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Purpose: The identification of a robust IHC marker to predict the response to antiangiogenic bevacizumab in ovarian cancer is of high clinical interest. VEGF-A, the molecular target of bevacizumab, is expressed as multiple isoforms with pro- or antiangiogenic properties, of which VEGF-A165b is the most dominant antiangiogenic isoform. The balance of VEGF-A isoforms is closely related to the angiogenic capacity of a tumor and may define its vulnerability to antiangiogenic therapy. We investigated whether the expression of VEGF-A165b could be related to the effect of bevacizumab in advanced ovarian cancer patients. Experimental Design: Formalin-fixed paraffin-embedded tissues from 413 patients of the ICON7 multicenter phase III trial, treated with standard platinum-based chemotherapy with or without bevacizumab, were probed for VEGF-A165b expression by IHC. Results: In patients with low VEGF-A165b expression, the addition of bevacizumab to standard platinum-based chemotherapy significantly improved progression-free (HR: 0.727; 95% CI, 0.538–0.984; P = 0.039) and overall survival (HR: 0.662; 95% CI, 0.458–0.958; P = 0.029). Multivariate analysis showed that the addition of bevacizumab in low VEGF-A165b–expressing patients conferred significant improvements in progression-free survival (HR: 0.610; 95% CI, 0.446–0.834; P = 0.002) and overall survival (HR: 0.527; 95% CI, 0.359–0.775; P = 0.001), independently from established risk factors. Conclusions: We demonstrate for the first time that bevacizumab may differentially improve the prognosis of advanced ovarian cancer patients with low expression of VEGF-A165b, an antiangiogenic VEGF-A splice variant. We envision that this novel biomarker could be implemented into routine diagnostics and may have direct clinical implications for guiding bevacizumab-related treatment decisions in advanced ovarian cancer patients.

Purpose:The identification of a robust IHC marker to predict the response to antiangiogenic bevacizumab in ovarian cancer is of high clinical interest. VEGF-A, the molecular target of bevacizumab, is expressed as multiple isoforms with pro- or antiangiogenic properties, of which VEGF-A165b is the most dominant antiangiogenic isoform. The balance of VEGF-A isoforms is closely related to the angiogenic capacity of a tumor and may define its vulnerability to antiangiogenic therapy. We investigated whether the expression of VEGF-A165b could be related to the effect of bevacizumab in advanced ovarian cancer patients.Experimental Design:Formalin-fixed paraffin-embedded tissues from 413 patients of the ICON7 multicenter phase III trial, treated with standard platinum-based chemotherapy with or without bevacizumab, were probed for VEGF-A165b expression by IHC.Results:In patients with low VEGF-A165b expression, the addition of bevacizumab to standard platinum-based chemotherapy significantly improved progression-free (HR: 0.727; 95% CI, 0.538–0.984; P = 0.039) and overall survival (HR: 0.662; 95% CI, 0.458–0.958; P = 0.029). Multivariate analysis showed that the addition of bevacizumab in low VEGF-A165b–expressing patients conferred significant improvements in progression-free survival (HR: 0.610; 95% CI, 0.446–0.834; P = 0.002) and overall survival (HR: 0.527; 95% CI, 0.359–0.775; P = 0.001), independently from established risk factors.Conclusions:We demonstrate for the first time that bevacizumab may differentially improve the prognosis of advanced ovarian cancer patients with low expression of VEGF-A165b, an antiangiogenic VEGF-A splice variant. We envision that this novel biomarker could be implemented into routine diagnostics and may have direct clinical implications for guiding bevacizumab-related treatment decisions in advanced ovarian cancer patients.

Supplementary Figure from Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant

