Lukas Hefler

Karl Landsteiner Institut, Wien, Vienna, Austria

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Publications (271)865.21 Total impact

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    ABSTRACT: Objective: Large loop excision of the transformation zone (LLETZ) is the standard surgical treatment for cervical dysplasia. The optimal way to achieve local hemostasis in women undergoing LLETZ is unknown. Materials and methods: In a prospective, randomized trial, we compared spray coagulation and forced coagulation in women undergoing LLETZ in a 1:1 ratio. The primary endpoint was time to complete local hemostasis (TCLH). Secondary endpoints were blood loss (Δ hemoglobin before and after LLETZ), pain (numerical visual analog scale, 5-step graphical visual analog scale measured 2-3 hours after LLETZ), and perioperative/postoperative complications (intraoperative need for sutures, postoperative bleeding, infection, and unscheduled readmission). Analysis was by intention to treat. Results: One hundred fifty-one women were enrolled and were eligible for analysis. Mean (SD) TCLH in 80 women with forced coagulation was 43.3 (38.5) and 28.9 (22.9) seconds in 71 women with spray coagulation (p < 0.001). The secondary endpoints blood loss (Δ hemoglobin, -0.8 [0.8] vs -0.7 [1.1]; p = 0.115), pain (numerical visual analog scale, 4.1 [0.9] vs 4.2 [0.9]; p = 0.283, graphical visual analog scale (1.9 [1.3] vs 1.8 [1.3]; p = 0.888), and perioperative/postoperative complications (6/71 [8%] vs 7/80 [9%]; p = 0.822) were comparable between the 2 arms. In a multivariate analysis, coagulation method (odds ratio = 0.18; 95% CI = 0.09-0.38; p < 0.001) and size of the cervix (odds ratio = 2.43; 95% CI = 1.16-5.15; p = 0.021) were independent predictors of TCLH. Conclusions: Spray coagulation is superior to forced coagulation in women undergoing LLETZ and should be used as the standard approach.
    No preview · Article · Jan 2016 · Journal of Lower Genital Tract Disease
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    ABSTRACT: We reviewed the status of the use of the prophylactic long-acting granulocyte colony-stimulating factors (G-CSFs) pegfilgrastim and lipegfilgrastim in gynecologic malignancies. Long-acting G-CSFs should not be used in weekly regimens. Filgrastim is not indicated in patients with febrile and/or severe neutropenia after administration of long-acting G-CSF in the same cycle. One study has shown a moderate effect on febrile neutropenia of ciprofloxacin when co-administered with pegfilgrastim. There is broad evidence from meta-analyses that pegfilgrastim effectively reduces severe neutropenia. In parallel, its adverse effects have been studied extensively. All-cause mortality was significantly reduced by pegfilgrastim. The glycopegylated long-acting G-CSF, lipegfilgrastim has demonstrated antineutropenic efficacy similar to that of pegfilgrastimin in one breast cancer study. In another pivitol non-small cell lung cancer study, impaired survival was observed in the lipegfilgrastim group during the first 30 days of study. The European Medicines Agency claimed more profound safety data to be provided for lipegfilgrastim by 2017.
    No preview · Article · Oct 2015 · Wiener Medizinische Wochenschrift
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    ABSTRACT: The MPO system plays an important role in the control of infections and the deletion of malignant cells. Nevertheless, alternations in the MPO system can lead to DNA damage and carcinogenesis. Polymorphisms in the MPO Gene have been associated with an increased expression of MPO and a higher risk for development of cancer. This study evaluates the association between -463G/A MPO gene polymorphism and the risk for CIN. The MPO gene polymorphism (-463G/A) was investigated in 616 women with cervical intraepithelial neoplasia and in 206 healthy women. Association between MPO gene polymorphism and risk of cervical intraepithelial neoplasia were analyzed by univariate and multivariable models. No significant difference in genotype distribution of the MPO gene polymorphism was observed in women with CIN and controls (p = 0.4; OR 1.2, 95 % CI 0.8-1.6). A subgroup analysis only including women with CIN did not show an association between -463G/A MPO gene polymorphism and risk for high-grade CIN (CIN 2/3) (p = 0.09; OR 1.5, 95 % CI 0.9-2.3). The investigated MPO gene polymorphism is not associated with risk for the development of cervical intraepithelial neoplasia.
    No preview · Article · Aug 2015 · Archives of Gynecology
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    Elizabeth H Corder · Lukas A Hefler

