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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.

Soluble Fms-like tyrosine kinase-1 (sFlt-1) is thought to be causative in the pathogenesis of preeclampsia (PE) and specific removal of sFlt-1 via dextran sulfate cellulose (DSC)-apheresis was suggested as cure to allow prolongation of pregnancy in preterm PE. However, in addition a deranged lipoprotein metabolism may impact endothelial and placental function in PE. Lipoprotein-apheresis by heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) was previously applied and has been shown to alleviate symptoms in PE. This clinical trial reevaluates the clinical efficacy of H.E.L.P.-apheresis in PE considering sFlt-1.Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30-41 years) with very preterm PE (24+4 to 27+0 gestational weeks (GW)) (NCT01967355) compared to a historic control-group matched for GW at admission (28 GW; n = 6). Clinical outcome of mothers and babies, and pre- and post H.E.L.P.-apheresis levels of sFlt-1 and PlGF were monitored.In apheresis patients (2-6 treatments), average time from admission to birth was 15.0 days (6.3 days in controls; p = 0.027). Lung maturation was induced in all treated cases, and all children were released in healthy condition. Apheresis reduced triglycerides and LDL-cholesterol by more than 40%. Although H.E.L.P.-apheresis induced a transient peak baseline levels did not change and rather stabilized sFlt-1 levels at pre-apheresis levels throughout treatments, with sFlt-1/PLGF ratio remaining unaffected.H.E.L.P.-apheresis proved again to be safe and prolongs pregnancies in PE. However, without changing sFlt-1 levels below baseline lowering lipids or other yet undefined factors appear to be of more relevance than reducing sFlt-1.

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.

Objective Soluble Fms-like tyrosine kinase-1 (sFlt-1) is thought to be causative in the pathogenesis of preeclampsia (PE) and specific removal of sFlt-1 via dextran sulfate cellulose (DSC)-apheresis was suggested as a cure to allow for prolongation of pregnancy in preterm PE. However, in addition a deranged lipoprotein metabolism may impact endothelial and placental function in PE. Lipoprotein-apheresis by heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) was previously applied and has been shown to alleviate symptoms in PE. This clinical trial reevaluates the clinical efficacy of H.E.L.P.-apheresis in PE considering sFlt-1. Methods Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30–41 years) with very preterm PE (24 + 4 to 27 + 0 gestational weeks (GW)) (NCT01967355) compared to a historic control-group matched for GW at admission. Clinical outcome of mothers and babies, and pre- and post H.E.L.P.-apheresis levels of sFlt-1and PlGF were monitored. Results In apheresis patients (2–6 treatments), average time from admission to birth was 15.0 days (6.3 days in controls; p = 0.027). Lung maturation was induced in all treated cases, and all children were released in healthy condition. Apheresis reduced triglycerides and LDL-cholesterol by more than 40%. Although H.E.L.P.-apheresis induced a transient peak, baseline levels did not change and rather stabilized sFlt-1 levels at pre-apheresis levels Discussion Lipoprotein-apheresis proved again to be safe and prolongs pregnancies in PE. However, without changing sFlt-1 levels below baseline lowering lipids or other yet undefined factors appear to be of more relevance than reducing sFlt-1.

The increasing number of pregnant breast cancer patients calls for a therapy that is as efficient as possible. After 10 years of collecting data on pregnant breast cancer patients in the German Breast Group (GBG), proposals for diagnostic measures and therapy regarding this special situation have been developed on the basis of 500 observed cases. Chemotherapy is regarded as safe from the 14(th) week of gestation on, but it is strongly advised not to use trastuzumab. Adverse outcomes for the newborn were predominantly observed in cases of early preterms. In our department, a 29-year-old second gravida with metastatic breast cancer first diagnosed 7 years ago continued to receive trastuzumab treatment at her express request after detailed information and advice. Trastuzumab treatment had been started 1.5 years before the pregnancy after surgical removal of a lymph node metastasis. After 7 intravenous administrations at intervals of 3 weeks, an oligohydramnios occurred in the 24(th) week of pregnancy. For this reason, trastuzumab treatment was interrupted for 7 weeks, during which time the quantity of amniotic fluid returned to a normal level. As the 8(th) administration of trastuzumab led to a renewed oligohydramnios, the trastuzumab treatment was suspended until birth. The quantity of amniotic fluid having recovered to normal, labour was induced after 36 weeks of pregnancy, followed by a Caesarian section because of prolonged labour. The newborn boy showed no sign of respiratory or renal dysfunction and has developed normally, having at present reached the age of 3 years. From the few reported cases of pregnancies with trastuzumab therapy, it seems that an occurring oligohydramnios is the typical complication with the problem of life-threatening RDS after birth. Probably the reduction of amniotic fluid can be reversed by interrupting the trastuzumab therapy, as we observed in our case.

