Karl Landsteiner Institute for General Gynecology and Experimental Gynecologic Oncology

Vienna, Austria

Karl Landsteiner Institute for General Gynecology and Experimental Gynecologic Oncology

Vienna, Austria
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Background and purpose: Patients with recurrent cervical cancer (RecCC) who received definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT) as primary treatment are currently treated in our institution with palliative intent by chemotherapy (CHT) combined with bevacizumab (BEV). We aim to evaluate the risk of gastrointestinal (GI)/genitourinary (GU) fistula formation in these patients. Materials and methods: Data of 35 consecutive patients with RecCC treated initially with radiochemotherapy and IGABT were collected. Known and presumed risk factors associated with fistula formation were evaluated. Fistula rate was compared between patients receiving CHT or CHT+BEV. Results: Of the 35 patients, 25 received CHT and 10 patients received CHT+BEV. Clinical characteristics were comparable. Fistulae were reported in 6 patients: two fistulae (8%) in the CHT group, four (40%) in the CHT+BEV group. GU fistula occurred in the CHT+BEV group only (3/4). Of these 6 patients with fistulae, 5 (83%) had undergone previous invasive procedures after the diagnosis of RecCC and 1 patient had undergone pelvic re-irradiation; 3/6 patients had developed a local recurrence. No other risk factors for fistula formation were identified. Conclusion: In patients with RecCC after definitive radiochemotherapy including IGABT, the addition of BEV to CHT may increase the risk for GU fistula formation, particularly after invasive pelvic procedures. Future clinical studies are required to identify predictors for fistula formation to subsequently improve patient selection for the addition of BEV in the RecCC setting. © 2017 The Author(s)


Seebacher V.,Medical University of Vienna | Aust S.,Medical University of Vienna | D'Andrea D.,Medical University of Vienna | Grimm C.,Medical University of Vienna | And 8 more authors.
PLoS ONE | Year: 2017

Objective To develop a tool for individualized risk estimation of presence of cancer in women with adnexal masses, and to assess the added value of plasma fibrinogen. Study design We performed a retrospective analysis of a prospectively maintained database of 906 patients with adnexal masses who underwent cystectomy or oophorectomy. Uni- and multivariate logistic regression analyses including pre-operative plasma fibrinogen levels and established predictors were performed. A nomogram was generated to predict the probability of ovarian cancer. Internal validation with split-sample analysis was performed. Decision curve analysis (DCA) was then used to evaluate the clinical net benefit of the prediction model. Results Ovarian cancer including borderline tumours was found in 241 (26.6%) patients. In multivariate analysis, elevated plasma fibrinogen, elevated CA-125, suspicion for malignancy on ultrasound, and postmenopausal status were associated with ovarian cancer and formed the basis for the nomogram. The overall predictive accuracy of the model, as measured by AUC, was 0.91 (95% CI 0.87–0.94). DCA revealed a net benefit for using this model for predicting ovarian cancer presence compared to a strategy of treat all or treat none. Conclusion We confirmed the value of plasma fibrinogen as a strong predictor for ovarian cancer in a large cohort of patients with adnexal masses. We developed a highly accurate multivariable model to help in the clinical decision-making regarding the presence of ovarian cancer. This model provided net benefit for a wide range of threshold probabilities. External validation is needed before a recommendation for its use in routine practice can be given. © 2017 Seebacher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Polterauer S.,Medical University of Vienna | Polterauer S.,Karl Landsteiner Institute for General Gynecology and Experimental Gynecologic Oncology | Schwameis R.,Medical University of Vienna | Grimm C.,Medical University of Vienna | And 4 more authors.
Gynecologic Oncology | Year: 2017

Objective: To estimate the prognostic significance of lymph node ratio and number of positive nodes in vulvar cancer patients. Methods: This international multicenter retrospective study included patients diagnosed with vulvar cancer treated with inguinal lymphadenectomy. Lymph node ratio (LNR) is the ratio of the number of positive lymph nodes (LN) to the number of removed LN. Patients were stratified into risk groups according to LNR. LNR was correlated with clinical-pathological parameters. Survival analyses were performed. Results: This analysis included 745 patients. In total, 292 (39.2%) patients had positive inguinal LN. The mean (SD) number of resected and positive LN was 14.1 (7.6) and 3.0 (2.9), respectively. High LNR was associated with larger tumor size and higher tumor grade. Patients with LNRs 0% (N0), >. 0. <. 20%, and >. 20% had 5-year overall survival (OS) rates of 90.9%, 70.7%, and 61.8%, respectively (P <. 0.001). LNR was associated with both local and distant recurrence-free survival (P <. 0.001). Patients with 0, 1, 2, 3 or >. 3 positive lymph nodes had 5-year OS rates of 90.9%, 70.8%, 67.8%, 70.8% and 63.4% respectively (P <. 0.001). In multivariate analysis, LNR (P = 0.01) and FIGO stage (P <. 0.001), were associated with OS, whereas the number of positive nodes (P = 0.8), age (P = 0.2), and tumor grade (P = 0.7), were not. In high-risk patients, adjuvant radiotherapy was associated with improved survival. Conclusions: LNR provides useful prognostic information in vulvar cancer patients with inguinal LN resection in vulvar cancer. LNR allows for more accurate prognostic stratification of patients than number of positive nodes. LNR seems useful to select appropriate candidates for adjuvant radiation. © 2017.


