer. This suggests that Ep-CAM may be a well-suited target for specific therapies particularly in HER-2–, ER-, and PR-negative tumors.

Background. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) contribute to the invasiveness of many carcinomas. Here, we studied a possible association between cytosolic uPA and PA-1 concentrations in tumor tissue with prognosis in patients with endometrial cancer. Methods. Cytosolic concentrations of uPA and PAI-1 were determined in 69 primary endothelial adenocarcinomas using an enzyme-linked immunoassay (ELISA). A possible influence of uPA and PAI-1 was studied by multivariate Cox regression adjusting for the established clinical prognostic factors FIGO-stage, grading, depth of invasion, diabetes mellitus and age. Results. Both uPA ( p =0.011) and PAI-1 ( p =0.003) were associated with relapse free time using the multivariate proportional hazards model. Association with overall survival was less pronounced with p =0.021 for uPA and p =0.358 for PAI-1. Concentrations of PAI-1 increased with FIGO stage ( p =0.003) and with histological grading ( p =0.005). Both uPA and PAI-1 concentrations were negatively correlated with estrogen and progesterone receptor levels. Conclusion. The combination of high cytosolic concentrations of uPA (>5 ng/mg total protein) and high PAI-1 (>20 ng/mg total protein) may reveal a group of patients with increased risk of progression.

Objective The results obtained using plastic surgery reconstruction in 207 patients with a primary or recurrent vulvar carcinoma were analyzed with regard to the surgical procedures applied, pre-treatment and post-operative findings, along with the long-term oncological disease course. Study design Standardized data concerning the surgical procedures applied and clinical factors were collected in a databank and statistically analyzed. Results The flaps employed were termed either ‘local' (cutaneous or fasciocutaneous; n =84) or ‘regional' (myocutaneous, n =123). For local flaps, the rate of secondary healing was 31%, dropping to 20% for regional flaps. Such healing disturbances often affected the donor region and did not lead to lasting clinical problems such as stenosis or distortion. Severe disturbances of wound healing (loss of more than 10%) were not observed in local flaps, whereas such problems were encountered in 5.9% of regional flaps. Gluteal thigh flaps were most frequently applied and were also the most successful type of myocutaneous reconstruction. Therapy was selected on an individual basis according to tumor status. Conclusion Plastic surgery reconstruction broadens the range of operative therapies available for the treatment of vulvar carcinomas, especially those at an advanced stage or recurrent tumors, and leads to a favorable oncological disease course as well as improved cosmetic results.

Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) mRNA expression was also determined by quantitative RT-PCR. We observed a clear association of the PR status with chemosensitivity to paclitaxel. Higher levels of immunohistochemically detected PR expression correlated with decreased chemosensitivity (P=0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P=0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P=0.013). Multiple regression analysis identified PR receptor status and T-stage as independent predictors of paclitaxel chemosensitivity, whereas the ER, N-stage, grading and age were not influential. In conclusion, in vitro sensitivity to paclitaxel was higher for PR-negative compared with PR-positive breast carcinoma cells. Thus, PR status should be considered as a possible factor of influence when designing new trials and chemotherapy protocols.

PURPOSE This study describes the results of the plastic reconstructive measures in 207 patients with a primary or a recurrent vulvar cancer. These procedures were analysed in sight of surgical excision, previous therapy, and detailed postoperative results. METHODS All procedures and clinical parameters were recorded standardized in a data bank and analysed using statistical methods. RESULTS In 123 local (cutaneous or fasciocutaneous) and 84 regional (myocutaneous) flaps we found a primary healing in about 2/3 of the cases. Local flaps exhibited secondary healing in 31 %, regional flaps in 20 %. This often involved the donor sites and generally did not present any permanent problems. Pronounced healing disturbances (necrosis of more than 10 %) was not achieved in local flaps, in regional flaps it aroused in 5.9 %. Gluteal femoral flaps were used most frequently and showing the best results of all myocutaneous flaps. They were comparable with the local reconstructions by a high degree of reliability and healing. In 15 cases a tissue-loss was observed. In these patients, elevated risk factors, certain oncological characteristics and technical problems could be demonstrated. CONCLUSION Plastic surgery enlarges the spectrum of operative therapy of vulvar cancer, especially in extensive or recurrent tumors, leading to a favourable oncological outcome and good cosmetic results. Severe healing disturbances are rare and can be controlled.

