[Show abstract][Hide abstract] ABSTRACT: Background. Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.
BioMed Research International 04/2014; · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hintergrund Die Abrechnung stationärer Fälle in Deutschland erfolgt über das „German-Diagnosis-Related-Groups“(G-DRG)-System, das jährlich entsprechend den Veränderungen der Kosten und der Leistungserbringung angepasst wird. Dabei werden durch das DRG-Institut (Institut für das Entgeltsystem im Krankenhaus, InEK) der Selbstverwaltungspartner Daten der Leistungserbringer ausgewertet. Das InEK ist damit beauftragt, jährlich die DRG-Kalkulation entsprechend den vorliegenden Daten vorzunehmen und das System weiterzuentwickeln. Die Mitarbeit der Leistungserbringer ist hierzu unerlässliche Voraussetzung. Ziel Im Rahmen eines DRG-Evaluationsprojekts des Jahres 2012 hat es sich die Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) zur Aufgabe gemacht, für eine größere Verteilungsgerechtigkeit im Fach Gynäkologie und Geburtshilfe zu sorgen. Material und Methode Im Auftrag der DGGG wurden von Februar 2012 bis Juli 2012 gynäkologische Abteilungen deutscher Kliniken mit der Frage zur Bereitschaft an der Teilnahme an diesem Projekt angeschrieben. Neben einer finanziellen Beteiligung ging es um die Frage der Lieferung von Kosten- und Leistungsdaten aus 2011. Die gelieferten Kosten- und Leistungsdaten sollten den Daten entsprechen, die die Krankenhäuser auch dem InEK zur Verfügung gestellt hatten. Im Rahmen der Auswertung der ermittelten Daten wurden Unterfinanzierungen im DRG-System aufgedeckt, aber auch überproportional vergütete DRG identifiziert und entsprechende Vorschläge an das InEK zur gerechteren Umverteilung erarbeitet. Zusätzlich waren Veränderungen von Codes des Operationen- und Prozedurenschlüssels (OPS) und International Statistical Classification of Diseases and Related Health Problems (ICD) erforderlich, um die Fallschwere und Zuordnung der Fälle zu bestimmten DRG besser abbilden zu können. Ergebnis Die erarbeiteten Vorschläge wurden an das Deutsche Institut für Medizinische Dokumentation und Information (DIMDI) übermittelt. Über die Umsetzung der Anpassungsvorschläge zum G-DRG-System hat das InEK im September 2013 entschieden. Dabei ist ein Großteil der Vorschläge komplett oder in modifizierter Form aufgenommen worden. Das Fachgebiet hat sowohl durch eine gerechtere Verteilung als auch im Sinne von Mehrerlösen deutlich profitiert. Weitere, sich teils aus der Umsetzung ergebenden Vorschläge bzw. aufgrund der Kürze der Zeit nicht bearbeiteten Anregungen werden im nächsten Jahr von der DGGG erneut eingereicht. Schlussfolgerung Der finanzielle Druck der gynäkologisch/geburtshilflichen Kliniken wird sich durch die Weiterentwicklung des DRG-Systems nicht reduzieren lassen.
Der Gynäkologe 04/2014; 47(4):280-284. DOI:10.1007/s00129-014-3338-8
[Show abstract][Hide abstract] ABSTRACT: Lipocalins are a large protein family with only little sequence homology but highly conserved structural similarity. Many lipocalins play crucial roles in the generation of epithelial cancer, influencing pathways which regulate cell motility, cell differentiation and neovascularisation. Thereby they can be used as biomarkers of cancer, in most cases for a rather good prognosis. Glycodelin is a lipocalin existing in three isoforms which differ only by glycosylation, but which have different functions. In breast cancer, glycodelin A is known to contribute to a more differentiated cell morphology and is a biomarker for a favourable prognosis, but also plays a role in angiogenesis. Glycodelin A is a useful prognostic marker as it can be detected in serum samples, but is also a target for therapeutical interventions.