Introduction As the accurate diagnosis and treatment of gestational diabetes mellitus (GDM) is of increasing importance; new diagnostic approaches for the assessment of GDM in early pregnancy were recently suggested. We evaluate the diagnostic power of an ‘early’ oral glucose tolerance test (OGTT) 75 g and glycosylated fibronectin (glyFn) for GDM screening in a normal cohort. Methods and analysis In a prospective cohort study, 748 singleton pregnancies are recruited in 6 centres in Switzerland, Austria and Germany. Women are screened for pre-existing diabetes mellitus and GDM by an ‘early’ OGTT 75 g and/or the new biomarker, glyFn, at 12–15 weeks of gestation. Different screening strategies are compared to evaluate the impact on detection of GDM by an OGTT 75 g at 24–28 weeks of gestation as recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). A new screening algorithm is created by using multivariable risk estimation based on ‘early’ OGTT 75 g and/or glyFn results, incorporating maternal risk factors. Recruitment began in May 2014. Ethics and dissemination This study received ethical approval from the ethics committees in Basel, Zurich, Vienna, Salzburg and Freiburg. It was registered under http://www.ClinicalTrials.gov (NCT02035059) on 12 January 2014. Data will be presented at international conferences and published in peer-reviewed journals. Trial registration number NCT02035059.

Introduction Preeclampsia is a potentially life threatening disease occurring in pregnancy. The only causative cure consists in delivery with all the risks for a premature fetus. In preeclampsia, the lipid metabolism is substantially altered and lipid apheresis is being explored as a possible therapeutic approach to prolong preeclamptic pregnancies and allow further maturation of the fetus. In the Freiburg H.E.L.P.-Apheresis Study, 6 early onset preeclamptic patients were treated with H.E.L.P. apheresis. Objective/hypothesis Detailed analysis of apheresis-induced dynamics in serum lipid parameters. Methods 6 early onset preeclamptic patients underwent repeated apheresis treatments (n = 23). We evaluated parameters of the lipoprotein metabolism in 6 preeclamptic patients in detail. Results Reduction of lipoproteins by apheresis was lower than theoretically expected. Lipids reached previous pre-apheresis levels before the next apheresis even though apheresis was repeated within 2.9 ± 1.2 days. Fractional catabolic rates and synthetic rates were found to be substantially elevated, with fractional catabolic rates for ApoB/ LDL-cholesterol being 0.7 ± 0.3/ 0.4 ± 0.2 [day−1] and synthetic rates being 26 ± 8/ 17 ± 8 [mg*kg−1*day−1]. The distribution of LDL-subclasses after apheresis shifted to larger buoyant LDL, while IDL levels remained unaffected. Discussion Apheresis induced changes in lipoprotein profiles point to an underlying remnant removal disease like imbalance in plasma lipid conversion during preeclamptic conditions.

Background and Purpose— This study investigated whether a short testing of neurovascular coupling during midterm pregnancy could identify women at risk for subsequent preeclampsia. Methods— Transcranial Doppler sonography of the posterior cerebral artery during a brief visual stimulation was analyzed in 68 women at midterm pregnancy, the primary clinical end point was preeclampsia. Results— Women with bilateral notching of the uterine arteries showed an exaggerated visually evoked blood flow increase and longer time-to-peak. Neurovascular coupling was not significantly associated with the occurrence of preeclampsia. Conclusions— Neurovascular coupling was altered in women with impaired uteroplacentar vasoregulation but not a significant predictor of preeclampsia.

