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1.
Geburtshilfe Frauenheilkd ; 83(8): 919-962, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37588260

RESUMO

Summary 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. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat women with endometrial cancer of low risk prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 1 of this short version of the guideline provides recommendations on epidemiology, screening, diagnosis, and hereditary factors. The epidemiology of endometrial cancer and the risk factors for developing endometrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer. The use of geriatric assessment is considered and existing structures of care are presented.

2.
Breast Care (Basel) ; 17(2): 121-128, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35702498

RESUMO

Purpose: Classical type of lobular neoplasia (LN) encompassing both atypical lobular hyperplasia and classical lobular carcinoma in situ of the breast is a lesion with uncertain malignant potential and has been the topic of several studies with conflicting outcome results. The aim of our study was to clarify outcome-relevant factors and treatment options of classical LN. Methods: We performed a pathological re-evaluation of the preoperative biopsy specimens and a retrospective clinical and radiological data analysis of 160 patients with LN from the Breast Center Zurich. Open surgery was performed in 65 patients, vacuum-assisted biopsy (VAB) in 79 patients, and surveillance after breast core needle biopsy (CNB) in 16 patients. Results: The upgrade rate into ductal carcinoma in situ/invasive cancer was the highest in case of imaging/histology discordance (40%). If the number of foci in the biopsy specimen was ≥3, the upgrade rate in the consecutive surgical specimens was increased (p = 0.01). The association of classical LN with histological microcalcification correlated with shortened disease-free survival (p < 0.01), whereas other factors showed no impact on follow-up. Conclusions: Surveillance or subsequent VAB after CNB of LN is sufficient in most cases. Careful consideration of individual radiological and histological factors is required to identify patients with a high risk of upgrade into malignancy. In those cases, surgical excision is indicated.

3.
Eur J Cancer Prev ; 31(2): 152-157, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33899749

RESUMO

BACKGROUND: Diagnostic delay of breast cancer related to the false-negative assessment of the healthcare provider leads to tumor progression and might worsen the outcome. Previous studies found some factors associated with provider-related diagnostic delay; however, tumor biology has tended not to be considered. The aim of our study was to find differences in diagnostic delay of poorly differentiated breast cancer types. METHODS: Data of 970 patients with newly diagnosed moderately/poorly differentiated (G2/3) breast cancer at the age ≥40 years was retrospectively analyzed regarding breast cancer type, diagnostic delay and its consequence, clinical factors and physician's assessment. Multivariate analysis was used to evaluate associated factors with diagnostic delay. RESULTS: We observed a diagnostic delay in 3.8% (n = 37) of all patients. Mean delay time was 128 days, and clinically relevant tumor growth was observed in 43.2% of these cases. Delay was significantly higher in the group of triple-negative breast cancer (9.9% versus 2.7, 5.3 and 1.8% in hormonal receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR-/Her2+ and HR+/Her2+, respectively; P value <0.001). Age, breast density and reason for presentation were not correlated to diagnostic delay. CONCLUSION: Patients with triple-negative breast cancer are at higher risk of receiving a false-negative assessment and experiencing a diagnostic delay. Our results emphasize the importance of a detailed consideration of clinical risk factors and provider training and suggest a broad indication for a core needle biopsy.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Adulto , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Diagnóstico Tardio , Feminino , Humanos , Receptor ErbB-2 , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/epidemiologia
4.
Geburtshilfe Frauenheilkd ; 81(4): 447-468, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33867563

RESUMO

Purpose 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. The consensus on recommendations and statements was achieved in a structured consensus process. Method The current guideline is based on the expired S1-guideline, which was updated by a systematic search of the literature and a review of relevant publications issued between February 2014 and March 2019. Statements were compiled and voted on by a panel of experts. Recommendations The guideline provides general and specific recommendations on the prevention, diagnosis and treatment of positioning injuries.