Purpose: Human papillomavirus (HPV)16 E6 and E7 oncoproteins that are required for cellular transformation represent candidate targets for HPV specific and major histocompatibility complex (MHC) class-I restricted CD8+ T-cell responses in patients with cervical cancer. In the present study, we identified HPV specific T-cells in different biological compartments (peripheral blood lymphocytes [PBL], tumor tissue, tumor-draining lymphnodes) using MHC-class I tetramers containing an appropriate HPV 16 E7 peptide. Material and Methods: FACS sorted (fluorescence activated cell sorting) CD8+T-cells isolated from healthy blood donors (n=10), patients with carcinoma in situ (n = 9) and invasive cervical cancer (n = 15) were obtained from PBL, tumor and pelvic nodes and evaluated for the presence of HPV 16 E7 specific effector CD3 + lymphocytes using the new tetramer technology. HPV DNA in tumor tissue was detected by PCR. All cervical cancer lesions could be identified as HPV 16 positive. PBL, tumor infiltrating lymphocytes (TIL), or T-cells from tumor-draining lymph nodes were isolated, gated on CD3 + CD8+T-cells as indicated and tested for the frequency of HPV 16 E7 using HLA-A2 tetramer complexes. All patients included showed an HLA-A2 haplotype. Results: 50% of healthy individuals, but less than 20% of patients (cervical intraepithelial neoplasia (CIN), invasive cancer) showed a specific cytotoxic CD8 + immune response to a defined HPV 16 E7 11-19 epitope (YMLDLQPET) in peripheral blood. HPV-reactive cytotoxic T-cells were detectable in tumor-draining lymph nodes in only one patient. Conclusions: The tetramer-sorting of CD8 + T-cells from different biological compartments in patients with HPV associated cancer lesions permits the determination of the target specificity of CD8 + effector T-cells without further need for in vitro manipulation. Furthermore, this new method helps to define the most appropriate target epitopes for novel vaccine designs.

In addition to the loss of function, mutant p53 can possess a dominant-negative effect on wild-type p53 and may also exert gain-of-function activity. It is not clear whether the functional status of p53 mutation contributes to differences in outcome in endometrial cancer. We collected a total of 92 RNA samples of high quality from endometrial cancer tissues, and the samples were subjected to yeast functional assay and sequencing for p53 mutations. The detected mutant p53 genes were further investigated for their dominant-negative activity using a yeast-based transdominance assay. p53 mutation was found in 24 out of 92 (26.1%) tumors, of which 10 exhibited no dominant-negative activity (recessive mutation) and 14 showed dominant-negative activity. Dominant-negative p53 mutation was related to advanced stages (p = 0.01), nonendometrioid type tumors (p = 0.01) and grade 3 tumors (p = 0.04). The patients with dominant-negative mutation had significantly shorter survival than patients with no mutation (p < 0.0001) and those with a recessive mutation (p = 0.01) in the p53 gene. No difference in survival was found between the patients with tumors harboring a recessive p53 mutation and those with tumors harboring a wild-type p53. Multivariate analysis revealed that dominant-negative p53 mutation (p = 0.019), FIGO stage (p = 0.0037) and histologic subtype (p = 0.014) were independently related to patient survival. Dominant-negative p53 mutation was the most important prognostic factor for stage III/IV endometrial cancer (p = 0.0023). In conclusion, dominant-negative p53 mutation is often found in advanced stages and aggressive histologic subtypes of endometrial cancer and it is a strong predictor of survival of patients with advanced endometrial cancer. To elucidate further the role of p53 mutation in endometrial cancer, it is necessary to investigate gain-of-function activity involving dominant-negative p53 mutant proteins. © 2005 Wiley-Liss, Inc.