Implementation of guidelines for group B streptococcal (GBS) prepartum screening (PS) rarely has been prospectively evaluated. To assess PS at 35-37 weeks of gestation and compare its predictive value to that of an intrapartum screening (IS) within 7 days of delivery, a surveillance cohort study was conducted at a tertiary care center in Freiburg, Germany, during 2011-2012. Study participants included 937 pregnant women who had intrapartum cultures taken for vaginal and rectal GBS colonization. Colonization status was compared to PS, and intrapartum antibiotic prophylaxis (IAP) rates calculated. The neonates were tested for GBS transmission via cultures from their throats and external ear canals. While 67.5% (633/937) of study participants had a PS, only 22.7% (144/633) underwent a fully guideline-compatible PS. However, maternal GBS colonization rates were similar when comparing PS (18.5% [117/633]) versus IS (17.0% [133/784]). The positive predictive value of a positive PS result for GBS positivity at delivery was 77.2 %. Women with a positive PS received IAP in 89.3% of cases (75/84). The capsular serotype distribution pattern of colonizing GBS strains has not changed in comparison to our 2003-2004 study--one with a similar study design.Improved strategies for adoption of prepartum GBS screening are needed.• The prediction of prepartum GBS screening for intrapartum colonization status has not been well studied. • Longitudinal studies of GBS screening are needed for screening program evaluations and vaccine development. What is New: • The rate of GBS screening has improved over 10 years, and intrapartum GBS colonization prediction was accurate. • Serotype distribution was stable and suggests the potential long-term efficacy of GBS vaccines.

Background Preeclampsia (PE) is a life-threatening complication of pregnancy. To date the only therapy of severe PE consists in timely delivery of the fetus. In PE a deranged lipoprotein metabolism considered to impair endothelial function is observed. Heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.)-apheresis is an established method for lipoprotein removal and has already been successfully applied in PE. Recently, angiogenetic and anti-angiogenetic factors like placenta growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFlt-1) are discussed as risk factors and removal of sFlt-1 by dextran sulfate column (DCS) apheresis is suggested as specific cure for PE. By contrast, H.E.L.P.-apheresis does not remove sFlt-1. The present clinical trial revaluates the clinical efficacy of H.E.L.P.-apheresis in PE with focus on sFlt-1 and PlGF. Methods Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30–41 years) with very preterm PE (24 + 4 to 27 + 0 gestational weeks (GW)) (NCT01967355) compared to a historic untreated PE-group matching treated patients by GW at admission ( Results Women with PE received apheresis 2–6 times. In treated patients the average time from admission to birth was 15.0 days compared to 6.3 days in controls (p = 0.027). In treated patients the prolongation of gestation by apheresis converted to a mean fetal weight gain of 101 grams (p = 0.029). Lung maturation could be induced in all treated cases and all children could be dismissed in healthy condition. Apheresis significantly reduced levels of total cholesterol (−33%), triglycerides (−43%), and LDL-cholesterol (−44%). However, sFlt-1 was not reduced but levels significantly increased initially by H.E.L.P.-apheresis and dropped to almost pre-apheresis levels before next apheresis, with sFlt-1/PLGF ratio remaining unaffected. Conclusions H.E.L.P.-apheresis proved again to be a safe therapeutic option to prolong pregnancies in PE and results in significant fetal weight gain. However, H.E.L.P.-apheresis does not reduce circulating sFlt-1 levels. Thus, reducing lipids and other pro-inflammatory factors may be more relevant than reducing circulating sFlt-1 to improve outcome in PE.

