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Einleitung: Lymphozelen stellen eine haufige Komplikation nach pelviner Lymphadenektomie bei Frauen mit gynakologischen Malignomen dar. Obwohl Lymphozelen zumeist asymptomatisch sind, kann eine Superinfektion eine medizinische oder mechanische Intervention notwendig machen. Eine unizentrische randomisiert kontrollierte Studie zeigte bereits erste Hinweise, dass ein Kollagen-Fibrin Vlies (Tachosil®) effektiv in der Pravention von asymptomatischen Lymphozelen sein konnte. Diese Studie war jedoch zu klein, um den klinisch wesentlich relevanteren Endpunkt – symptomatische Lymphozelen – zu evaluieren. Material und Methodik: Im Rahmen einer multizentrischen, verblindeten, randomisiert kontrollierten Arzneimittelgesetzstudie (Medizinische Universitat Wien, Ruhr Universitat Bochum, Charles Universitat Prag und Kliniken-Essen-Mitte) wurden 154 Frauen inkludiert, bei denen im Rahmen eines gynakologischen Malignoms (Zervix-, Endometrium- oder Ovarialkarzinom) eine pelvine Lymphadenektomie (LA) durchgefuhrt wurde. Frauen wurden intraoperativ nach durchgefuhrter pelviner LA in die Gruppe „Tachosil-Applikation“ oder „keine Tachosil-Applikation“ zugeteilt. Primarer Endpunkt war das Auftreten einer Lymphozele CTCAE v4.03 Grad > 2 innerhalb von 4 Wochen nach der Operation. Sekundarer Endpunkt war das Auftreten einer sonographisch verifizierten Lymphozele 4 Wochen nach Operation. Ergebnisse: 12/154 (7,8%) Frauen erschienen nicht zur Nachsorgeuntersuchung 4 Wochen nach der Operation. Symptomatische Lymphozelen traten insgesamt bei 9/142 (6,3%) Frauen nach pelviner LA auf. Es zeigte sich kein Unterschied in der Pravalenz der symptomatische Lymphozelen zwischen den beiden Gruppen (T: 7,9%, K: 5,1%; p = 0,5, OR 1,6 [0,4 – 6,3]). Auch in der Pravalenz der asymptomatischen Lymphozelen zeigte sich kein Unterschied zwischen den beiden Gruppen (T: 57,1%, K: 42,9%; p = 0,1, OR 1,9 [0,9 – 4,1]). Weiters zeigte sich kein Unterschied bei den schweren unerwunschten Nebenwirkungen, den intra- und postoperativen Komplikationen zwischen den beiden Gruppen. Im Rahmen einer multivariaten binaren logistischen Regression konnten keine pradiktiven Faktoren fur das Auftreten von symptomatischen Lymphozelen identifiziert werden. Diskussion: Die Applikation von Tachosil® nach pelviner Lymphadenektomie zeigte keine Wirksamkeit in der Vermeidung sowohl symptomatischer als auch asymptomatischer Lymphozelen bei Frauen mit gynakologischen Malignomen. Es konnten daruber hinaus keine pradiktiven Faktoren fur das Auftreten von symptomatischen Lymphozelen identifiziert werden.

PURPOSE: The influence of young maternal age on delivery mode is discussed controversially. MATERIAL AND METHODS: In a case-control study, we identified 381 women 18 years of age. The rates of vaginal instrumental delivery and caesarean section were defined as primary outcomes. Pregnancy complications and delivery characteristics were defined as secondary outcomes. RESULTS: Cases significantly more often had a spontaneous vaginal delivery compared to controls (78 [298/381] vs. 61 % [231/381], respectively; p < 0.001). Cases had a lower rate of caesarean section (16 [62/381] vs. 31 % [120/381]; p < 0.001). No difference was observed when comparing the rates of vaginal instrumental delivery (5 [20/381] vs. 8 % [30/381]; p = 0.2). Cases had a shorter mean duration of pregnancy (38.4 [SD 3.5] weeks of gestation vs. 39.0 [SD 2.6] weeks of gestation, p = 0.01), less significant maternal morbidity (1 vs. 6 %, p < 0.001), and delivered more often < 37 weeks gestation (15 vs. 9 %, p = 0.03) and < 34 weeks gestation (9 vs. 4 %, p = 0.02). CONCLUSION: Our data suggest that women < 18 years have a lower rate of caesarean section compared to older women, possibly due to a higher rate of preterm delivery.