    Full-text · Dataset · Jul 2015
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    Elizabeth H Corder · Lukas A Hefler

    Full-text · Dataset · Jul 2015
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    ABSTRACT: The internet has become an easily accessible and widely used source of healthcare information. There are, however, no standardized or commonly accepted criteria for the quality of Obstetrics and Gynecology websites. In this study, we aimed to evaluate the quality of websites of Obstetrics and Gynecology departments in German-speaking countries and to compare websites nationally and internationally. We scored 672 websites from Germany (n = 566), Austria (n = 57), and Switzerland (n = 49) using the objective criteria: Google search rank (2 items), technical aspects (11 items), navigation (8 items), and content (6 items) for a 26 point score. Scores were compared nationally and internationally. Multivariable regression models assessed good quality scores (≥50% of maximum) as the dependent variables and country, academic affiliation, being member of a healthcare consortium, confessional affiliation, and content management system (CMS) use as independent variables. The mean score of websites was 13.8 ± 3.3. 4.2% were rated as good (≥75% of maximum), 61.8% as fair (≥50% of maximum). German (14.0 ± 3.2) and Swiss (13.8 ± 4.0) websites scored significantly higher compared to Austrian websites (11.6 ± 2.5) (P < 0.001 and P = 0.005, respectively). Within Germany, academic had higher scores than non-academic departments (14.9 ± 3.2 vs. 13.7 ± 3.1, P < 0.001). Single institutions had higher scores compared to healthcare consortium institutions (14.1 ± 3.2 vs. 13.2 ± 2.6, P = 0.003). Departments in Northern and Southern states had higher scores compared to Eastern states (14.4 ± 3.2 and 14.2 ± 3.2 vs. 13.0 ± 3.0, P < 0.001). In multivariate regression models, all subscores (all: P < 0.001) independently predicted a website's reaching a good quality score, with navigation subscore as strongest predictor. Affiliations were predictors for some good individual subscores, but not for others. High content subscore was associated with good Google search rank, technical aspects, and navigation subscores. The quality of websites of Obstetrics and Gynecology departments varies widely. We found marked differences depending on country, affiliation, and region.
    Full-text · Article · Apr 2015 · BMC Pregnancy and Childbirth
  • A Wagener · AG Zeimet · D Reimer · L Hefler · H Koch