PURPOSE To compare standard versus extended duration of bevacizumab treatment in combination with front-line chemotherapy in women with newly diagnosed stage IIB-IV ovarian cancer. METHODS In this multicenter, open-label, randomized phase III trial (ClinicalTrials.gov identifier: NCT01462890 ), patients with newly diagnosed International Federation of Gynecology and Obstetrics stage IIB-IV epithelial ovarian, fallopian tube, or peritoneal cancer underwent primary cytoreductive surgery followed by six cycles of chemotherapy (paclitaxel 175 mg/m2 plus carboplatin area under the curve 5 once every 3 weeks) and bevacizumab (15 mg/kg once every 3 weeks). Patients were randomly assigned 1:1 to receive bevacizumab for either 15 or 30 months, stratified by International Federation of Gynecology and Obstetrics stage/residual tumor. The primary end point was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary end points included overall survival (OS), safety, and tolerability. RESULTS Between November 11, 2011, and August 6, 2013, 927 women were randomly assigned. There was no difference in PFS between treatment arms (hazard ratio, 0.99; 95% CI, 0.85 to 1.15; unstratified log-rank P = .90). Median PFS was 24.2 versus 26.0 months with standard versus extended duration of bevacizumab, respectively; restricted mean PFS was 39.5 versus 39.3 months, respectively. There was no OS difference between treatment arms (hazard ratio, 1.04; 95% CI, 0.87 to 1.23; P = .68). Serious/nonserious adverse events of special interest occurred in 29% versus 34% of patients in the standard versus experimental arms, respectively, and were consistent with the known safety profile of standard bevacizumab. CONCLUSION Longer treatment duration with bevacizumab for up to 30 months did not improve PFS or OS in patients with primary epithelial ovarian, fallopian tube, or peritoneal cancer. A bevacizumab treatment duration of 15 months remains the standard of care.

Fertility-sparing treatment in patients with cervical cancer should, in principle, follow identical algorithms to that in patients without future reproductive plans. In recent years, a trend towards non-radical procedures such as conization or simple trachelectomy has become apparent in medical literature, because of their associations with better pregnancy outcomes. However, the published reports included small numbers of patients and heterogenous treatment strategies to ascertain safety of such approaches.Our aims were to collect multi-institutional data regarding the oncological outcomes after fertility-sparing treatment in cervical cancer patients and to identify prognostic risk factors, including the influence of the radicality of individual cervical procedures.Patients aged 18-40 years with FIGO 2018 stage IA1 + lymphovascular space invasion or ≥IA2 cervical cancer who underwent any type of fertility-sparing procedure were eligible for this retrospective observational study, regardless of their histotype, tumor grade, and history of neoadjuvant chemotherapy. Associations between disease- and treatment-related characteristics with the risk of recurrence were analyzed.A total of 733 patients from 44 institutions across 13 countries were included in this study. Almost half of the patients had stage IB1 cervical cancer (49%), and two-thirds were nulliparous (66%). After a median follow-up of 72 months, 51 patients (7%) experienced recurrence of whom 19 (2.6%) died due to the disease. The most common sites of recurrence were the cervix (53%) and pelvic nodes (22%). The risk of recurrence was three times higher in patients with tumors2 cm in size than in patients with smaller tumors, irrespective of the treatment radicality (19.4% vs. 5.7%; hazard ratio 2.982, 95% CI 1.383-6.431, P = .005). The recurrence risk in patients with tumors ≤2 cm in size did not differ between patients who underwent radical trachelectomy or non-radical (conization and simple trachelectomy) cervical procedures (P = .957), regardless of tumor size subcategory (1 or 1-2 cm) or lymphovascular space invasion.Fertility-sparing non-radical cervical procedures were not associated with increased risk of recurrence compared with radical procedures in patients with tumors ≤2 cm in size in this large, multicenter retrospective study. The risk of recurrence after any type of fertility-sparing procedure was significantly greater in patients with tumors2 cm in size.

