Publications by authors named "Markus C Fleisch"

The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020.

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Article Synopsis
  • - The S3-guideline for endometrial cancer, initially released in April 2018, underwent a comprehensive review and update from April 2020 to January 2022, as requested by German Cancer Aid and coordinated by prominent gynecological and oncology organizations in Germany.
  • - The update focused on integrating new evidence and refining recommendations to enhance treatment approaches, emphasizing personalized therapies to minimize unnecessary radical surgeries and non-beneficial adjuvant treatments for low-risk patients.
  • - The revised guideline aims to optimize care for high-risk patients by clarifying the roles of radical surgery and additional treatments, ultimately improving survival rates and quality of life, while serving as a foundation for certified gynecological cancer centers.
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Positioning injuries are relatively common, forensically highly relevant complications of gynecologic surgery. The aim of this official AWMF S2k-guideline is to provide statements and recommendations on how to prevent positioning injuries using the currently available literature. The literature was evaluated by an interdisciplinary group of experts from professional medical societies.

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Endometrial cancer (EC) is the most common cancer affecting the female reproductive organs in higher-income states. Apart from reproductive factors and excess weight, genetic predisposition is increasingly recognized as a major factor in endometrial cancer risk. Endometrial cancer is genetically heterogeneous: while a subgroup of patients belongs to cancer predisposition syndromes (most notably the Lynch Syndrome) with high to intermediate lifetime risks, there are also several common genomic polymorphisms contributing to the spectrum of germline predispositions.

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BRCA1 deficiency may perturb the differentiation hierarchy present in the normal mammary gland and is associated with the genesis of breast cancers that are genomically unstable and typically display a basal-like transcriptome. Oriented cell division is a mechanism known to regulate cell fates and to restrict tumor formation. We now show that the cell division axis is altered following shRNA-mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated normal human mammary cells with graded consequences in progeny cells that include aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective loss of cells with luminal features.

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Construction of a mitotic spindle requires biochemical pathways to assemble spindle microtubules and structural proteins to organize these microtubules into a bipolar array. Through a complex with dynein, the receptor for hyaluronan-mediated motility (RHAMM) cross-links mitotic microtubules to provide structural support, maintain spindle integrity, and correctly orient the mitotic spindle. Here, we locate RHAMM to sites of microtubule assembly at centrosomes and non-centrosome sites near kinetochores and demonstrate that RHAMM is required for the activation of Aurora kinase A.

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Purpose: This study was aimed to investigate incidence, circumstances and consequences of acute compartment syndrome (CS) of the lower extremity after gynecological operations in lithotomy position by collecting data from departments of Obstetrics and Gynecology in Germany.

Design: Retrospective observational study.

Setting: Departments of Obstetrics and Gynecology in the area of North Rhine (Germany)

Methods: A 24-item questionnaire was sent to 168 gynecological departments.

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Compartment syndrome (CS) of the lower leg is a rare but severe complication of operations in the lithotomy (LT) position after urologic, gynecologic and general surgery. A delay in diagnosis and treatment can lead to loss of function and even life-threatening complications. The pathophysiology is still not fully understood but it is believed that ischemia as a result of increased compartment pressure and decreased perfusion pressure may lead to CS.

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Ovarian cancer patients often suffer from malignant ascites and pleural effusion. Apart from worsening the outcome, this condition frequently impairs the quality of life in patients who are already distressed by ovarian cancer. This study investigated whether single intraperitoneal administration of the anti-VEGF antibody bevacizumab is capable of reducing the ascites-related body surface and prolonging survival.

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Purpose: Targeted oncolytic adenoviruses capable of replication selectively in cancer cells are an appealing approach for the treatment of various cancer types refractory to conventional therapies. The aim of this study was to evaluate the effect of Ad5/3MDR1E1, a multidrug resistance gene 1 (MDR1)-targeted fiber-modified replication-competent adenovirus for the therapy of platinum-pretreated ovarian cancer in combination with cytostatic agents.

Methods: MDR1-specific tumor cell killing of Ad5/3MDR1E1 was systematically evaluated in chemotherapy naïve and pretreated ovarian cancer cells in vitro.