    No preview · Article · Apr 2015 · Geburtshilfe und Frauenheilkunde

  • No preview · Article · Apr 2015 · Geburtshilfe und Frauenheilkunde

  • No preview · Article · Apr 2015 · Geburtshilfe und Frauenheilkunde

  • No preview · Article · Apr 2015 · Geburtshilfe und Frauenheilkunde

  • No preview · Article · Apr 2015 · Geburtshilfe und Frauenheilkunde
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    ABSTRACT: Plasma fibrinogen is a key acute phase protein and known to be elevated in ovarian cancer. We aimed to investigate the association between plasma fibrinogen and malignant and benign ovarian tumors. In a retrospective, single-center study, we evaluated preoperative plasma fibrinogen levels in 471 patients with benign and in 224 patients with malignant (borderline ovarian tumor [BOT]: n=36, epithelial ovarian cancer [EOC]: n=188) ovarian tumors. The association between preoperative plasma fibrinogen levels and clinico-pathological parameters was investigated. A multivariate logistic regression model was performed to identify an independent association. Mean (standard deviation) preoperative plasma fibrinogen levels in patients with benign ovarian tumors, BOT, and invasive ovarian cancers were 346.7 (99.7), 372.8 (114), and 472.6 (148.4) mg/dL, respectively (p<0.001). Within the EOC cohort, patients with advanced stage disease had higher plasma fibrinogen levels (485.5 [151.3] mg/dL) than patients with early stage disease (430.9 [130.3] mg/dL; p=0.03). In a multivariate model plasma fibrinogen was identified to be independently associated with the presence of BOT and EOC. In the subgroup of patients <50years, plasma fibrinogen levels remained independently associated with malignant ovarian tumors in CA 125 positive and negative patients. Plasma fibrinogen levels are independently associated with malignant ovarian tumors. Plasma fibrinogen levels showed an independent association with malignant ovarian tumors in in the subgroup of patients <50years, in whom differential diagnosis of ovarian tumors is particularly challenging. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jan 2015 · Gynecologic Oncology
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    ABSTRACT: The aim of the present study was to assess if semen quality declines during in vitro fertilization (IVF) and whether or not this phenomenon is triggered by chronic male stress. In order to test this hypothesis, we first investigated a retrospective cohort of 155 male IVF patients (testing cohort). Subsequently, we started a prospective cohort study in men undergoing their first IVF and assessed semen quality and subjective male chronic stress using a validated tool, i.e. the Fertility Problem Inventory (FPI) questionnaire. The association between stress and sperm quality decline measured 4-6 weeks before the start of IVF (T1) and at the day of oocyte retrieval (T2) was the primary outcome. Live birth rate, first trimester abortion and rate of poor responders were secondary outcomes. In the testing cohort, mean progressive motility, but not mean sperm density significantly declined. There were 78/154 (51%) men who showed a decline in semen density and 50/154 (32%) men who showed a decline in progressive motility. In the validation cohort, progressive motility declined, whereas, sperm density increased from T1 to T2. Of 78 men, 27 men had increased stress (FPI-score > 146). Sperm density and progressive motility were not significantly different in men with and without stress. However, in the presence of male stress, couples had a higher rate of poor responders, miscarriages and a lower rate of live births. Subjective stress is not associated with a decline in semen quality observed during IVF but may be associated with adverse pregnancy outcome.
    Full-text · Article · Mar 2014 · Asian Journal of Andrology
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    ABSTRACT: To compare the skills of performing a vaginal breech (VB) delivery after hands-on training versus demonstration. We randomized medical students to a 30-min demonstration (group 1) or a 30-min hands-on (group 2) training session using a standardized VB management algorithm on a pelvic training model. Subjects were tested with a 25 item Objective Structured Assessment of Technical Skills (OSATS) scoring system immediately after training and 72h thereafter. OSATS scores were the primary outcome. Performance time (PT), self assessment (SA), confidence (CON), and global rating scale (GRS) were the secondary outcomes. Statistics were performed using the Mann-Whitney U-test, chi-square test, and multiple linear regression analysis. 172 subjects were randomized. OSATS scores (primary outcome) were significantly higher in group 2 (n=88) compared to group 1 (n=84) (21.18±2.29 vs. 20.19±2.37, respectively; p=0.006). The secondary outcomes GRS (10.31±2.28 vs. 9.17±2.21; p=0.001), PT (214.60±57.97s vs. 246.98±59.34s; p<0.0001), and CON (3.14±0.89 vs. 2.85±0.90; p=0.04) were also significantly different between groups, favoring group 2. After 72h, primary and secondary outcomes were not significantly different between groups. In a multiple linear regression analysis, group assignment (odds ratio [OR] 1.60; 95% confidence interval [CI] 1.14-2.05; p<0.0001) and gender (OR 2.91; 95% CI 2.45-3.38; p<0.0001) independently influenced OSATS scores. Hands-on training leads to a significant improvement of VB management in a pelvic training model, but this effect was only seen in the short term.
    No preview · Article · Sep 2013 · European journal of obstetrics, gynecology, and reproductive biology
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    ABSTRACT: Hypoalbuminemia, a known marker for malnutrition and increased morbidity and mortality, has been associated with impaired prognosis in different cancer entities. The present study investigates the prognostic value of pre-treatment serum albumin levels for survival in patients with endometrial cancer. Within the present cohort study, we evaluated 337 consecutive patients with endometrial cancer and investigated the association of pre-treatment serum albumin levels and clinical-pathological parameters. We performed univariate log-rank tests and multivariable Cox regression models to assess the association between pre-treatment serum albumin levels and survival. Pre-treatment serum albumin levels were inversely proportionally associated with FIGO tumor stage, histological grade, and patients' age. In a multivariable analysis pre-treatment serum albumin levels (p=0.02 and p=0.001), FIGO tumor stage (p<0.001 and p<0.001), and histological grade (p=0.002 and p<0.001) were independently associated with disease-free and progression-free survival, respectively. Pre-treatment serum albumin is a novel and independent prognostic parameter for disease-free and progression-free survival in patients with endometrial cancer.
    No preview · Article · Aug 2013 · European journal of obstetrics, gynecology, and reproductive biology

