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Denschlag D.,Frauenklinik | Thiel F.C.,Frauenklinik | Ackermann S.,Frauenklinik | Harter P.,Klinik fur Gynakologie und Gynakologische Onkologie | And 12 more authors.
Geburtshilfe und Frauenheilkunde | Year: 2015

Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Due to their rarity and their heterogeneous histopathology uterine sarcomas remain challenging tumors to manage and need a multidisciplinary approach. To our knowledge so far there is no evidence-based guideline on the appropiate management of these heterogeneous tumors. Methods: This S2k-guideline is the work of an representative committee of experts from a variety of different professions who were commissioned by the DGGG to carry out a systematic literature review of uterine sarcoma. Members of the participating scientific societies developed a structured consensus in a formal procedure. Recommendations: 1. The incidence and histopathologic classification of uterine sarcoma. 2. The clinical manifestations, diagnosis and staging of uterine sarcoma. 3. The management of leiomyosarcoma. 4. The management of endometrial stromal sarcoma and undifferentiated uterine sarcoma. 5. The management of adenosarcoma as well as carcinosarcomas. 6. The management of morcellated uterine sarcoma.

Hauptmann S.,Institute For Pathologie | du Bois A.,Klinik fur Gynakologie und Gynakologische Onkologie | Meinhold-Herlein I.,RWTH Aachen | Pfisterer J.,Zentrum fur Gynakologische Onkologie | Avril S.,TU Munich
Pathologe | Year: 2014

Histological grading of ovarian cancer has prognostic relevance and implications for treatment decisions. No standardized grading system has been established so far. Several grading systems are currently being used, including the FIGO, WHO, and Silverberg grading systems which cannot be directly translated into each other. Furthermore, individual grading criteria are not uniformly applicable to different histological subtypes. For serous ovarian cancer a binary grading system is now in use as the distinction between low-grade versus high-grade carcinomas reflects the different pathogenesis of these entities. Uniform guidelines for grading ovarian cancer are necessary and should ideally reflect the prognosis. This article provides an overview of commonly used grading systems and their prognostic value. The article demonstrates that a type-specific grading of ovarian cancer should be performed and recommendations for grading the various histological subtypes are given. © 2014, Springer-Verlag Berlin Heidelberg.

Eichbaum M.,University of Heidelberg | Mayer C.,University of Heidelberg | Eickhoff R.,Alcedis GmbH | Bischofs E.,University of Heidelberg | And 10 more authors.
BMC Cancer | Year: 2011

Background: The prognosis of patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC) is poor. There is no standard treatment available. Emerging evidence suggests a major role for antiangiogenic treatment modalities in EOC, in particular in combination with the metronomic application of low dose chemotherapy. The novel, investigational oral antiangiogenic agent pazopanib targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit is currently being studied in different tumour types and is already used as first line therapy in recurrent renal cell carcinoma. A combined therapy consisting of pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, pretreated EOC.Methods/design: This study is designed as a multicenter phase I/II trial evaluating the optimal dose for pazopanib (phase I) as well as activity and tolerability of a combination regimen consisting of pazopanib and metronomic cyclophosphamide in the palliative treatment of patients with recurrent, platinum-resistant, pre-treated ovarian cancer (phase II). The patient population includes patients with histologically or cytologically confirmed diagnosis of EOC, cancer of the fallopian tube or peritoneal cancer which is platinumresistant or -refractory. Patients must have measurable disease according to RECIST criteria and must have failed available standard chemotherapy. Primary objectives are determination of the optimal doses for pazopanib (phase I) and the overall response rate according to RECIST criteria (phase II). Secondary objectives are time to progression, overall survival, safety and tolerability. The treatment duration is until disease progression or intolerability of study drug regimen (with a maximum of 13 cycles up to 52 weeks per subject).Discussion: The current phase I/II trial shall clarify the potential of the multitargeting antiangiogenic tyrosinkinaseinhibitor GW 786034 (pazopanib) in combination with oral cyclophosphamide as salvage treatment in patients with recurrent, pretreated ovarian cancer.Trial registration: ClinicalTrials.gov: NCT01238770. © 2011 Eichbaum et al; licensee BioMed Central Ltd.

Reinartz S.,Universitatsklinikum | Pfisterer J.,Frauenklinik | du Bois A.,Klinik fur Gynakologie und Gynakologische Onkologie | Jackisch C.,Klinikum Offenbach GmbH | And 2 more authors.
Human Immunology | Year: 2010

The results of several clinical trials have clearly demonstrated the potential of the anti-idiotype (anti-Id) vaccine abagovomab to induce cancer antigen 125 (CA-125)-specific immunity in ovarian cancer patients. Because of the central role of regulatory T cells (Tregs) in tumor immunology, we analyzed the frequency and suppressive activity of CD25+FoxP3+ Tregs in 16 patients treated with abagovomab. During vaccination, mean frequencies of peripheral Treg with a CD4+CD25+FoxP3+ CD127- phenotype were enhanced but returned to baseline levels in the follow-up phase. Despite increasing Treg counts, the suppressive activity of Tregs was diminished in a subset of patients treated with abagovomab. Reduced Treg activity was associated with increasing polyclonal and CA-125-specific T-cell proliferation in these patients. Interestingly, CA-125-specific T-cell activation could not be further improved by Treg depletion in vitro, as CA-125 induced a suppressive CD4+CD25+FoxP3+ CD127- T cell subset derived from the originally Treg-depleted T-cell fraction. These CA-125-induced Tregs (iTregs) efficiently blocked polyclonal and tumor-specific T-cell activation. Further elimination of iTregs resulted in detectable CA-125-specific T-cell responses in a subset of patients. Based on our results, the suppressive potential rather than the frequency of natural and CA-125-induced Tregs is an important issues to consider for refinement of current anti-Id vaccination. © 2010 American Society for Histocompatibility and Immunogenetics.

Pfisterer J.,Zentrum fur Gynakologische Onkologie Kiel | Hilpert F.,Universitatsklinikum Schleswig Holstein Campus Kiel | Mahner S.,Universitatsklinikum Hamburg Eppendorf | Harter P.,Klinik fur Gynakologie und Gynakologische Onkologie | Du Bois A.,Klinik fur Gynakologie und Gynakologische Onkologie
Gynakologe | Year: 2013

Standard primary systemic treatment of patients with advanced ovarian cancer comprises six courses of intravenously administered carboplatin and paclitaxel. In patients with FIGO stage IIIB-IV disease, additional treatment with bevacizumab is possible. Primary, neoadjuvant treatment without prior debulking surgery should be avoided. Intraperitoneal treatments, including HIPEC, should only be given within controlled clinical trials. © 2013 Springer-Verlag Berlin Heidelberg.

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