Background:\ud State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin–paclitaxel or carboplatin–gemcitabine) or the most active non-bevacizumab regimen: carboplatin–pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin–pegylated liposomal doxorubicin combined with bevacizumab.\ud Methods:\ud This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK. Eligible patients (aged ≥18 years) had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence more than 6 months after first-line platinum-based chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were stratified by platinum-free interval, residual tumour, previous antiangiogenic therapy, and study group language, and were centrally randomly assigned 1:1 using randomly permuted blocks of size two, four, or six to receive six intravenous cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (area under the concentration curve [AUC] 4, day 1) plus gemcitabine (1000 mg/m 2, days 1 and 8) every 3 weeks or six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (AUC 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m 2, day 1) every 4 weeks, both followed by maintenance bevacizumab (15 mg/kg every 3 weeks in both groups) until disease progression or unacceptable toxicity. There was no masking in this open-label trial. The primary endpoint was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy data were analysed in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov, NCT01837251.\ud Findings:\ud Between Aug 1, 2013, and July 31, 2015, 682 eligible patients were enrolled, of whom 345 were randomly assigned to receive carboplatin–pegylated liposomal doxorubicin–bevacizumab (experimental group) and 337 were randomly assigned to receive carboplatin–gemcitabine–bevacizumab (standard group). Median follow-up for progression-free survival at data cutoff (July 10, 2018) was 12·4 months (IQR 8·3–21·7) in the experimental group and 11·3 months (8·0–18·4) in the standard group. Median progression-free survival was 13·3 months (95% CI 11·7–14·2) in the experimental group versus 11·6 months (11·0–12·7) in the standard group (hazard ratio 0·81, 95% CI 0·68–0·96; p=0·012). The most common grade 3 or 4 adverse events were hypertension (88 [27%] of 332 patients in the experimental group vs 67 [20%] of 329 patients in the standard group) and neutropenia (40 [12%] vs 73 [22%]). Serious adverse events occurred in 33 (10%) of 332 patients in the experimental group and 28 (9%) of 329 in the standard group. Treatment-related deaths occurred in one patient in the experimental group (

We report recent progress in the development of a precision test for individualized use of the VEGF-A targeting drug bevacizumab for treating ovarian cancer. We discuss the discovery model stage (i.e., past feasibility modeling and before conversion to the production test). Main results: (a) Informatics modeling plays a critical role in supporting driving clinical and health economic requirements. (b) The novel computational models support the creation of a precision test with sufficient predictivity to reduce healthcare system costs up to $30 billion over 10 years, and make the use of bevacizumab affordable without loss of length or quality of life. (c) Connecting development of precision medicine tests to Randomized Clinical Trials enhances the robustness of computational modeling, accelerates development and validation of the precision test by 5-10 years, is highly generalizable and scalable, and should thus be considered as a high-priority design for similar precision medicine efforts.

Objectives: Increased glucose uptake and utilization is a major feature of malignant tumors. Recent studies suggest that the key mechanism of enhanced glucose metabolism in carcinoma cells involves the overexpression of transmembrane glucose transporter proteins (GLUTs). The aim of the present study was to analyze the expression of different GLUT isoforms (GLUT1–4) and to investigate whether alterations in their expression pattern accompany the malignant transformation and progression of ovarian cancer. Methods: Tumor tissue of 94 patients suffering from primary ovarian cancer (n = 78) or borderline tumors (n = 16) and tissue from 16 patients with benign ovarian changes were examined in this study. Immunohistochemistry was performed using polyclonal GLUT1–4 antibodies. GLUT1 protein expression was quantified by Western blot analysis. GLUT1 mRNA expression was analyzed by mRNA in situ hybridization. Results: All of the invasive carcinomas were positive for GLUT1. In contrast, GLUT1 expression was moderate in borderline tumors and weak to negative in all benign ovarian neoplasms. High GLUT1 mRNA levels were observed only in ovarian cancer. The intensity of GLUT1 expression in malignant ovarian neoplasms was associated neither with tumor characteristics nor with patient survival. Only GLUT3 revealed weak but homogeneous expression in human ovarian cancer as well as in benign ovarian tumors. GLUT2 and GLUT4 showed no expression in ovarian tissue. Conclusions: GLUT1 mRNA and protein were found to be expressed specifically in primary ovarian cancer. The close relationship between GLUT1 mRNA and protein expression points towards the potential relevance of GLUT1 as a diagnostic tool and therapeutic target in ovarian cancer.

The development of distant metastasis in breast cancer patients is the key step towards worse prognosis. The angiogenic basic fibroblast growth factor (bFGF) has been associated with tumorigenesis and metastasis in several human cancers. Therefore, bFGF expression was studied by immunohistochemistry in 111 patients with primary breast cancer. The results were correlated with prognostically relevant clinico-pathological features. such as tumor stage, grading. nodal stage and survival. bFGF was expressed in approximately 70% of the breast cancer tissues; 30% of the tumors showed strongly positive staining. With the exception of histological grading (p0.05), no correlation was found between the extent of bFGF expression and prognostic parameters. Analysis of survival showed a significantly (p0.05) prolonged survival for patients with a concomitant absence of axillary lymph node metastasis and bFGF immunoreactivity. Our data suggest that increased bFGF expression is a novel parameter for worse prognosis in nodal-negative breast cancer patients.