Background: Fertility preservation by ovarian cryopreservation and heterotopic ovarian transplant is hampered by ischemic damage of the transplanted graft and poor oocyte viability. Design: Two longitudinal experiments were done - phase A: to evaluate if the administration of gonadotrophins (hMG) or vascular endothelial growth factor (VEGF) increases follicular survival after heterotopic autologous ovarian transplantation, and phase B: to determine if the administration of hMG enhanced neovascularization by increase in microvessel density in the heterotopic xenologous ovarian transplant. Methods: A: In three sheep, ovaries were removed and immediately transplanted into the abdominal wall. In one sheep, VEGF was administered at the transplantation site during surgery, the second was treated with hMG after transplantation for 2 weeks, and the third sheep served as control. B: The ovaries from two other sheep were removed, prepared in tissue pieces, and immediately grafted into the subcutaneous space of several combined immunodeficient (SCID-)mice (n=20). Following the transplantation, 10 of these mice (group 1) were treated with hMG until they were sacrificed, the other 10 untreated mice (group 2) served as controls. In each group, two mice were sacrificed at intervals of 2,4,6,10, and 14 days after grafting to permit histologic examination of the grafted tissue. Results: A: Whereas VEGF had no effect on follicular survival after transplantation (12.0% vs. 7.4%.),the administration of hMG increased follicular survival (12.0% vs. 29.0%). B: The use of hMG resulted in significantly higher numbers of microvessels per mm 2 (mean) at all of the time points studied - at 2 days 22 vs. 13 (p < 0.001), 4 days 22 vs. 13 (p < 0.001), 6 days 17 vs. 13 (p = 0.006), 10 days 28 vs. 12 (p < 0.001), and 14 days 35 vs. 16 (p

Polymorphisms are a potentially useful tool for assessing the individual physiology and risk profile of pregnancy-associated disorders. Associations between selected polymorphisms and preeclampsia and thrombosis have been evaluated in over 60 studies. We performed a meta-analysis of 22,11, and 10 association studies and demonstrated that presence of the F-V-Leiden G1691A (OR 1.9; 95% CI 1.6-2.5), the FII G20210A (OR 1.8; 95% CI 1.1-2.9), and the ACT Met235Thr polymorphism (OR 1.6; 95% CI 1.4-1.8), respectively, is significantly associated with preeclampsia. Presence of the MTHFR C677T polymorphism, however, is not associated with preeclampsia in a meta-analysis of 24 association studies (OR 1.1; 95% CI 0.9-1.3). Besides preeclampsia, genotyping for the F-V-Leiden G1691A and the FII G20210A polymorphisms is useful for individual risk assessment regarding pregnancy-associated thrombosis. Heterozygous and homozygous carriers of the F-V-Leiden G1691A polymorphism will develop this condition in 6.4% and 8.9% to 16.7% of cases, respectively. 6.2 % of women with the F II G20210A polymorphism and 17.8% of women with simultaneous carriage of the F-V-Leiden G1691A and FII G20210A polymorphisms will develop pregnancy-associated thrombosis. The thrombophilic polymorphisms F-V-Leiden G1691A and FII G20210A are also risk factors of early recurrent, late recurrent, and late spontaneous miscarriage based on a published meta-analysis of 31 studies. Six case-control and cohort studies of 687 women with thrombophilic polymorphisms demonstrate live birth rates of 82% (181/221) using low molecular weight heparin or fractionated heparin compared to 20% (95/466) without therapy (p < 0.001, OR 17.7; 95%-KI 12.2-25.5). Based on the data in the literature and a meta-analysis of 67 association studies, we conclude that the F-V-Leiden G1691A, FII G20210A, and ACT Met235Thr polymorphisms are significant risk factors for preeclampsia, pregnancy-associated thrombosis, and early and late miscarriages.

We present the case of an 84-year-old man with concomitant breast and prostate cancer. The patient presented with the clinical clinical picture of a T4-breast cancer. During preoperative staging prostate cancer was diagnosed. The patient received neo-adjuvant endocrine therapy followed by breast surgery and systemic endocrine therapy for breast and prostate cancer, respectively. We discuss treatment options in male breast cancer and the implications of concomitant prostate cancer.