Mailath-Pokorny M.,Medical University of Vienna | Polterauer S.,Medical University of Vienna | Polterauer S.,Karl Landsteiner Institute for General Gynecology and Experimental Gynecologic Oncology | Worda K.,Medical University of Vienna | And 2 more authors.
PLoS ONE | Year: 2015

Objective: To determine the association between isolated mid-trimester short fetal femur length and adverse perinatal outcome. Methods: This is a retrospective cohort study of patients with singleton gestations routinely assessed by second trimester ultrasound examination during 2006-2013. A fetal isolated short femur was defined as a femur length (FL) below the 5th percentile in a fetus with an abdominal circumference greater than the 10th percentile. Cases of aneuploidy, skeletal dysplasia and major anomalies were excluded. Primary outcomes of interest included the risk of small for gestational age neonates, low birth weight and preterm birth (PTB). Secondary outcome parameters were a 5-min Apgar score less than 7 and a neonatal intensive care unit admission. A control group of 200 fetuses with FL ≥ 5th percentile was used to compare primary and secondary outcome parameters within both groups. Chi-square and Student's t-tests were used where appropriate. Results: Out of 608 eligible patients with a short FL, 117 met the inclusion criteria. Isolated short FL was associated with an increased risk for small for gestational age (19.7% versus 8.0%, p = 0.002) neonates, low birth weight (23.9% versus 8.5%, p<0.001), PTB (19.7% versus 6.0%, p<0.001) and neonatal intensive care unit admissions (13.7% versus 3.5%, p = 0.001). The incidence of a 5-min Apgar score less than 7 was similar in both groups. Conclusion: Isolated short FL is associated with a subsequent delivery of small for gestational age and Low birth weight neonates as well as an increased risk for PTB. This information should be considered when counseling patients after mid-trimester isolated short FL is diagnosed. © 2015 Mailath-Pokorny et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Grimm C.,Medical University of Vienna | Hofstetter G.,Sloan Kettering Cancer Center | Aust S.,Medical University of Vienna | Mutz-Dehbalaie I.,Innsbruck Medical University | And 7 more authors.
British Journal of Cancer | Year: 2013

Background: Gamma-glutamyltransferase (GGT)-a membrane-bound enzyme crucially involved in the cell's detoxification pathway and apoptotic balance-is involved in tumour development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosis in gynaecologic cancers. The present study investigated the prognostic role of GGT in ovarian cancer patients. Methods: In this multicenter study, pre-therapeutic GGT levels were ascertained in 634 consecutive patients with epithelial ovarian cancer (EOC, n=567) and borderline tumour of the ovary (BTO, n=67). Gamma-glutamyltransferase serum levels were associated with clinicopathological parameters and uni-and multivariate survival analyses were performed. Immunohistochemistry of GGT was performed in ovarian cancer tissue and correlated with GGT serum levels.Results:Pre-therapeutic GGT serum levels were higher in patients with EOC (28.56 (38.24) U l-1) than in patients with BTO (20.01 (12.78) U l-1, P=0.01). High GGT serum levels were associated with advanced FIGO stage (P<0.001) and with worse overall survival in univariate (P<0.001) and multivariable analysis (P=0.02, HR 1.2 (1.1-1.5)). We further investigated the association between systemic GGT serum levels and local GGT expression in EOC tumour tissue and observed an association between these two parameters (P=0.03). Conclusion: High pre-therapeutic GGT serum levels are associated with advanced tumour stage and serve as an independent prognostic marker for worse overall survival in patients with EOC. Gamma- glutamyltransferase expression in ovarian cancer tissue is reflected in GGT serum levels. © 2013 Cancer Research UK. All rights reserved.