  • No preview · Article · Jun 2013 · Geburtshilfe und Frauenheilkunde
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    ABSTRACT: Objective: Endometriotic spread to the lymphatic system has been described, but little is known about the molecular events and changes in gene expression associated with this process. We sought to determine the expression levels of a panel of 28 genes in samples of primary endometriosis lesions (EL), isolated endometriotic-like cells (IELC)-positive pelvic sentinel lymph nodes (PSLN), and IELC-negative PSLN, in order to identify candidate genes that may play a role in this process. Study design: Quantitative real-time PCR and immunohistochemistry (IHC) of primary EL and PSLN samples with and without IELC from patients with ovarian and/or peritoneal endometriosis. Results: Gene expression was analyzed in EL (n=13), IELC-positive PSLN (PSLN+, n=11), and IELC-negative PSLN (PSLN-, n=8). Gene expression differences between PSLN+ and PSLN- were analyzed and evaluated in relation to their expression levels in EL. Genes expressed at high levels in EL but not in PSLN- and known to be expressed in IELC (such as ESR1, PGR) served as controls and the expected gene dilution effect was clearly observed. Expression of a set of genes (CXCR4, CD68, MKI67, and CD44) was found to be higher in PSLN+ vs. PSLN-, while lowest in EL, indicating upregulation in IELC. In contrast, EPCAM and E-cadherin, which were strongly expressed in EL, were not found to be expressed in PSLN+, and thus likely absent from IELC. IHC confirmed the expression of CXCR4, CD44s, and CD44v6 in IELC, as well as the absence of E-cadherin from IELC. Conclusion: Our data indicate that spread of endometriosis to PSLN is accompanied by differential expression of several genes, including EPCAM, CDH1 (E-cadherin), CXCR4, and CD44, suggesting an involvement of CD44 splice variants as well as CXCR4 signalling in this process.
    No preview · Article · Apr 2013 · European journal of obstetrics, gynecology, and reproductive biology
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    ABSTRACT: : To compare the skills of performing a shoulder dystocia management algorithm after hands-on training compared with demonstration. : We randomized medical students to a 30-minute hands-on (group 1) and a 30-minute demonstration (group 2) training session teaching a standardized shoulder dystocia management scheme on a pelvic training model. Participants were tested with a 22-item Objective Structured Assessment of Technical Skills scoring system after training and 72 hours thereafter. Objective Structured Assessment of Technical Skills scores were the primary outcome. Performance time, self-assessment, confidence, and global rating scale were the secondary outcomes. Statistics were performed using Mann-Whitney U test, χ test, and multiple linear regression analysis. : Two hundred three participants were randomized. Objective Structured Assessment of Technical Skills scores were significantly higher in group 1 (n=103) compared with group 2 (n=100) (17.95±3.14 compared with 15.67±3.18, respectively; P<.001). The secondary outcomes global rating scale (GRS; 10.94±2.71 compared with 8.57±2.61, respectively; P<.001), self-assessment (3.15±0.94 compared with 2.72±1.01; P=.002), and confidence (3.72±0.98 compared with 3.34±0.90, respectively; P=.005), but not performance time (3:19±0:48 minutes compared with 3:31±1:05 minutes; P=.1), were also significantly different, favoring group 1. After 72 hours, Objective Structured Assessment of Technical Skills scores were still significantly higher in group 1 (n=67) compared with group 2 (n=60) (18.17±2.76 compared with 14.98±3.03, respectively; P<.001) as were GRS (10.80±2.62 compared with 8.15±2.59; P<.001) and self assessment (SA; 3.44±0.87 compared with 2.95±0.94; P=.003). In a multiple linear regression analysis, group assignment (group 1 compared with 2; P<.001) and sex (P=.002) independently influenced Objective Structured Assessment of Technical Skills scores. : Hands-on training helps to achieve a significant improvement of shoulder dystocia management on a pelvic training model. : www.ClinicalTrials.gov, NCT01618565. : I.
    No preview · Article · Oct 2012 · Obstetrics and Gynecology
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    ABSTRACT: Cervical intraepithelial neoplasia (CIN) is a common disease among women of reproductive age. High-grade CIN lesions (CIN 2–3) are precancerous and can progress to cervical cancer. The most important risk factor for the development of CIN and progression to cervical cancer is persistent high-risk human papillomavirus (HPV) infection. The preferred treatment in most countries is surgical excision using conization. There is high need for a medical treatment alternative to surgical therapy for CIN 2–3 largely because of the risk of preterm birth and other long-term sequelae of cervical conization in future pregnancies. No medical therapy has been established in clinical practice for patients with CIN 2–3. In 2008, a study reported on the efficacy of imiquimod, a topical immune