5.
Int J Gynecol Cancer ; 30(10): 1589-1594, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32817308

RESUMO

INTRODUCTION: The daily clinical routine in the operating room includes patient positioning. The number of perioperative positioning-related complications is growing, along with the legal proceedings concerning this topic, and only a few guidelines exist to provide specific recommendations. The aim of this survey was to assess perioperative positioning and associated adverse events during gynecological cancer surgery in Germany. METHODS: A total of 633 gynecological departments of primary, secondary, and maximum healthcare hospitals in Germany were invited to participate in this multiple-choice online questionnaire. The survey was conducted anonymously for a period of six months. The survey was divided into five different sections: descriptive information about the respondent department, pre- and postoperative management, management of positioning in the operating room based on two fictional case examples, and quality management. RESULTS: The response rate of our survey was 29.1 % (184/633). Nearly half of the departments (46.7 %) reported to have had one to five patients with positioning-related complications during the prior 12 months, and 29.1 % had experienced a legal dispute due to positioning-related complications. Departments with more than 50 gynecologic-oncological surgeries per year more often reported positioning-related complications (p=0.003). Standard operating procedures exist in almost every department for laparoscopic (97 %) and open surgery (95.1 %), respectively. DISCUSSION: The high number of positioning-related complications throughout all departments of different healthcare levels underlines the relevance of this issue and supports the need for a prospective European registry for further analysis. Training and education for all staff members should be routinely implemented to reduce and prevent positioning-related complications.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Posicionamento do Paciente/normas , Complicações Pós-Operatórias/etiologia , Feminino , Alemanha , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/normas , Humanos , Posicionamento do Paciente/efeitos adversos , Assistência Perioperatória/normas , Complicações Pós-Operatórias/prevenção & controle , Inquéritos e Questionários
6.
Cancers (Basel) ; 12(9)2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32854222

RESUMO

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. Germline variants and somatic events may act in concert to modulate the molecular evolution of the tumor, where mismatch-repair deficiency is common in endometrioid endometrial tumors whereas homologous recombinational repair deficiency has been described for non-endometrioid endometrial tumors. In this review, we will survey the currently known genomic predispositions for endometrial cancer and discuss their relevance for clinical management in terms of counseling, screening and novel treatments.

7.
Anticancer Res ; 40(4): 2125-2131, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234905

RESUMO

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) can be divided into subtypes of basal-like (BL), mesenchymal-like (ML), luminal androgen receptor (LAR), and immunomodulatory (IM). The aim of our study was to assess whether there are distinct radiologic features within the different TNBC subtypes and whether this has potential clinical impact. PATIENTS AND METHODS: Imaging pictures of 135 patients with TNBC were re-evaluated. TNBC subtyping was performed on asservated tumor tissue using a panel of antibodies. RESULTS: Mammographic margins of LAR-TNBC were more often spiculated (24.3% versus 0-4.1%). BL-TNBC presented more frequent a mass without calcification in mammogram than other subtypes (71.4% versus 48.6-57.9%). In ultrasound, ML and LAR were described more often with smooth borders. CONCLUSION: The histopathological subtype of TNBC influences its presentation in ultrasound and mammogram. This can reflect a different growth pattern of the subtypes and may have an impact on the early diagnosis of TNBC.


Assuntos
Biomarcadores Tumorais/genética , Mamografia/métodos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Adulto , Proliferação de Células/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Receptores Androgênicos/genética , Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
8.
Angew Chem Int Ed Engl ; 59(14): 5771-5781, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-31863711