Anticancer research 03/2014; 34(3):1079-85. · 1.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
An association between malnutrition and poor patient outcome has been established in various medical fields, but there is a general lack of data on the prevalence of malnutrition among gynecologic patients. Therefore an assessment of malnutrition is needed to detect malnourished patients in gynecology and initiate nutritional therapy if needed.
Study design: Between 2011 and 2012 at our gynecologic department of a German university hospital, 397 patients were evaluated regarding the risk of malnutrition and occurrence of complications during the time of hospitalization. The Nutritional Risk Screening (NRS) 2002 system was used to estimate the risk level for malnutrition. Of the 397 patients, 336 received surgery and 61 were treated conservatively. Patients were included independently of surgical intervention or age. The parameters for the clinical outcome were complications and time of hospitalization.
A severe risk of malnutrition was diagnosed in 142 patients (35.8%) according to an NRS score of ≥ 3. Furthermore, a significantly higher complication rate among those patients who were at risk for malnutrition (NRS 1-2) (7.8%) or who were malnourished (NRS ≥ 3) (22.8%) was found (p < 0.001 χ2). Regarding the length of stay (LOS) in hospital, the medial hospitalisation time increased from 7 to 10 days when patients were malnourished (NRS score≥ 3) (p <0.001).
Malnutrition occurs frequently among gynecologic patients. Adequate perioperative nutritional supportive therapy should be considered in malnourished patients to improve their clinical outcome.
European journal of obstetrics, gynecology, and reproductive biology 03/2014; DOI:10.1016/j.ejogrb.2013.12.028 · 1.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background/Aim: Estrogen receptor-alpha is usually expressed in normal cervical tissue, but its presence is decreased or absent in invasive cervical cancer indicating that its expression is lost during development of invasive cervical cancer. The aim of the present study was to investigate ESR1 promoter methylation in cervical cancer and correlate methylation status with clinico-pathological parameters.
Fifty patients treated for cervical cancer were included in the study. Isolation and bisulfite treatment of genomic DNA from cervical cancer tissue was performed by commercially-available kits. Methylated ESR1 promoter sequences were detected by quantitative real-time methylation-specific PCR.
Methylation status did not present differences regarding age at-diagnosis, FIGO stage, grade, BMI and overall survival for all patients, but within the subgroup of non-keratinizing squamous cell cancer methylation status correlated with grading (p=0.047).
Methylation of the ESR1 promoter does not seem to be of any prognostic relevance, but is associated with higher tumor grading of cervical cancer patients.
Anticancer research 02/2014; 34(2):723-7. · 1.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Disseminated tumour cells (DTCs) in the bone marrow derive from many primary tumours, such as breast cancer. Their mere existence hints to present or future metastasis and implicates a worse prognosis for the patient. DTCs may possess different characteristics in comparison to the primary tumour due to events like Epithelial-Mesenchymal-Transition. Therefore, these cells might be able to survive chemotherapy and cause relapses of the disease at a later point. We aimed to detect and further characterise DTCs by an immunostaining approach with three different antigen markers (Her-2, MUC-1 and TF, also known as CD 176). For that reason, bone marrow of 41 breast cancer patients was obtained during surgery; DTCs were enriched by density gradient centrifugation and cytospins were prepared. After fixation, immunofluorescent double-stainings were carried out with antibodies against CD176 in combination with HER-2 or MUC-1. Cells co-expressing two antigens were found in all staining combinations (Her-2 and CD176: 46.14%; MUC-1 and CD176: 18.15% of all cases). Cells that stained for a single antigen only were also found (Her-2: 36.86%; MUC-1: 34.45%; CD176: 29.65% of all cases). Significant correlations between the stainings of all markers could be shown (p⟨0,001). In conclusion, Thomsen-Friedenreich Antigen (TF, CD176) is a promising marker in combination with the established marker Her-2 and other markers like MUC-1. These results may serve as a basis for future DTC detection routines and help to individualize medical treatment, reducing side effects and increasing the efficiency of the therapy.