Seebacher V.,Medical University of Vienna | Bergmeister B.,Medical University of Vienna | Grimm C.,Medical University of Vienna | Koelbl H.,Medical University of Vienna | And 4 more authors.
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2016

Objective Metformin has recently been discussed to possess anticancer activities and to positively affect the risk of developing cancer. We performed the present study to investigate the association of metformin and survival in patients with endometrial cancer. Study design Within the present study we retrospectively reviewed the records of 465 consecutive patients with endometrial cancer. Drug intake of metformin was correlated with clinico-pathological parameters and the patients’ survival. Chi-square test, Kruskal Wallis test, the product limit method of Kaplan and Meier, and multivariable Cox regression models were used to assess associations between metformin and clinico-pathological parameters and survival, as appropriate. Results Eighty-seven (18.7%) patients suffered from diabetes and of these 46 (52.8%) used metformin at the time of diagnosis. When analysing all patients, metformin did not affect the patients’ survival. However, within the subgroup of overweight patients metformin was associated with a prolongation of overall survival (p = 0.04). Within this subgroup, diabetic patients who did not use metformin had a 2.3 times higher risk for death (95%CI 1.1–4.7; p = 0.02) compared to non-diabetic patients and diabetic patients using metformin. Metformin was not associated with prolonged recurrence-free or cancer-specific survival, irrespective of the patients’ body mass index (p = 0.08 and p = 0.4, respectively). Conclusion The results of our study might suggest a beneficial effect of metformin on overall survival in overweight diabetic patients with endometrial cancer. However, the question, if metformin can reduce the risk to die from endometrial cancer or improves all cause mortality only still remains open and needs further investigation. © 2016 Elsevier Ireland Ltd


Mailath-Pokorny M.,Medical University of Vienna | Schwameis R.,Medical University of Vienna | Grimm C.,Medical University of Vienna | Reinthaller A.,Medical University of Vienna | And 3 more authors.
BMC Pregnancy and Childbirth | Year: 2016

Background: To study the natural history of cervical intraepithelial neoplasia (CIN) during pregnancy and to compare the rates of persistence, progression and regression of CIN by colposcopically guided biopsy (CGB) during pregnancy with outcome in non-pregnant-women. Methods: A retrospective analysis of all pregnant women diagnosed with CIN at our outpatient clinic between 2005 and 2010 was performed. A CGB for histo-pathological analysis was obtained in all participants and observational management was performed. The histo-pathologic findings of initial and postpartum visits were collected. Rates of persistence, progression and regression of CIN were assessed. Results were compared to a matched control group of non-pregnant women where observational management was performed for at least three months. In addition a review of the literature and pooled analysis of published data was performed. Results: A total of 51 pregnant women with CIN were included into analysis. CIN 1, 2, and 3 was diagnosed by CGB in 33.3, 13.7 and 52.9 % of all pregnant women, respectively. The postpartum histo-pathologic evaluation of the pregnant cohort revealed a significantly higher tendency to spontaneous regression (56.9 versus 31.4 %, p = 0.010) and a considerably, but not significantly higher complete remission rate (41.2 versus 27.5 %, p = 0.144) when compared to the non-pregnant cohort. In addition, we observed a significantly lower CIN persistence rate than in the non-pregnant cohort (39.2 versus 58.8 %, p = 0.048). The progression rate was notably low in the pregnant cohort (3.9 %) and no progression to invasive cancer was observed. Conclusions: CIN lesions show considerably high spontaneous regression rates postpartum. Once presence of invasive cancer is ruled out definitive treatment can be deferred to the postpartum period. © 2016 Mailath-Pokorny et al.


Polterauer S.,Medical University of Vienna | Grimm C.,Medical University of Vienna | Hofstetter G.,Innsbruck Medical University | Concin N.,Innsbruck Medical University | And 7 more authors.
British Journal of Cancer | Year: 2012

Background: Nomograms are predictive tools that are widely used for estimating cancer prognosis. The aim of this study was to develop a nomogram for the prediction of overall survival (OS) in patients diagnosed with cervical cancer. Methods :Cervical cancer databases of two large institutions were analysed. Overall survival was defined as the clinical endpoint and OS probabilities were estimated using the Kaplan-Meier method. Based on the results of survival analyses and previous studies, relevant covariates were identified, a nomogram was constructed and validated using bootstrap cross-validation. Discrimination of the nomogram was quantified with the concordance probability.Results:In total, 528 consecutive patients with invasive cervical cancer, who had all nomogram variables available, were identified. Mean 5-year OS rates for patients with International Federation of Gynecologists and Obstetricians (FIGO) stage IA, IB, II, III, and IV were 99.0%, 88.6%, 65.8%, 58.7%, and 41.5%, respectively. Seventy-six cancer-related deaths were observed during the follow-up period. FIGO stage, tumour size, age, histologic subtype, lymph node ratio, and parametrial involvement were selected as nomogram covariates. The prognostic performance of the model exceeded that of FIGO stage alone and the models estimated optimism-corrected concordance probability was 0.723, indicating accurate prediction of OS. We present the prediction model as nomogram and provide a web-based risk calculator (http://www.ccc.ac.at/gcu). Conclusion :Based on six easily available parameters, a novel statistical model to predict OS of patients diagnosed with cervical cancer was constructed and validated. The model was implemented in a nomogram and provides accurate prediction of individual patients prognosis useful for patient counselling and deciding on follow-up strategies. © 2012 Cancer Research UK All rights reserved.