RESUMO

Designed peptides derived from the islet amyloid polypeptide (IAPP) cross-amyloid interaction surface with Aß (termed interaction surface mimics or ISMs) have been shown to be highly potent inhibitors of Aß amyloid self-assembly. However, the molecular mechanism of their function is not well understood. Using solution-state and solid-state NMR spectroscopy in combination with ensemble-averaged dynamics simulations and other biophysical methods including TEM, fluorescence spectroscopy and microscopy, and DLS, we characterize ISM structural preferences and interactions. We find that the ISM peptide R3-GI is highly dynamic, can adopt a ß-like structure, and oligomerizes into colloid-like assemblies in a process that is reminiscent of liquid-liquid phase separation (LLPS). Our results suggest that such assemblies yield multivalent surfaces for interactions with Aß40. Sequestration of substrates into these colloid-like structures provides a mechanistic basis for ISM function and the design of novel potent anti-amyloid molecules.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Fragmentos de Peptídeos/antagonistas & inibidores , Peptídeos/química , Sequência de Aminoácidos , Peptídeos beta-Amiloides/metabolismo , Microscopia de Fluorescência , Simulação de Dinâmica Molecular , Ressonância Magnética Nuclear Biomolecular , Fragmentos de Peptídeos/metabolismo , Peptídeos/metabolismo , Especificidade por Substrato
9.
BMC Pregnancy Childbirth ; 18(1): 435, 2018 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-30390639

RESUMO

BACKGROUND: Stress and anxiety during pregnancy and childbirth have negative consequences for both mother and child. There are indications that music has a positive effect in this situation. The present study investigates the influence of music during the caesarean on anxiety and stress of the expectant mother. METHODS: The SAMBA study is a single-centre, controlled, randomized study including 304 patients. Women in the intervention group heard music via loudspeakers from one of four self-selected genres. The control group had standard treatment without music. The caesarean was performed in regional Anesthesia. At admission, at skin incision, during skin suture and two hours after completion of surgery, different subjective (State-Trait Anxiety Inventory, visual analogue scale for anxiety) and objective parameters (salivary cortisol/amylase, heart rate, blood pressure) were collected. Mixed-factorial Analysis of variances as well as independent sample t-tests were applied for data analysis. RESULTS: At skin suture, significantly lower anxiety levels were reported in the intervention group regarding State anxiety (31.56 vs. 34.41; p = .004) and visual analogue scale for anxiety (1.27 vs. 1.76; p = .018). Two hours after surgery, the measured visual analogue scale for anxiety score in the intervention group was still significantly lower (0.69 vs. 1.04; p = .018). The objective parameters showed significant differences between the groups in salivary cortisol increase from admission to skin suture (12.29 vs. 16.61 nmol/L; p = .043), as well as systolic blood pressure (130.11 vs. 136.19 mmHg; p = .002) and heart rate (88.40 vs. 92.57/min; p = .049) at skin incision. CONCLUSIONS: Music during caesarean is an easy implementable and effective way of reducing stress and anxiety of the expectant mother. TRIAL REGISTRATION: German registry for clinical trials ( DRKS00007840 ). Registered 16/06/2015. Retrospectively registered.


Assuntos
Ansiedade/terapia , Cesárea/psicologia , Musicoterapia/métodos , Complicações do Trabalho de Parto/terapia , Estresse Psicológico/terapia , Adolescente , Adulto , Ansiedade/etiologia , Ansiedade/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Complicações do Trabalho de Parto/etiologia , Complicações do Trabalho de Parto/psicologia , Parto/psicologia , Gravidez , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Resultado do Tratamento , Adulto Jovem
10.
Elife ; 62017 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-29148426

RESUMO

Membrane-assisted amyloid formation is implicated in human diseases, and many of the aggregating species accelerate amyloid formation and induce cell death. While structures of membrane-associated intermediates would provide tremendous insights into the pathology and aid in the design of compounds to potentially treat the diseases, it has not been feasible to overcome the challenges posed by the cell membrane. Here, we use NMR experimental constraints to solve the structure of a type-2 diabetes related human islet amyloid polypeptide intermediate stabilized in nanodiscs. ROSETTA and MD simulations resulted in a unique ß-strand structure distinct from the conventional amyloid ß-hairpin and revealed that the nucleating NFGAIL region remains flexible and accessible within this isolated intermediate, suggesting a mechanism by which membrane-associated aggregation may be propagated. The ability of nanodiscs to trap amyloid intermediates as demonstrated could become one of the most powerful approaches to dissect the complicated misfolding pathways of protein aggregation.