Objective: Insulin-like growth factor (IGF)-binding protein (IGFBP)-related proteins (IGFBP-rPs) are recently described cysteine-rich proteins that share significant amino terminal structural similarity with the conventional IGFBPs and are involved in a variety of biological functions, including growth regulation and endothelial cell attachment and spreading. In an effort to screen for angiogenic factors in human granulosa cells (GC), we have identified and characterised a splice variant of IGFBP-7/ IGFBP-rP-1 (IGFBP-7v). Methods: The presence of IGFBP-7 and IGFBP-7 v variant was detected by RT-PCR in human granulosa cells derived from women undergoing in vitro fertilisation therapy. The nucleotide sequence was determined after subcloning and sequencing according to standard techniques. Computer analyses were performed at the ExPASy Molecular Biology server using the ClustalW alignment and protein analysis programms (http://www.expasy.ch). Results and Conclusions: The splice variant of IGFBP-7 (IGFBP-7 v) is 165 nucleotides smaller than conventional IGFBP-7 transcripts. The deletion occurs within exon 1 but does not lead to a frameshift or an aberrant termination of the deduced protein sequence. However, the IGFBP-7 consensus motif is deleted. In contrast to non-tumorigenic granulosa cells, IGFBP-7 v is not expressed in tumor cell lines of ovarian and cervical origins. Computer based analysis of IGFBP-7 v demonstrates that the deduced amino acid sequence lacks the IGFBP typical domain [(G)CGCCXXC], which is supposed to be involved in IGF binding suggesting an IGF independent action of IGFBP-7 v.

Malignant melanoma derives from pigmented cells of neuroectodermal origin. Melanoma cells express estrogen receptors. An influence of steroid hormones on the proliferation rate of melanoma cells was demonstrated in some animal experiments. Thus it is of concern whether or not women with malignant melanoma are candidates for hormone replacement therapy (HRT). Until today, no prospective randomized trial on the association between HRT and malignant melanoma has been published. However, from the data available from in vitro-studies, in vivo-studies, and epidemiological reports, we can draw the following conclusions: there is no convincing evidence that the intake of sexual steroids increases the risk for the development of malignant melanoma and there is no evidence that HRT, taken after a diagnosis of malignant melanoma, negatively influences the outcome of the disease.

Human papillomavirus (HPV) infection is the most important singular factor in the etiology of cervical cancer. Among young women, infection with HPV is a common and transient occurrence with prevalence rates between 20% and 46% and a mean duration of 8 months. Indications for HPV typing in current clinical practice include (1) triage to colposcopy and colposcopically directed biopsy, (2) triage to conization, (3) detection of HPV persistence after conization and (4) use of HPV within primary screening programmes of cervical cancer. Available data demonstrate that HPV typing increases the sensitivity of detecting severe dysplastic lesions among women with a diagnosis of atypical cells of undetermined significance (ASCUS), but not among women with a diagnosis of low grade squamous intraepithelial lesion (LSIL). This increased sensitivity, however, seems to be equivalent to that provided by repeat cervical cytology. Infection with HPV high risk types is strongly associated with disease progression of cervical dysplasia. Cases of severe dysplasia should be treated exclusively by surgical intervention. HPV typing might aid in the selection of women with established mild or moderate dysplasia, who should also undergo surgery. Whether an HPV-based approach in this clinical setting is safe as well as cost-effective, remains unclear. There is concern, that triaging women with mild or moderate dysplasia based on their HPV status might significantly increase treatment related morbidity due to the high prevalence of HPV infections among these women Persistence of high-risk HPV infection after surgical therapy of cervical dysplasia is significantly associated with residual disease and the risk of recurrence of dysplasia. Whether routine HPV typing before and after surgical therapy of cervical dysplasia is a superior strategy compared to cytologic follow-up examinations, has not been proven. Persistent HPV infection is the most important etiologic factor of cervical cancer. Many authors have therefore proposed to incorporate HPV typing into cervical cancer screening programmes. Up to date, however, there are no clinical studies available demonstrating the safety and efficacy of HPV typing, either alone or in combination with cervical cytology, in population-based screening programmes. In summary, there is not enough evidence today to support the routine use of HPV typing in common clinical practice.

Etiologic factors associated with habitual pregnancy loss include uterine anomalies, luteal phase defects, hyperprolactinemia, hyperandrogenemia, genital infections, and balanced chromosomal translocations. The diagnostic work-up should be planned accordingly. Normally the maternal immune system recognizes paternally-derived fetal and placental antigens and confronts the embryo/fetus with a host defense response. To avoid rejection of the semiallogenic embryo/fetus, the maternal immune system is suppressed. Imbalances in the complex immunologic interactions between mother and embryo/fetus increase the risk for spontaneous abortion. Women with habitual abortion can show characteristic deficiencies in autoimmune components (e.g., the antiphospholipid syndrome) or alloimmune components (e.g., TH-1/TH-2 ratio and asymmetrically glycosylated blocking antibodies). Treatment options based on level-II evidence include progesterone, folate, aspirin, heparin, and cortisone.