Objective: To evaluate the impact of treatment for genital cancer on quality of life and body image to determine patients' therapy-related needs with respect to qualitative improvements of medical care before and after surgery. Methods: Between June 1993 and July 2003 129 women with cervical cancer were assessed before and 4 and 12 months after surgery by semistructured interviews and standardised questionnaires. Thanks to funding, since 1999 all patients with a diagnosis of genital or breast cancer can participate in this prospective study. In this paper we will focus on therapy-related changes in quality of life and body image in women with cervical cancer. The evaluation of quality of life (CARES) incorporated five aspects: physical and psychosocial health; marital and sexual status; medical interaction. With respect to body image (Strauss and Appelt) the attractiveness/self-confidence and sexual uncertainty were evaluated. Results: Before surgery, women with a Wertheim's procedure had significantly less problems with regard to the quality of life global score (p = 0.002) and several subscales compared to women with a pelvic exenteration. After surgery, both groups indicated that sexual problems were the greatest limitation in terms of quality of life, especially in women with non-reconstructive surgery as well as in women with adjuvant radio- and/or chemotherapy. With respect to body image, attractiveness/self-confidence was significantly reduced postoperatively compared to the preoperative status in both groups (p = 0.000), and also worsened with the extent of treatment. Conclusion: This on-going study demonstrates the interrelationship between the treatment and the patient's quality of life, especially with regard to sexuality and body image. Our results suggest not only providing reconstructive surgery if possible, but also integrating psychosocial information on future quality of life before surgery as well as offering psychosocial support related to the extent of treatment after surgery.

Fragestellung: Das geplante Mammographiescreening wird eine grosere Zahl unklarer Mammographiebefunde hervorrufen, in Zukunft wird daher die Zahl der Mammabiopsien zunehmen. Mit der stereotaktischen vakuum-assistierten Mammabiopsie steht ein Verfahren zur Verfugung, welches eine patientenschonende Moglichkeit der Abklarung verspricht. Ziel der vorliegenden Untersuchung war es, die klinischen Ergebnisse dieser Methode zu uberprufen.Material und Methode: 166 vakuum-assistierte Mammabiopsien wurden mit einem standardisierten Untersuchungsprotokoll durchgefuhrt und ausgewertet.Ergebnisse: Die histopathologische Aufarbeitung zeigte in 75,8 % gutartige Befunde. Lasionen mit Risikocharakter und nichtinvasive Neoplasien wurden in 18,6 % diagnostiziert, invasive Karzinome fanden sich bei 9 Biopsien (5,4 %). Die Komplikationsrate war insgesamt sehr gering. Weder Haut- noch Thoraxwandverletzungen, noch Schmerzhaftigkeit oder intraoperative Blutungen fuhrten zu einem Abbruch. Postinterventionell fanden sich vier Nachblutungen, im weiteren Verlauf in 28,3 % oberflachliche, in 3 % ausgedehnte Hauthamatome, alle ohne die Notwendigkeit einer operativen Revision. Des Weiteren sahen wir in keinem Fall eine Infektion. Im Durchschnitt wurden 17,2 (8-31) Gewebezylinder gewonnen. Nach Entnahme von 18 Zylindern stand in allen Fallen der endgultige histopathologische Befund fest, desgleichen war in allen Fallen der Mikrokalk getroffen. Die underestimation-rate betrug drei von funfunddreisig Fallen.Schlussfolgerungen: Die vorliegende klinische Studie zeigt, dass die stereotaktische Vakuumbiopsie ein sehr zuverlassiges Verfahren zur Abklarung unklarer Mammabefunde darstellt, welches deutlich geringere Komplikationsraten als eine konventionelle Biopsie aufweist. Objective: Screening mammography (as planned in germany) will lead to an increasing number of breast biopsies. The purpose of this study was to determine the promise of directional large core biopsy as a patient-protecting therapeutic method.Material and methods: 166 vacuum assisted, X-ray-guided biopsy procedures were analysed.Results: Histopathologic examination resulted in 75.8 % benign lesions. Atypical proliferation and noninvasive neoplasia was found in 18.6 %, invasive carcinoma in 5.4 % of the biopsies. Complications were few. Neither skin- or chestwall injuries, nor pain or intraoperative bleeding caused an abortion. Postoperative we found four cases of bleeding, further on in 28.3 % a superficial, in 3 % a larger and deep hematoma, but in total without any operative revision. No infection was diagnosed. In the average 17.2 (8-31) specimens were removed. After excision of 18 probes the definitive histopathologic diagnosis was clear in all cases, also, the microcalcifications were found. The underestimation rate amounted to 3 of 35 cases.Conclusions: This clinical study proves stereotactic vacuum-assisted biopsy as a relieable method for analysing indeterminate mammographically detected breast lesions, which shows lower rates of complications than conventional surgical procedures.