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Article Synopsis
  • The study looks at how normal breast cells stay organized and the role of a gene called BRCA1 in preventing breast cancer.
  • When BRCA1 isn't working well, it can lead to more stem cells in the breast, which may increase the risk of developing tumors.
  • Researchers found that another gene, RHAMM, works with BRCA1 to keep cell organization, and changes in these genes could help understand both hereditary and common types of breast cancer.
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We report a 66-year-old woman with slowly progressive ataxia due to cerebellar atrophy. Imaging studies revealed multiple lesions in both the lungs and dorsal subpleural space. A biopsy identified the lesions as metastases of a low-grade endometrial stromal sarcoma containing sex-cord elements.

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We have built a novel computational microscopy platform that integrates image acquisition, storage, processing and analysis to study cell populations in situ. This platform allows high-content studies where multiple features are measured and linked at multiple scales. We used this approach to study the cellular composition and architecture of the mouse mammary gland by quantitatively tracking the distribution and type, position, proliferative state, and hormone receptor status of epithelial cells that incorporated bromodeoxyuridine while undergoing DNA synthesis during puberty and retained this label in the adult gland as a function of tissue structure.

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For 20 years laparoscopic pelvic and para-aortal lymph node dissection has become increasingly popular as part of minimally invasive surgical treatment concepts for women suffering from gynaecological malignancies. Especially patients suffering from early-stage cervical or endometrial cancers can benefit from the general advantages of a minimally invasive procedure if a comparable degree of radical surgery is achieved. The feasibility and case-control studies published so far suggest comparable indicators of radicality, such as the number of dissected lymph nodes, but also demonstrate potential advantages like a lower intra-operative blood loss, shorter hospital stay and lower postoperative complication rate in comparison with the conventional approach.

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Unlabelled: Endometrial carcinoma is the most common genital cancer in women. While patients usually present with vaginal bleeding, in 10-20% this characteristic symptom is absent. Endometrial thickness (double layer) is measured by transvaginal sonography and thickening indicates an increased risk of malignancy or other pathology (hyperplasia or polyps).

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Radiation-induced genomic instability, in which the progeny of irradiated cells display a high frequency of nonclonal genomic damage, occurs at a frequency inconsistent with mutation. We investigated the mechanism of this nontargeted effect in human mammary epithelial cells (HMEC) exposed to low doses of radiation. We identified a centrosome-associated expression signature in irradiated HMEC and show here that centrosome deregulation occurs in the first cell cycle after irradiation, is dose dependent, and that viable daughters of these cells are genomically unstable as evidenced by spontaneous DNA damage, tetraploidy, and aneuploidy.

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Study Objective: In this study we investigated whether teaching advanced laparoscopic procedures like laparoscopic-assisted surgical staging (LASS) for endometrial cancer negatively affects the learning curve of the attending surgeon.

Design: Retrospective study (Canadian Task Force classification II-3.)

Setting: Department of Obstetrics and Gynecology, University of Arizona, Tucson.

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Centrosomes are small organelles that organize the mitotic spindle during cell division and are also involved in cell shape and polarity. Within epithelial tumors, such as breast cancer, and some hematological tumors, centrosome abnormalities (CAs) are common, occur early in disease etiology, and correlate with chromosomal instability and disease stage. In situ quantification of CA by optical microscopy is hampered by overlap and clustering of these organelles, which appear as focal structures.

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Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary glands. This review will address the role of TGF-beta in regulating hormone-dependent proliferation and morphogenesis.

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Objective: With the present study we wanted to evaluate the effect of a radical resection of bowel and bladder endometriosis with respect to relief of pain symptoms and long-term effects.

Study Design: Retrospectively we analyzed 23 patients undergoing bowel or bladder resection for infiltrating endometriosis between 1995 and 2004. Chart review was performed and data were analyzed with respect to pain symptoms, fertility, type of surgery, operative morbidity and mortality.

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Objective: In this analysis, we summarize our experiences with the laparoscopic parametrectomy/upper vaginectomy (LPUV) as a treatment option for patients with an unexpected finding of cervical cancer after simple hysterectomy as well as for patients with cancer of the vaginal cuff.

Methods: From 1995-2004, 6 of our patients underwent LPUV including 5 patients with stage Ib(1) cervical cancer and one patient with Ia(1) cervical cancer. Prior procedures were TVH (n = 3), TAH (n = 2) or LAVH (n = 1).

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