Assuntos
Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Agregados Proteicos , Multimerização Proteica , Humanos , Espectroscopia de Ressonância Magnética , Membranas/química , Dobramento de Proteína
11.
Oncotarget ; 8(20): 32461-32475, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-28427147

RESUMO

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. BRCA1 depletion stabilizes HMMR abundance and disrupts cortical asymmetry of NUMA-dynein complexes in dividing cells such that polarity cues provided by cell-matrix adhesions were not able to orient division. We also show that immortalized mammary cells carrying a mutant BRCA1 allele (BRCA1 185delAG/+) reproduce many of these effects but in this model, oriented divisions were maintained through cues provided by CDH1+ cell-cell junctions. These findings reveal a previously unknown effect of BRCA1 suppression on mechanisms that regulate the cell division axis in proliferating, non-transformed human mammary epithelial cells and consequent downstream effects on the mitotic integrity and phenotype control of their progeny.


Assuntos
Proteína BRCA1/metabolismo , Neoplasias da Mama/genética , Proteína BRCA1/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Células Epiteliais/patologia , Feminino , Células HeLa , Humanos , Fenótipo , Ploidias
12.
Cell Cycle ; 13(14): 2248-61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24875404

RESUMO

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. Silencing of RHAMM delays the kinetics of spindle assembly, mislocalizes targeting protein for XKlp2 (TPX2), and attenuates the localized activation of Aurora kinase A with a consequent reduction in mitotic spindle length. The RHAMM-TPX2 complex requires a C-terminal basic leucine zipper in RHAMM and a domain that includes the nuclear localization signal in TPX2. Together, our findings identify RHAMM as a critical regulator for Aurora kinase A signaling and suggest that RHAMM ensures bipolar spindle assembly and mitotic progression through the integration of biochemical and structural pathways.


Assuntos
Aurora Quinase A/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Receptores de Hialuronatos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Nucleares/metabolismo , Fuso Acromático/enzimologia , Aurora Quinase A/genética , Proteínas de Ciclo Celular/genética , Ativação Enzimática , Proteínas da Matriz Extracelular/genética , Células HeLa , Humanos , Receptores de Hialuronatos/genética , Cinética , Proteínas Associadas aos Microtúbulos/genética , Mitose , Proteínas Nucleares/genética , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estabilidade Proteica , Transporte Proteico , Interferência de RNA , Transdução de Sinais , Transfecção
13.
Langenbecks Arch Surg ; 399(3): 343-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24515267

RESUMO

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. In addition, cases anonymously reported to the Expert Committee for Medical Malpractice Claims of the Medical Association of North Rhine between 2002 and 2012 were analyzed. MAIN OUTCOME MEASURE: Incidence of acute CS after gynecological operations. RESULTS: A total of 59 questionnaires (35 %) were returned for analysis, reporting 21 cases of CS. Based on the collected data, we calculated an incidence of postoperative CS ranging between 0.067 % and 0.28 %. All reported cases of postoperative CS occurred after surgeries in lithotomy position, 57.1 % of cases occurred after laparoscopic procedures and 76.2 % after procedures longer than 4 h. Overall, 61.0 % of departments do not routinely inform about the risk of this complication when they get patients' informed consent. Reported prevention strategies were inconsistent and ranged from none to multiple measures. CONCLUSION: CS is a complication clearly associated with long lasting gynecological operations in Lithotomy position. Despite a relatively high incidence, so far no guidelines on perioperative management and medicolegal aspects exist and preventive measures are heterogeneous among institutions. The need for guidelines and recommendations by an expert committee has been identified.