The aim of this study was to evaluate the biologic outcome of endometrial carcinomas as compared to clinical and pathologic parameters and to identify multivariate independent prognostic factors. Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence, and survival were collected. chi2 test was used to test association between variables. Kaplan-Maier method was used for survival analysis and Cox proportional hazards model for multiple regression analysis. Univariate analysis revealed that FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, age, additional diabetes mellitus, lymph node metastasis, and type of tumor were significantly associated with the overall-survival. For disease-free interval, FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, lymph node metastasis, and type of tumor were also significantly associated. Multivariate analysis revealed that FIGO stage, tumor grading, tumor type, depth of myometrial invasion, and biochemically measured progesterone receptor status were associated significantly with overall survival. A significant correlation as independent prognostic factors were also seen for recurrence free interval for FIGO stage, tumor grade, and biochemical progesterone receptor status. In multivariate statistical analysis we identified FIGO stage, tumor type, tumor grade, biochemical analysis of progesterone receptor status, and depth of myometrial invasion as independent prognostic factors for overall survival, and FIGO stage, biochemical analysis of progesterone receptor status, and tumor grade as independent prognostic factors for recurrence-free interval.

Objective In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+CD45RA+CD28+T-cells undergo clonal expansion and differentiate into CD8+CD45RO+ memory T-cells. Upon re- encounter with the nominal antigen, CD45RO+ T-cells are able to convert to CD8+CD45RA+CD28-T-cells displaying potent immune effector functions, including TNF-alpha production. This T-cell subpopulation constitutes a minor population in healthy individuals. In the present study we are currently evaluating whether this particular T-cell subset in PBL represents CD8+T-cells which may be able to recognize cervical cancer associated antigens provided by HPV 16 E7. Material and methods Flow-cytometric cell sorted CD8+CD45RA+CD28- and CD8+CD45RA+CD28-T-cells were obtained from patients with cervical cancer and tested for recognition of HLA-A2 restricted peptides derived from the human papillomavirus (HPV)16-E7 gene product using ELISA. HPV DNA in tumor tissue was detected by PCR. Results We show that the effector CD8+CD45RA+CD28-T-cell subset is expanded in peripheral blood lymphocytes (PBL) from patients with cervical cancer, but also in PBL from patients with an acute mycobacterial infection. CD8+T-cells from 3/6 cancer patients showed a peptide-specific immune response which could be segregated in peptide epitopes which elicited either a strong TNF-alpha production, or GM-CSF and IL-2 secretion. Peptide-reactivity could exclusively be detected in the ex vivo freshly isolated CD8+CD45RA+CD28-T-cell population. A similar situation was found to be true for HLA-A2 presented peptide epitopes derived from M. tuberculosis-associated antigens presented to T-cells obtained from patients with tuberculosis. Conclusions The sorting of CD8+CD45RA+CD28-T-cells enables to determine the fine specificity of CD8+ effector T-cells without the need for in vitro manipulation and aids to define the most appropriate target epitopes for novel vaccine designs.

Objective: We compared immunohistological examination of endometrium biopsy specimen with the results of the immunohistological examination of tumor specimen to analyse the valence of this preoperative examination according to the clinico-pathological findings and overall-survival. Material and Method: Between 1985 and 1995 193 women were treated of an endometrial carcinoma at the University hospital Mainz. In this group we evaluated 41 patients with enough preoperative endometrial biopsy material for a retrospective immunohistochemical analysis and complete follow-up data. The materials from diagnostic curettage were stained and analysed for oestrogen and progesterone receptor status and for MiB-1. The results were statistically analysed using Logrank-test for overall survival. Results. The mean follow-up time was 49 months. We found a significant correlation between staining results of oestrogen (p-value = 0.0005) and progesterone (p-value = 0.0003) receptor status with overall survival as well as for MiB-1 (p-value = 0.05). The correlation of staining results between biopsy specimen results and tumor material from hysterectomy was 84- 85 %. Conclusion: These well known prognostic factors are measurable on biopsy specimen material in same quality and high valence as on hysterectomy material.