response modulator, against HPV-related vulvar intraepithelial neoplasia. Earlier this year, a randomized controlled trial found that combined use of imiquimod and conization did not improve CIN 2–3 recurrence rates compared with use of conization alone. However, the study had a number of design flaws. A major problem was the application of imiquimod only 5 times before surgery, an uncommon and short treatment regimen. The aim of the present randomized, double-blind, placebo-controlled phase 2 trial was to estimate the therapeutic efficacy of vaginal, self-applied imiquimod in women with high-risk HPV-positive CIN 2–3. Study subjects were 59 patients with untreated, histologically proven, high-risk, HPV-positive, and newly diagnosed CIN 2–3. Eligible women were randomized to receive either treatment with self-applied vaginal suppositories containing imiquimod or placebo for 16 weeks. The primary study outcome was efficacy, defined as histologic regression to CIN 1 or less following treatment. Secondary outcomes included complete histologic remission, HPV clearance, and treatment tolerability. A sample size of 24 patients per group was calculated to detect a 35% absolute increase in CIN 2–3 regression (imiquimod vs. placebo), assuming a 2-sided 5% significance level and a power of 80%. All patients tested positive for high-risk HPV at baseline. After 16 weeks of treatment, histologic regression to CIN 1 or less was achieved in 73% in the imiquimod group compared with 39% in the placebo group (P = 0.009). There was a higher complete histologic remission in the imiquimod group (47%) than in the placebo group (14%) (P = 0.008). Human papillomavirus clearance rates after treatment were 60% in the imiquimod group and 14% in the placebo group (P < 0.001). Complete remission rates among patients with HPV-16 infection were 47% in the imiquimod group and 0% in the placebo group (P = 0.003). Three of the 59 patients (5%), all within the placebo group, were found to have microinvasive cervical cancer after treatment. Topical imiquimod had no high-grade adverse effects; treatment was well tolerated. These findings suggest that vaginal imiquimod therapy is an efficacious, feasible, and well-tolerated medical treatment for patients with CIN 2–3.
    No preview · Article · Oct 2012 · Obstetrical and Gynecological Survey
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    ABSTRACT: Alternatives to surgical therapy are needed for the treatment of high-grade cervical intraepithelial neoplasia (CIN 2-3). We aimed to estimate the efficacy of a treatment with imiquimod, a topical immune-response modulator, in patients with CIN 2-3. Fifty-nine patients with untreated CIN 2-3 were randomly allocated to a 16-week treatment with self-applied vaginal suppositories containing either imiquimod or placebo. The main outcome was efficacy, defined as histologic regression to CIN 1 or less after treatment. Secondary outcomes were complete histologic remission, human papillomavirus (HPV) clearance, and tolerability. Assuming a two-sided 5% significance level and a power of 80%, a sample size of 24 patients per group was calculated to detect a 35% absolute increase in CIN 2-3 regression. Histologic regression was observed in 73% of patients in the imiquimod group compared with 39% in the placebo group (P=.009). Complete histologic remission was higher in the imiquimod group (47%) compared with the placebo group (14%) (P=.008). At baseline, all patients tested positive for high-risk HPV. Human papillomavirus clearance rates were increased in the imiquimod group (60%) compared with the placebo group (14%) (P<.001). In patients with HPV-16 infection, complete remission rates were 47% in the imiquimod group compared with 0% in the placebo group (P=.003). Microinvasive cancer was observed in three of 59 (5% [1-14%]) patients, all within the placebo group. Topical imiquimod treatment was well tolerated, and no high-grade side effects were observed. Topical imiquimod is an efficacious and feasible treatment for patients with CIN 2-3.
    Full-text · Article · Jul 2012 · Obstetrics and Gynecology

Publication Stats

4k Citations
865.21 Total Impact Points

Institutions

  • 2011-2015
    • Karl Landsteiner Institut
      Wien, Vienna, Austria
  • 2014
    • Krankenhaus der Barmherzige Schwestern
      Linz, Upper Austria, Austria
  • 1998-2013
    • Medical University of Vienna
      • • Department of Obstetrics and Gynecology
      • • Section for Clinical Biometrics
      Wien, Vienna, Austria
  • 2006
    • Duke University
      Durham, North Carolina, United States
  • 2004-2005
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 2001-2004
    • Martin Luther University Halle-Wittenberg
      • Clinic for Diagnostic Radiology
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 1998-2003
    • University of Vienna
      • Department of Gynecology
      Wien, Vienna, Austria
  • 2000-2002
    • Baylor College of Medicine
      • Department of Obstetrics and Gynecology
      Houston, Texas, United States
  • 1999
    • Medical University of Graz
      Gratz, Styria, Austria