Assuntos
Síndromes Compartimentais/epidemiologia , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Extremidade Inferior , Doença Aguda , Adulto , Idoso , Feminino , Alemanha , Humanos , Incidência , Laparoscopia/efeitos adversos , Pessoa de Meia-Idade , Duração da Cirurgia , Posicionamento do Paciente/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
14.
Eur J Obstet Gynecol Reprod Biol ; 173: 7-12, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24290432

RESUMO

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. The type of leg support and the intraoperative hypotension have been discussed as risk factors but evidence is mainly based on case reports and expert opinion. Studies suggest that time spent in the LT position and the addition of head-down tilt are associated with CS. As these positions are routinely applied during various gynecologic procedures, forensically CS has to be considered as a specific complication of gynecologic surgery in the LT position. Despite the low incidence there is a need for prospective studies and guidelines for its prevention. Sixteen case reports describing 19 cases of CS following gynecologic surgery in lithotomy position were found during a literature search. This review is based on 14 of these case reports (17 cases), which describe a postoperative compartment syndrome in a previously healthy leg. We summarize the reported cases and literature on CS after gynecologic procedures in order to increase awareness among medical staff and to give careful recommendations regarding perioperative management based on available information.


Assuntos
Síndromes Compartimentais/etiologia , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Posicionamento do Paciente/efeitos adversos , Feminino , Humanos
15.
Oncol Lett ; 3(3): 530-534, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22740945

RESUMO

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. The study was performed in an orthotopic murine model of peritoneal disseminated platin-resistant ovarian cancer. Mice were treated with bevacizumab and/or paclitaxel or buffer (control). Reduction of body surface and increased survival rates were assessed as therapeutic success. Survival of mice in all treatment groups was significantly enhanced when compared to the non-treatment control group. The combination of paclitaxel plus bevacizumab significantly improved body surface as well as overall survival in comparison to a treatment with only one of the drugs. Treatment of malignant effusion with a single dose of bevacizumab as an intraperitoneal application, with or without cytostatic co-medication, may be a powerful alternative to systemic treatment.

16.
J Cancer Res Clin Oncol ; 138(4): 603-10, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22209976

RESUMO

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. Combinations of Ad5/3MDR1E1 and cytostatic agents were studied in vivo and in vitro. An in vivo hepatotoxicity model was used to evaluate liver toxicity. RESULTS: We demonstrate efficient oncolysis of Ad5/3MDR1E1 in chemotherapy-resistant ovarian cancer cells as well as therapeutic efficacy in an orthotopic mouse model. Further, combining Ad5/3MDR1E1 with paclitaxel resulted in greater therapeutic benefit than either agent alone. CONCLUSION: These preclinical data suggest that a fiber-modified adenovirus vector under the control of the MDR1 promoter represents a promising treatment strategy for platinum-pretreated ovarian cancer as a single agent or in combination with conventional anticancer drugs.


Assuntos
Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/fisiologia , Neoplasias Ovarianas/terapia , Paclitaxel/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Adenoviridae/genética , Adenoviridae/fisiologia , Animais , Antineoplásicos/farmacologia , Proteínas do Capsídeo/genética , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Cisplatino/farmacologia , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Vírus Oncolíticos/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/virologia , Regiões Promotoras Genéticas/genética , Análise de Sobrevida , Resultado do Tratamento , Replicação Viral , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Case Rep Neurol ; 3(1): 54-61, 2011 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-21490714

RESUMO

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. The histological appearance was identical to a uterine tumor the patient was treated for with hysterectomy 16 years before. The metastases were removed surgically, and after 3 months ataxia had regressed. We conclude that the presenting cerebellar degeneration in this patient resulted from the metastatic recurrence of the endometrial tumor.