Objective. Theaim of the study was to investigate the role of 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) in the diagnosis of recurrent ovarian cancer. Methods. One hundred six FDG PET scans performed in 54 patients in the follow-up after cytoreductive surgery and chemotherapy of ovarian cancer were reevaluated. Fifty-eight scans were performed in patients with suspected recurrence and 48 scans in patients who were clinically disease free. Thirty-seven PET scans were validated by histology and 66 studies by a median follow-up of 22 months in disease-free patients or 12 months in patients with recurrent disease. Three scans were validated by concordant positive findings of tumor marker CA125, computed tomography, and FDG PET. Results. FDG PET correctly identified recurrent disease in 73/88 cases. PET ruled out recurrent disease in 15/18 cases. The sensitivity and specificity for PET were 83 and 83%, respectively. In patients with suspected disease, sensitivity was 94% compared to 65% in patients judged clinically disease free. The sensitivity of PET was 96% if suspicion of recurrence was based on a rise of CA125 alone. PET preceded the conventional diagnosis by a median of 6 months in patients judged clinically free of disease. The median relapse-free interval after a negative PET scan was 20 months. Conclusion. FDG PET provides the chance to detect recurrent ovarian cancer at an earlier stage during follow-up. Patients with a negative PET scan have a longer relapse-free interval than patients with a positive PET scan.

Infiltrating ductal (DC) and lobular carcinoma (LC) of the breast represent the most frequently observed varieties of invasive breast cancer, characterized by differences in their histological and clinical properties. Although comparative genomic hybridization (CGH) of invasive breast carcinomas has revealed a complex and consistent pattern of DNA copy number changes, the data with regard to type specific aberrations are limited. A comprehensive study was therefore performed on 19 LCs and 29 DCs to ascertain type-specific differences of unbalanced DNA copy number changes by CGH. Statistical analysis revealed significantly higher frequencies for underrepresentation of chromosomes 16q (p

Objective: To evaluate the results of reduction mammoplasty with a central and/or inferior pedicle. Methods: We reviewed 89 breasts in 50 patients operated on over a 30-month period. Three patients underwent oncoplastic procedures and 11 had reduction mammoplasties to match the contralateral breast. Results: The cosmetic results were good. The average amount of tissue removed per breast was 527 g (range, 36-1574g). The complication rate was 5.6%. There was one partial necrosis of the areola, which resolved with conservative treatment. No patient developed total nipple-areola necrosis. There was one postoperative infection. In general the scars were not visible. One patient had a slight separation at the junction of the inverted T. Conclusions: The advantages of reduction mammoplasty with a central and/or inferior pedicle include the latitude to resect breast tissue wherever required, final placement of the nipple at the end of the operation, and the ability for lactation and nursing. Thus this technique seems useful for young women, as a breast-sparing procedure in patients with cancer, and to match the opposite breast after mastectomy and reconstruction. Although no single mammoplasty technique is appropriate for all types of breast hypertrophy, this procedure seems safe, reliable and widely applicable.

For patients with carcinoma of the breast the detection of distant metastases means that definitive recovery is no longer possible, since any further treatment can only be palliative in nature. Consequently, the holistic approach of palliative medicine centres on the patients' quality of life, which is determined not only by their physical condition but also by their level of psychosocial wellbeing. In view of the pain experienced by 75 % of patients with metastatic mammary carcinoma and the effect of pain on their general wellbeing, adequate pain therapy, which can almost always be given by the oral route, so that outpatient treatment is possible, is the first priority. In addition, therapeutic control of other symptoms associated with the tumor or with the treatment is of fundamental importance. Care of these patients makes particular personal demands on the doctors, care staff, etc., to enable them to provide psychological and human support for those incurable patients in the final stage of their life.