Einleitung: Die Implantation einer Schwangerschaft in die Sectionarbe ist ein seltenes und schwerwiegendes Ereignis. Mogliche Komplikationen sind Ruptur in die Bauchhohle, operative fruhe Fruhgeburt und Hysterektomie. Behandlungsstrategie besteht ublicherweise in der operativen oder medikamentosen Beendigung der Graviditat. Das Austragen einer solchen Schwangerschaft ist mit einem hohen Risiko einer Ruptur mit vitaler Gefahrdung der Mutter verbunden. Fall: Eine 39-jahrige IV Gravida II Para, Z.n. 2 x Sectio, stellte sich in der 9+1. SSW in unserer Klinik vor. In der Sonografie zeigte sich die Graviditat in der Sectio-Narbe implantiert, das Cavum uteri leer. Der Trophoblast erschien nach ventral ohne myomentrane Wandung nur mit Serosa und Gefasen uberzogen. Trotz Risikoaufklarung und dringender Empfehlung zur Beendigung der Schwangerschaft entschied sich die Patientin fur das Austragen. Die stationare Uberwachung erfolgte ab der 26. SSW. Das Wachstum der Schwangerschaft entwickelte sich exzentrisch nach ventral und links entsprechend einer Zervixschwangerschaft mit extrauteriner Wachstumsrichtung. Bei unauffalligem weiterem Verlauf wurde die primare Sektio am 12.12.2013 in der 32+3 SSW durchgefuhrt. Intraoperativ prasentierte sich ein stark vorgewolbtes, aufgeweitetes und von Gefasen uberzogenes unteres Uterinsegment, lediglich von Serosa bedeckt. Nach problemloser Kindsentwicklung wurde nach Verschluss der Uterotomie bei belassener Plazenta die Hysterektomie durchgefuhrt. Der postoperative Verlauf war komplikationslos, der tiefste Hb lag bei 6,6 g/dl. Histologisch lag eine Plazenta accreta/increta in 90% der Haftungsfache vor. Kind: Junge, 1970 g, 8/10/10, pH: 7,29 Schlussfolgerung: Im hier vorgestellten Ausnahmefall kam es bei der beharrlichen Patientin mit guter Compliance zu einem uberraschend und nicht selbstverstandlich unauffalligen Verlauf der Schwangerschaft und relativ komplikationsarmer Geburt.

Objectives Alterations in lipoprotein metabolism have been proposed as a possible pathophysiologic factor for preeclampsia. Elevation of very low density lipoproteins (VLDL) and predominance of atherogenic small dense low density lipoproteins (sdLDL) have been demonstrated in preeclampsia. Heparin-mediated-extracorporeal-LDL-precipitation (H.E.L.P.)-apheresis is an established method for lipoprotein removal and regeneration of endothelial function in severe hyperlipidemia. Wang et al. (2006) successfully used H.E.L.P.-apheresis in a pilot study to prolong preeclamptic pregnancies. We investigated alterations in the lipidprofile and the effects of H.E.L.P.-apheresis in the prolongation of hypertensive pregnancies. Methods Six patients with early pregnancy complicated by hypertension were treated with H.E.L.P.-apheresis. Blood was collected before and after apheresis and subjected to ultracentrifugation for determination of lipid parameters. Results A total of 23 apheresis treatments (2–6 per patient) were performed without severe complications. Within apoB-containing lipoproteins, VLDL (−58%) and sdLDL (L5: −65% and L6: −68%) were removed at highest proportion. Cholesterol was reduced by 32% and triglycerides by 44%. Soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta-growth-factor (PlGF) were not removed by H.E.L.P. Pregnancies continued for 4–14 days and lung maturation was successfully initiated before termination of pregnancy by caesarean section. Conclusions H.E.L.P.-apheresis appears to preferentially address atherogenic lipoproteins, relevant to preeclampsia. Disclosures C. Contini: None. B. Konig: None. F. Markfeld-Erol: None. M. Kunze: None. S. Zschiedrich: None. H. Prompeler: None. G. Putz: None. K. Winkler: Commercial Interest: BBraun Melsungen AG provided the H.E.L.P.-system; Research Support: BBraun Melsungen AG; Speaker: BBraun Melsungen AG.