18.
J Minim Invasive Gynecol ; 18(1): 81-4, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21094098

RESUMO

STUDY OBJECTIVE: The aim of this study was to estimate the benefit of excision of the endocervix during laparoscopic supracervical hysterectomy (LSH) with regard to postoperative cyclical bleeding. DESIGN: Cohort study from 2 centers (Canadian Task Force classification II-2). SETTING: Two surgical teams at the University of Duesseldorf Medical Center and PAN Clinic, Cologne, Germany. PATIENTS: Women with menstrual bleeding disorders resistant to medical treatment, symptomatic leiomyomata, dysmenorrhea. INTERVENTION: Laparoscopic supracervical hysterectomy. The uterus was transsected from the cervix with 2 techniques with and without excision of cervical canal. MEASUREMENTS AND MAIN RESULTS: We evaluated 300 patients who underwent consecutive LSH procedures. In 150 patients the uterus was transsected from the cervix using a monopolar loop. In a second series of 150 patients a unipolar needle electrode was used for the uterine amputation and the excision of cervical canal. The mean duration of the transsection was 65 seconds (monopolar loop) versus 168 seconds (monopolar needle). The excision of the endocervix was performed without any complications in 148 procedures. Histologic examination of the removed tissue revealed endocervical tissue in 83.3% (n = 125), endometrium in 9.4% (n = 14), cervicoisthmic mucosa in 3.3% (n = 5), and myometrium only in 4% (n = 4). All 300 patients were contacted 12 months after surgery to inquire about bleeding status, and 282 (94%) responded. In patients who underwent excision of the endocervix, postoperative cyclical bleeding was significantly reduced compared with the control group (1.4% vs 10.7%). CONCLUSION: The results of this study indicate that the routine excision of the endocervix is a quick safe procedure which allows a significant reduction of postoperative cyclical bleeding in patients who undergo LSH.


Assuntos
Histerectomia/efeitos adversos , Laparoscopia/métodos , Distúrbios Menstruais/etiologia , Metrorragia/etiologia , Adulto , Feminino , Humanos , Histerectomia/métodos , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Gynakol Geburtshilfliche Rundsch ; 49(3): 117-25, 2009.
Artigo em Alemão | MEDLINE | ID: mdl-19525618

RESUMO

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. Regarding long-term survival, reliable data from prospective randomized studies are still lacking but can be expected to be available in the near future.


Assuntos
Neoplasias dos Genitais Femininos/secundário , Neoplasias dos Genitais Femininos/cirurgia , Laparoscopia/tendências , Excisão de Linfonodo/métodos , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Metástase Linfática
20.
Maturitas ; 62(2): 176-8, 2009 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-19121901

RESUMO

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). OBJECTIVE: We sought to correlate hysteroscopic and pathological findings in asymptomatic postmenopausal women with sonographically thickened endometrium (>6mm). STUDY DESIGN: A prospective observational study in a university hospital of 304 postmenopausal women referred between 1996 and 2006 because of a sonographically thickened endometrium in the absence of abnormal bleeding, who underwent continuous flow hysteroscopy (4.5mm Storz hysteroscope) and fractionated curettage of the uterine cervix and corpus (D & C) in addition to vaginal sonography (5MHz probe). RESULTS: The mean age of the women was 64.8 (range 57.7-71.9) years. Average endometrial thickness measured by ultrasound was 12mm+/-6.7mm. Hysteroscopy suggested the presence of endometrial polyps in 226 women (74.3%), simple endometrial hyperplasia in 34 (11.2%), atrophic endometrium in 18 (5.9%), complex endometrial hyperplasia in 2 (0.7%), atypical hyperplasia in 3 (1%) and leiomyoma in 9 (3.0%). In 12 women (3.9%), the hysteroscopic appearance suggested malignancy and histology revealed endometrial adenocarcinoma. All hysteroscopic results were confirmed by histological examination. CONCLUSION: Hysteroscopy represents an easy, safe and effective method for the investigation of asymptomatic women with a thickened endometrium found with transvaginal ultrasound. The commonest pathology was endometrial polyps.


Assuntos
Hiperplasia Endometrial/diagnóstico , Neoplasias do Endométrio/diagnóstico , Histeroscopia , Neoplasias Uterinas/diagnóstico , Idoso , Atrofia/diagnóstico , Hiperplasia Endometrial/patologia , Endométrio/diagnóstico por imagem , Endométrio/patologia , Feminino , Humanos , Histeroscopia/métodos , Leiomioma/diagnóstico , Pessoa de Meia-Idade , Pólipos/diagnóstico , Pós-Menopausa , Estudos Prospectivos , Fatores de Risco , Ultrassonografia , Doenças Uterinas/diagnóstico
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