Human papillomavirus (HPV) infection is common in cervical intraepithelial neoplasia (CIN). This study investigates HPV detection and typing assay based on polymerase chain reaction amplification of L1 open reading frame with general primers GP5/GP6, followed by enzyme-linked immunosorbent assay detection with type-specific DNA probes. To determine the sensitivity of this assay, formalin-fixed CaSki cells were used as reference cell lines. Fifty copies of viral DNA diluted in DNA from 100,000 noninfected cells could be detected. This assay was also investigated for HPV detection and typing of 67 cervical specimens diagnosed with with CIN III or carcinoma in situ (CIS) and their adjacent squamous epithelium. The CIN III lesions were infected in approximately 80% of the samples, 81% in the neighboring CIN II, and 68% in CIN I. The HPV infection was even detectable in 54% of nondysplastic epithelium located near a CIN III lesion.

Objective : Conventional transvaginal ultrasound- and transvaginal colour Doppler flow were used to assess morphology and circulation of pelvic masses. Study design : One hundred and nine adnexal masses in 101 women were examined between January 1993 and September 1994. Morphology was classified after a score published by Sassone et al. in 1991. Doppler waveforms using the lowest resistance index (RI), the pulsatility index (PI) and peak flow velocity were used for analysis. Ninety five patients underwent laparotomy. Following histopathological evaluation best cut-off values, sensitivity and specificity were calculated. Score results were compared with Doppler results and a combination of both methods. Results : A combination of Doppler sonography and conventional transvaginal sonography led to a sensitivity of 74.0% and a specificity of 73.7%. Eight out of 15 malignant masses were classified as stage I. An analysis of the false positive diagnoses showed that important information can be gained when Doppler sonography is performed. In particular, on solid appearing adnexal masses, Doppler sonography leads to a high accuracy (84.6%). Conclusion : Colour Doppler sonography is not applicable in routine clinical practice, but can give important additional information in specific cases. For solid appearing masses and in early ovarian malignancy, Doppler sonography facilitates the preoperative discrimination between benign and malignant processes.

Background: In comparison with normal cells glucose uptake and utilisation are increased in carcinomas. Glut-1 is a membrane glucose transport protein whose expression is elevated in a number of human solid tumours. The aim of this study was to evaluate the biologic significance of Glut-1 expression in ovarian cancer by immunohistochemistry. Methods: Paraffin-embedded tumour tissue of 52 patients with primary ovarian cancer was examined, 16 patients with benign ovarian tumours served as controls. Immunohistochemistry was performed using a polyclonal antibody (Biogenesis, New Field, UK) and an ABC-immunoperoxidase-technique. Semiquantitative histologic evaluation followed the criteria of the modified Remmele score. Results: 44/48 (92%) of invasive carcinomas stained positive for Glut-1. In contrast, Glut-1 was not detected in the borderline tumours or benign ovarian neoplasms. The expression of Glut-1 in malignant ovarian neoplasms was not associated with the biologic behavior or the survival. Conclusion: Glut-1 expression is increased in primary ovarian cancer. The lack of expression in benign and borderline tumours suggests that expression of Glut-1 is associated with the malignant transformation of ovarian tissue.

A 24-year-old patient with dysgerminoma of the right ovary and hypoplastic left ovary was screened for chromosomal aberration. Triple-X syndrome was found in the oral epithelium and lymphocyte culture, while chromosomal in situ hybridization of the tumor itself showed a normal XX karyotype. Although trisomy X and dysgerminoma are coincidental findings in our case report, women with malignant germ cell tumors and abnormal genitalia should be checked for chromosomal aberrations to exclude anomalies carrying a Y chromosome.

Sertoli-Leydig cell tumors (SLCTs) represent a rare group of sex-cord stromal tumors of the ovary of unknown pathogenesis. We report a SLCT of intermediate differentiation with peritoneal recurrence and lymph node metastasis 12 months after removal, including cytogenetic analysis by comparative genomic hybridization and fluorescence in situ hybridization, which showed trisomy 8 as sole unbalanced karyotypic aberration. Our results provide evidence that a simple numeric chromosomal abnormality in SLCT may be associated with a malignant phenotype and suggest that the molecular pathogenesis of SLCT may be different from ovarian granulosa-stromal cell tumors.