Cervical cytology screening programmes have significantly reduced cervical cancer mortality. In 1988 the National Cancer Institute developed a new classification for reporting cervical cytology--"The Bethesda System". The aim of our study was to compare the clinical usefulness of this new classification with the classification used in German-speaking countries (which discriminates cytologically between moderate and severe dysplasia) including a verbal classification predicting the histological grade of cervical intraepithelial neoplasia (CIN I, II, III). 671 patients with abnormal cervical cytology results and subsequent conisation or hysterectomy were included. We correlated cytological and histological diagnosis (gold standard). In cases of cytologically suggested moderate dysplasia we found histologically CIN I, CIN II and CIN III in 11%, 41% and 42%, respectively. Our results show that discrimination of CIN II and CIN III by means of cytology is limited. Using our therapy schedules we found that adequate therapy is possible by each of the cytological classification systems. The cervical smear is used as a screening test to determine which women require further examination using colposcopy. Under these circumstances an adequate therapy is possible with both classifications. The results underline the importance of colposcopy in the management of cervical dysplasia. As long as conisation is commonly used in German-speaking countries as the only diagnostic tool after an abnormal cervical smear the Bethesda System increases the risk of overtreatment.

Fragestellung: Das C-reaktive Protein (CRP) ist ein bekannter Marker akuter und chronischer inflammatorischer Prozesse. Daruber hinaus zeigten rezente Daten, dass CRP einen potentiellen unabhangigen prognostischen Marker des Ovarialkarzinoms darstellt. Im Gegensatz zu dem einzigen etablierten Prognoseparameter CA-125, fehlt derzeit jedoch ein definierter pathologischer Grenzwert. Ziel dieser Studie war es einen prognostischen CRP-Grenzwert bzw. Risikogruppen zu definieren. Methodik: In dieser multizentrischen, retrospektiven Studie wurden die praoperativen CRP-Serumspiegel von 623 Patientinnen mit epithelialem Ovarialkarzinom (EOC) erhoben. CRP wurde mithilfe multivariater Cox-Regressionsmodelle als unabhangiger prognostischer Parameter evaluiert und mittels statistischer Modelle der optimale prognostische Grenzwert analysiert. Prognostische Risikogruppen wurden definiert. Ergebnisse: CRP zeigte eine unabhangige Assoziation mit dem rezidivfreien Uberleben (p 15mg/dL=Gruppe 3) definiert werden: Gruppe 2 zeigte im Vergleich mit Gruppe 1 eine Hazard Ratio (HR) 3,3 (95% Konfidenzintervall 1,6–7,0), Gruppe 3 verglichen mit Gruppe 2 eine HR 1,6 (1,0–2,6) fur das Gesamtuberleben. Schlussfolgerung: CRP zeigte eine unabhangige Assoziation mit der Prognose von Patientinnen mit EOC, wobei ein hoher praoperativer CRP-Serumspiegel mit einer schlechten Prognose einherging. Aufgrund der linearen Assoziation war die Stratifizierung in drei prognostische Risikogruppen moglich, nicht jedoch die Definition eines eindeutigen prognostischen CRP-Grenzwertes.

1. Fragestellung: Der Transkriptionsfaktor Oct-4 ist zur Erhaltung der Pluripotenz einer Korperzelle notwendig und wird von allen Stammzellen exprimiert. Oct-4 konnte bisher neben embryonalen Stammzellen auch in Malignomzellen und im menschlichen Endometrium nachgewiesen werden. Ziel dieser Arbeit war es die Expression von Oct-4 in Abhangigkeit von der Phase des Menstruationszyklus zu untersuchen. 2. Methodik: Es wurden Endometriumproben von 49 hormonnaiven Frauen mit regelmasigen Monatszyklen (25–35d) entnommen. Die Expression von Oct-4 im Endometrium wurde mittels Immunhistochemie (IHC) und RT-PCR untersucht. 3. Ergebnisse: In allen Gewebeproben konnte Oct-4 mittels RT-PCR nachgewiesen werden. Die mittlere Oct-4-Expression in der Follikelphase, Lutealphase und der Menstruation betrug 15 123,0 (±10 247,5) idv (integrated density value), 14 359,3 (±8811,9) idv und 16 768,9 (±705,1) idv. Es konnte kein signifikanter Unterschied im Vergleich der Zyklusphasen festgestellt werden (Follikelphase vs. Lutealphase; p=0,8; Follikelphase vs. Lutealphase vs. Menstruation; p=0,7). Die Daten zur Expression von Oct-4 auf Proteinebene (IHC) werden nachgereicht. 4. Schlussfolgerung: Unsere Daten zeigen, dass Oct-4 sowohl wahrend der Follikelphase als auch wahrend der Lutealphase und Menstruation im Endometrium exprimiert wird. Es besteht keine Korrelation zwischen der Oct-4 Expression im Endometrium und der Zyklusphase. Endometriumzellen aller Zykluspahsen sind potenzielle Quellen von adulten Stammzellen.