Objective: We evaluated whether recurrence of intrauterine growth restriction (IUGR) in subsequent pregnancies can be predicted by histologic findings in the placenta. Methods: A total of 15,863 singleton deliveries were reviewed. A total of 32 cases of recurrent IUGR were identified. We reviewed the clinical data and the results of histomorphologic examination of the placentas in 61 mothers with 1 pregnancy complicated by IUGR, the 32 mothers with recurrent pregnancies complicated by IUGR, and 130 mothers with uncomplicated pregnancies. Maternal age > 35 years, coincidental social factors, and structural changes of the placental villi were analyzed as possible predictive factors. Results: Maternal age > 35 years, smoking, maternal diabetes or hypertension, and hypovascularization of the placenta (13% in the mothers with one pregnancy with IUGR, 28% in the mothers with recurrent IUGR and none in the control group) were risk factors for the recurrence of IUGR. Conclusion: Hypovascularization of the placental villi is an independent risk factor for recurrent IUGR in a subsequent pregnancy.

It is generally accepted that local growth of solid tumors and their ability to establish distant metastases are dependent on the formation of new blood vessels arising from preexisting ones (angiogenesis). The angiogenic response of the host is mediated by angiogenic molecules that are released from cancer and normal stroma cells, especially fibroblasts. The goal of the present study was to quantitatively compare the expression of the two most important angiogenic growth factors (VEGF, angiogenin) of cervical cancer cells (HeLa and Me-180) with that of cervical cancer-derived fibroblasts (from one tumor/patient) under defined normoxic and hypoxic conditions in vitro. The growth kinetics of cervical cancer cells (HeLa and Me-180) and tumor-derived fibroblasts were evaluated in vitro under normoxic and hypoxic conditions. Growth factor concentrations in the cell culture medium were measured by ELISA and the secretion rates per cell were calculated. Under normoxic conditions, both the cervical cancer cells as well as the tumor-derived fibroblasts released VEGF and angiogenin. The secretion rate of both angiogenic factors was significantly higher in the stroma cells than in the tumor cells (P0.05). VEGF and angiogenin secretion is significantly higher in the stroma cells under hypoxia than in the tumor cells investigated (P0.05). The presented data support the concept that in cervical cancer non-neoplastic fibroblasts could play a pivotal role in the complex process of tumor angiogenesis.

Objective: The purposes of this study were to analyze the relationship between clinical and pathological risk factors in endometrial cancer and additional diabetes mellitus and to clarify the correlation between additional diabetes mellitus and survival of patients with this disease. - Material and methods: This analyze included 181 patients with endometrial carcinoma who were treated between 1985 and 1995 at the University hospital Mainz. Patients with sarcoma were excluded. For statistical analysis a Χ 2 -test was performed for univariat analysis. A Kaplan-Meier procedure was performed for over all survival and disease free interval and COX-Regression for multivariate analysis of independence. - Results: The mean follow-up period was 49 months. The mean age was 65 years. 21.8% of the patients had an additional diabetes mellitus. These patients had a significantly deeper infiltration of the Myometrium (p-value = 0.004) and were more likely to have lymphonode metastasis (p-value = 0.02). - Conclusion: Our results show a correlation between Diabetes mellitus and adverse prognostic factors witch affects by the rate of lymphonode spread and overall survival.

Objective: Nitroglycerin was used successfully in the second-line treatment of severe hypertension in two pregnant patients. Case report: One patient with preexisting hypertension developed severe hypertension at 27 weeks' gestation. Treatment with dihydralazine and methyldopa caused toxic liver damage. Another patient had severe hypertension unresponsive to dihydralazine an also had uterine contractions. Both patients received intravenous nitroglycerin at a rate of 0.5-4.0 mg/h over a period of 3 days. Maternal mean blood pressure returned to an almost normal level and uterine contractions ceased. There were no negative effects on mother or fetus. Conclusion: Nitroglycerin may be considered for short-term second-line treatment of severe hypertension in pregnancy.

Falls die Schwangere nicht explizit ein Arztgesprach wunscht, kann die Anmeldung allein mit der Hebamme durchgefuhrt werden.