Histology and histopathology 01/2014; · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Breast reconstruction with salpingo-oophorectomy can easily be performed in patients with genetic mutations increasing the risk for mammary and ovarian carcinoma. However, many patients are skeptical about having several surgeries, as they may result in additional anesthesiological risks as well as multiple visible scars. Therefore, the purpose of this study was to evaluate the feasibility of prophylactic mastectomy and breast reconstruction combined with simultaneous transmammary salpingo-oophorectomy for BRCA carriers.
Of the six patients (1 %) who chose prophylactic mastectomy with salpingo-oophorectomy at our hospital four patients had BRCA-1 mutations, one patient had a BRCA-2 mutation and one patient had a family inheritance pattern with no mutations. All patients chose to reduce their risk for mammary and ovarian cancer by undergoing bilateral mastectomy and bilateral salpingo-oophorectomy. Prophylactic mastectomy with immediate reconstruction was performed, followed by bilateral salpingo-oophorectomy with a procedure that relies on transmammary access and reduces the number of necessary surgeries without compromising cosmetic results, surgical risks and operating time.
The mean age of the patients was 46.7 ± 1.8 years (SD). The mean operative time was 190.2 ± 13.7 min. No complications were observed during the operations. The mean intra-operative loss of blood was 363.3 ± 77.9 ml. The operative method was successful in all six cases and was performed with no complications. All of the patients were satisfied with the cosmetic results.
In conclusion, prophylactic mastectomy and breast reconstruction combined with simultaneous laparoscopic salpingo-oophorectomy via transmammary access is feasible, easy to perform and provides an intriguing and novel approach to female BRCA carriers who desire operative prophylactic measures in one surgical session with no visible abdominal scars and no additional risks and complications.
Archives of Gynecology 01/2014; 289(6). DOI:10.1007/s00404-013-3133-0 · 1.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Knowledge on immunosuppressive factors in the pathogenesis of endometrial cancer is scarce. The aim of this study was to assess Glycodelin (Gd) and its immunosuppressive isoform Glycodelin A (GdA) in endometrial cancer tissue and to analyze its impact on clinical and pathological features and patient outcome.
292 patients diagnosed and treated for endometrial cancer were included. Patient characteristics, histology and follow-up data were available. Gd and GdA was determined by immunohistochemistry and in situ hybridization was performed for Gd mRNA.
Endometrial cancer shows intermediate (52.2%) or high (20.6%) expression for Gd in 72.8%, and GdA in 71.6% (intermediate 62.6%, high 9.0%) of all cases. The glycolysation-dependent staining of GdA is tumour specific and correlates with the peptide-specific Gd staining though neither of the two is associated with estrogen receptor, progesterone receptor or clinic-pathological features. Also Gd protein positively correlates with Gd mRNA as quantified by in situ hybridization. Gd positive cases have a favourable prognosis (p = 0.039), while GdA positive patients have a poor outcome (p = 0.003). Cox-regression analysis proofed GdA to be an independent prognostic marker for patient survival (p = 0.002), besides tumour stage, grade and the concomitant diagnosis of hypertension.
Gd and GdA are commonly expressed in endometrial cancer tissue and seem to be of relevance in tumourigenesis. They differ not only in glycolysation but also in their biological activity, since only GdA holds prognostic significance for a poor overall survival in endometrial cancer patients. This finding might be explained by GdAs immunosuppressive capacity.
BMC Cancer 12/2013; 13(1):616. DOI:10.1186/1471-2407-13-616 · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Breast cancer is still the most frequent cause of cancer-related death in women worldwide. Often death is not caused only by the primary tumour itself, but also by metastatic lesions. Today it is largely accepted, that these remote metastases arise out of cells, which detach from the primary tumour, enter circulation, settle down at secondary sites in the body and are called Circulating Tumour Cells (CTCs). The occurrence of such minimal residual diseases in the blood of breast cancer patients is mostly linked to a worse prognosis for therapy outcome and overall survival. Due to their very low frequency, the detection of CTCs is, still a technical challenge. RT-qPCR as a highly sensitive method could be an approach for CTC-detection from peripheral blood of breast cancer patients. This assumption is based on the fact that CTCs are of epithelial origin and therefore express a different gene panel than surrounding blood cells. For the technical approach it is necessary to identify appropriate marker genes and to correlate their gene expression levels to the number of tumour cells within a sample in an in vitro approach. After that, samples from adjuvant and metastatic patients can be analysed. This approach may lead to new concepts in diagnosis and treatment.