Polterauer S.,Medical University of Vienna | Polterauer S.,Karl Landsteiner Institute for General Gynecology and Experimental Gynecologic Oncology | Husslein H.,Medical University of Vienna | Kranawetter M.,Medical University of Vienna | And 5 more authors.
Journal of Surgical Education | Year: 2016

Background Laparoscopic surgical procedures require a high level of cognitive and psychomotoric skills. Thus, effective training methods to acquire an adequate level of expertise are crucial. The aim of this study was to investigate the effect of preoperative warm up training on surgeon's performance during gynecologic laparoscopic surgery. Materials and Methods In this randomized controlled trial, surgeons performed a preoperative warm up training using a virtual reality simulator before laparoscopic unilateral salpingo-oophorectomy. Serving as their own controls, each subject performed 2 pairs of laparoscopic cases, each pair consisting of 1 case with and 1 without warm up before surgery. Surgeries were videotaped and psychomotoric skills were rated using objective structured assessment of technical skills (OSATS) and the generic error rating tool by a masked observer. Perioperative complications were assessed. Statistical analysis was performed using a mixed model, and mean OSATS scores were compared between both the groups. Results In total, data of 10 surgeons and 17 surgeries were available for analysis. No differences between educational level and surgical experiences were observed between the groups. Mean standard error psychomotoric and task-specific OSATS scores of 19.8 (1.7) and 3.7 (0.2) were observed in the warm up group compared with 18.6 (1.7) and 3.8 (0.2) in the no warm up group, respectively (p = 0.51 and p = 0.29). Using generic error rating tool, the total number of errors was 8.75 (2.15) in the warm up group compared with 10.8 (2.18) in the no warm-up group (p = 0.53). Perioperative complications and operating time did not differ between both the groups. Discussion The present study suggests that warm-up before laparoscopic salpingo-oophorectomy does not increase psychomotoric skills during surgery. Moreover, it does not influence operating time and complication rates. (Medical University of Vienna-IRB approval number, 1072/2011, ClinicalTrials.gov number, NCT01712607). © 2016 Association of Program Directors in Surgery.


Mailath-Pokorny M.,Medical University of Vienna | Polterauer S.,Medical University of Vienna | Polterauer S.,Karl Landsteiner Institute for General Gynecology and Experimental Gynecologic Oncology | Kohl M.,Medical University of Vienna | And 4 more authors.
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2015

Objectives To construct two prediction models for individualized assessment of preterm delivery risk within 48 h and before completed 32 weeks of gestation and to test the validity of modified and previously published models. Study design Data on 617 consecutive women with preterm labor transferred to a tertiary care center for threatened preterm delivery between 22 and 32 weeks of gestation were analysed. Variables predicting the risk of delivery within 48 h and before completed 32 weeks of gestation were assessed and applied to previously published prediction models. Multivariate analyses identified variables that were incorporated into two modified models that were subsequently validated. Results Two modified prediction models were developed and internally validated, incorporating four and six of the following variables to predict the risk of delivery within 48 h and before completed 32 weeks of gestation, respectively: presence of preterm premature rupture of membranes and/or vaginal bleeding, sonographic cervical length, week of gestation, fetal fibronectin, and serum C-reactive protein. The correspondence between the actual and the predicted preterm birth rates suggests excellent calibration of the models. Internal validation analyses for the modified 48 h and 32 week prediction models revealed considerably high concordance-indices of 0.8 (95%CI: [0.70-0.81]) and 0.85 (95%CI: [0.82-0.90]), respectively. Conclusions Two modified prediction models to assess the risk of preterm birth were constructed and validated. The models can be used for individualized prediction of preterm birth and allow more accurate risk assessment than based upon a single risk factor. An online-based risk-calculator was constructed and can be assessed through: http://cemsiis.meduniwien.ac.at/en/kb/science-research/software/clinical-software/prematurebirth/. © 2014 Elsevier Ireland Ltd. All rights reserved.

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