We report on a patient with an eight-year history on maintenance hemodialysis treatment without residual renal function in whom pregnancy was successfully managed through to the 29th week. During this time, under carefully modified dialysis treatment, the nephrologic course, as well as materno-fetal flow relationships were unremarkable. Fetal development was appropriate for gestational age. However, pregnancy was complicated by polyhydramnios, which necessitated i.v. tocolysis. In the 28 + 6th week of gestation, cesarean section was performed because of an antibiotic-resistant fever of unclear origin which ceased within two days of delivery. Although the postnatal course of the adequately developed baby was complicated by the respiratory distress syndrome, normal development continued. We emphasize that the intensive interdisciplinary cooperation of nephrologists and obstetricians is imperative for the successful management of pregnancy under these conditions. In these pregnancies, the main fetal problems consist of premature labor because of polyhydramnios, preterm delivery, intrauterine growth retardation and stillbirth. The mother is threatened by the development of superimposed pre-eclampsia, left ventricular failure because of volume overload and progressive anemia. In order to maintain a well-balanced homeostasis, intensification of dialysis therapy by an increase in frequency and duration is the most important therapeutic approach. Accurate fetal monitoring including frequent examination of the feto-maternal circulation by Doppler sonography as well as attentive surveillance of the mother is required to recognize the above mentioned complications.

The expression of growth factors is considered as an important diagnostic and prognostic feature in tumor pathology. We investigated the value of the immunohistochemical EGF-receptor expression (EGF-R) in 30 squamous cell carcinomas of the uterine cervix, treated by radical hysterectomy and lymphadenectomy according to the Wertheim-Meigs-Okabayashi technique. Immunohistochemical reactions were performed on 4 microm sections from paraffin-embedded tissue, using an indirect peroxidase method. The staining results were evaluated semiquantitatively as negative (n=9; 30%) or as slightly, moderately or severely positive (n=21; 70%). The EGF-R-negative tumors were found in less advanced tumor stages. None had invaded into the parametrium (100%), eight were staged as T1 (89%), seven as N0 (78%), and seven showed no evidence for lymphangiosis carcinomatosa (78%). The respective values for the EGF-R-positive tumors ranged from 52% to 67%. However, only the difference in parametral invasion (EGF-R-negative: 0%, EGF-R-positive: 38%) was statistically significant (p=0.0306), probably due to the small number of cases. The EGF-R-expression was not correlated to histomorphological tumor grading. The results of this study indicate an inverse correlation between EGF-R expression and tumor spread. Assuming that this trend could be confirmed by a larger group of patients, immunostaining for EGF-R in a tumor biopsy could be useful to adapt surgical strategies and adjuvant therapy in the individual patient. Moreover, the EGF-R is an interesting target for immunotherapeutic approaches in squamous cell cervical carcinoma.

Durch die erzielten Erfolge der assistierten Reproduktion bedingt wird der Geburtshelfer haufiger mit der Leitung von Mehrlingsgeburten betraut. Diese stellen sowohl in personeller als auch organisatorischer Hinsicht eine besondere Herausforderung fur die Klinik dar. Infolge der mit durchschnittlich 50 % hohen Fruhgeborenenrate mus bei der dementsprechend haufig notwendigen neonatologischen Primarversorgung gewahrleistet sein, das fur jedes Mehrlingskind ein personell und apparativ vollstandig ausgerustetes Team zur Verfugung steht. Bei hohergradigen Mehrlingen ist die primare Sectio als Entbindungsmodus der Wahl anzusehen. Die optimale Geburtsleitung bei Zwillingen wird national wie international kontrovers diskutiert, wobei prospektiv randomisierte Studien fehlen. Wahrend Einigkeit daruber besteht, das bei in Beckenend- oder Querlage befindlichem 1. Zwilling die Entbindung per primarer Sectio vorgenommen werden sollte, sind die Auffassungen uber das optimale geburtshilfliche Vorgehen, insbesondere bei Fruhgeborenen vor 32–34 SSW und bei Lageanomalie des 2. Zwillings, unterschiedlich. Angesichts der durch veranderte Indikationsstellung, forensische und organisatorische Grunde zunehmend limitierten Erfahrung vor allem jungerer Kollegen mit vaginal-operativen Entbindungen bei Beckenend- oder Querlage ist zu betonen, das die vaginale Geburtsleitung die ausreichende Erfahrung und sichere technische Beherrschung der geburtshilflichen Manover seitens des Geburtshelfers unbedingt voraussetzt. Neben diesen personellen und organisatorischen Aspekten sind auch die personliche Vorstellungen der Eltern bei der individuellen Entscheidung zur Geburtsleitung zu berucksichtigen.