[Show abstract][Hide abstract] ABSTRACT: Cathepsin D is a protease involved in the metastasis and angiogenesis of mammary carcinomas. This review analyzes the significance of the tumor protease cathepsin D in mammary carcinomas as a tumor marker. We present a systematic overview based on a selective Medline search. Cathepsin D is expressed in mammary carcinomas and exhibits higher expression in invasive ductal carcinomas compared with lobular carcinomas. Nodal positive carcinomas showed reduced cathepsin D expression compared to lymph node metastases, and increased expression has been observed in hormone-receptor negative tumors. Thus, the expression of cathepsin varies between the two histological types. Increased cathepsin-D expression in acinar affection has also been described. The lack of an association of cathepsin D with known prognostic factors such as CA15-3, ERalpha and ERbeta does not prevent it from being using as a tumor marker. Cathepsin has already been used along with other genes as a prognostic parameter for carcinoma patients in gene arrays.
Histology and histopathology 11/2013; · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Aims: Peroxisome proliferator-activated receptor-gamma (PPARγ) plays an important role in insulin metabolism, trophoblast differentiation and anti-inflammatory circuits. The aim of this study was to investigate the expression of PPARγ in the placenta of patients with gestational diabetes mellitus (GDM) and the regulation of PPARγ by its agonists in trophoblast tumour cells BeWo in vitro. Methods: PPARγ expression in a total of 80 placentas (40 GDM/40 controls) was analysed by immunohistochemistry using the semi-quantitative immunoreactive score. Furthermore, a quantitative reverse transcription-polymerase chain reaction (PCR) was performed to determine the PPARγ mRNA-expression in both groups. We used a fused and a non-fused BeWo cell culture model for the stimulation with arachidonic acid and 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). Afterwards PPARγ mRNA-expression was analysed by quantitative real-time PCR (RT-PCR) (TaqMan). Results: Using immunohistochemistry we identified a decreased expression of PPARγ in the syncytiotrophoblast and the extravillous trophoblast of GDM placentas compared to normal controls. Furthermore, PPARγ mRNA-expression was reduced in GDM placentas. Stimulation of BeWo cells with arachidonic acid and 15d-PGJ2 caused a downregulation of PPARγ expression. Conclusion: As PPARγ is down regulated by arachidonic acid and 15d-PGJ2, the reduced PPARγ expression in GDM placentas may be due to an altered concentration of fatty acid derivates.
Journal of Perinatal Medicine 11/2013; 42(2):1-9. DOI:10.1515/jpm-2013-0039 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bei gesunden und erfahrenen Reiterinnen hat das Reiten während der Schwangerschaft keinen Einfluss auf die Schwangerschaftsdauer. Die Auswertung einer retrospektiven Befragung von 1851 Frauen, die vor oder während ihrer Schwangerschaft geritten sind, ergab keine Anhaltspunkte dafür, dass Reiten während der Schwangerschaft – auch nicht Springreiten oder berufsmäßiges, tägliches Reiten – zu einer erhöhten Rate an Aborten oder Fehl- bzw. Frühgeburten führt. Es fanden sich auch keine Hinweise auf vermehrte protrahierte Geburtsverläufe. Schwangere mit Frühgeburten hörten frühzeitiger mit dem Reiten auf als Schwangere mit Entbindung am Termin. Die Selbsteinschätzung der Schwangeren kann deshalb in der Beratung wichtige Hinweise geben. Jede elfte Reiterin hatte einen oder mehrere Unfälle beim Reiten oder beim Umgang mit dem Pferd. Das hohe Unfallrisiko muss mit der Schwangeren besprochen werden.
In healthy and experienced female riders horseback riding does not influence the duration of pregnancy. The analysis of a retrospective survey with 1,851 participants after childbirth or miscarriage who had partially continued riding during pregnancy showed no evidence for an increased rate of miscarriages or preterm delivery, not even in show jumping or professional daily riding. Prolonged labor could also not be found. Women with preterm delivery stopped riding activities earlier than women with term delivery. Self-assessment by pregnant women could therefore be an important indicator in medical care. Accidents while riding or having contact to horses occurred in 9.7 % of participants. When counselling pregnant riders, accidents resulting from horseback riding or other equestrian activities therefore represent a considerable risk and should be taken into account.
Der Gynäkologe 09/2013; 46(9):679-688. DOI:10.1007/s00129-013-3214-y
[Show abstract][Hide abstract] ABSTRACT: To evaluate sexual function among German urogynecological patients compared to a control group without urogynecological symptoms, using the validated German version of the Australian pelvic floor questionnaire.
Retrospective study including 313 women divided into five subgroups: women with stress urinary incontinence (SUI), overactive bladder (OAB), mixed incontinence (MI), pelvic organ prolapse (POP) and healthy controls. The self-administered questionnaire is divided into three domains: bladder, pelvic organ prolapse, and sexual function. It also includes severity, bothersomeness and condition-specific quality of life. Only completely filled out questionnaires were included. The Mann-Whitney U-test was used as a non-parametric test to calculate significances for ordinal data. A p-value <.05 was taken as significant.
16/59 (27.1%) women in the control group were not sexually active compared to 19/60 (31.7%) in the SUI group, 51/98 (52.0%) in the mixed-incontinence group, 19/43 (44.2%) in the OAB group, and 24/53 (45.3%) in the prolapse group. Coital incontinence was present significantly more often in women with SUI (15/41, 36.6%) or mixed incontinence (20/44, 45.5%) than among the controls (1/49, 2.1%). Hence, concerning sexuality, women with urogynecological symptoms were all significantly more affected than the healthy controls.
The German version of the Australian pelvic floor questionnaire is a feasible tool to evaluate not only symptoms of urinary incontinence and pelvic organ prolapse but also sexual dysfunction. A substantial proportion of our urogynecological patients suffer immensely from problems with their sexuality, and it is therefore our responsibility as physicians to provide assistance and improve our education in this field.
European journal of obstetrics, gynecology, and reproductive biology 08/2013; 170(2). DOI:10.1016/j.ejogrb.2013.08.002 · 1.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Follicle stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHCGR) were demonstrated to impact upon survival of patients suffering from epithelial ovarian cancer (EOC). Though structure wise the G-protein coupled estrogen receptor (GPER/GPR30) is related to FSHR/LHCGR, its prognostic impact in EOC remains controversial. We recently found that FSHR negative patients represent a specific EOC subgroup that may behave differently in respect to both treatment response and prognosis. Hence, the current study aimed to analyze how GPER may interact with the FSHR/LHCGR system in EOC and whether the prognostic significance of GPER in EOC cases (n = 151) may be dependent on the FSHR/LHCGR immunophenotype of the tumor. Ovarian cancer cell lines were used to study how FSH and LH regulate GPER and whether GPER activation differentially affects in vitro cell proliferation in presence/absence of activated FSHR/LHCGR. In EOC tissue, GPER correlated with FSHR/LHCGR and was related to prolonged overall survival only in FSHR/LHCGR negative patients. Although GPER was found to be specifically induced by LH/FSH, GPER agonists (4-Hydroxy-Tamoxifen, G1) reduced EOC cell proliferation only in case of LH/FSH unstimulated pathways. To the same direction, only patients characterized as LHCGR/FSHR negative seem to gain from GPER in terms of survival. Our combined tissue and in vitro results support thus the hypothesis that GPER activation could be of therapeutic benefit in LHCGR/FSHR negative EOC patients. Further studies are needed to evaluate the impact of GPER activation on a clinical scheme.
PLoS ONE 08/2013; 8(8):e71791. DOI:10.1371/journal.pone.0071791 · 3.23 Impact Factor