Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Abstract: PURPOSE: Advances in genetics and increased public awareness increased the demand for interdisciplinary genetic outpatient consultation (IOGC). Communicating cancer risk is complex, and ideally information transfer should be individualized. Although psychological experiences with genetic testing have been studied in detail, studies on long-term experiences with IOGC and information transfer are lacking. We assessed patients' understanding and satisfaction with IOGC in families at risk of hereditary breast and ovarian cancer (HBOC) with the aim of informing best clinical practice, improving compliance and informed decision-making. METHODS: Female counselees referred for IOGC between July 1, 2009 and July 1, 2011 were eligible. Data were collected using a 47-item postal questionnaire to assess sociodemographic, psychological, behavioral parameters. Overall satisfaction and personal usefulness of IOGC were assessed with a five-point, and risk perception with a visual analog scale. Data were analyzed using Spearman rank, Wilcoxon U or Chi-squared test. RESULTS: 612 (72 %) of 849 women participated reported being highly satisfied (75 %, n = 430) and declared personal usefulness (73 %, n = 421) on average 3.5 years after IOGC. Women deemed "high risk" assessed their risk of developing BC as significantly higher than non-high-risk counselees (3.2 versus 3.0, p = 0.00484). Risk perception was lower in BRCA1/2 mutation carriers than in women with unclassified variants or no mutation (2.8 versus 3.5 and 3.1, respectively). CONCLUSION: Women with an HBOC background have additional needs to achieve long-term satisfaction after IOGC. Prospective studies are required to optimize care for the increasing number of people who seek genetic consultation, particularly as the complexity of genetics knowledge increases.
    Type of Publication: Journal article published
    PubMed ID: 27282618
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Abstract: INTRODUCTION: Lynch syndrome is known by healthcare providers mainly for patients with colorectal cancer. Awareness of other associated tumors, such as endometrial or ovarian cancer, is low. This study aimed to analyze the prevalence of Lynch syndrome in unselected patients with endometrial or ovarian cancer. In addition, the willingness of patients and family members to undergo germline mutation testing was investigated. METHODS: The medical records of all patients diagnosed with endometrial or ovarian cancer at the Department of Gynecology and Obsterics, University Hospital Dresden, between 1998 and 2012, were screened for a family history of HNPCC-associated cancer. Telephone interviews were used to screen, inform, and enroll patients in this genetic analysis study. Molecular analysis was performed by prescreening of tumor tissue, followed by germline mutation analysis. RESULTS: Two hundred and eighty-three patients were diagnosed with endometrial cancer, 291 with ovarian cancer, and 14 with both. A positive family history for tumors associated with Lynch syndrome was documented for 61 patients. Two pathogenic mutations in the genes MLH1 and MSH2 in nine genetic analyses had already been detected before. After genetic counseling, only 10 of 31 index patients (32.3 %) consented for mutation analysis. However, no additional pathogenic heterozygous mutations were found. CONCLUSION: In this retrospective cohort study in unselected patients with endometrial or ovarian cancer, only a small number of patients with suspected Lynch syndrome could be identified. Of those, acceptance of germline analyses was moderate, only. As a result, the rate of identified pathogenic germline mutations was lower than expected. Therefore, we are convinced that more information on cancer risks, options for predictive molecular testing and preventive procedures, needs to be provided to patients and gynecologists.
    Type of Publication: Journal article published
    PubMed ID: 27535758
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Abstract: PURPOSE: EpCAM is overexpressed in many neoplasms including ovarian cancer. We screened the EpCAM-coding gene TACSTD1 for single nucleotide polymorphisms (SNPs), which could alter ovarian cancer risk, impact upon disease progression, or alter binding of the therapeutic EpCAM-binding antibody, catumaxomab. METHODS: DNA fragments of 10 healthy volunteers were analyzed to identify SNPs. Subsequently, DNA of ovarian cancer patients (n = 117) and age-matched healthy controls (n = 115) was genotyped by restriction fragment length polymorphism and pyrosequencing. TACSTD1 genotypes 4461T〉C were cloned into a gene expression vector; Hek293 cells were subsequently used for stable transfection. FACS analysis of the transfected Hek293 cells was conducted with HO-3-the EpCAM binding site of catumaxomab-to determine antibody binding. RESULTS: One SNP was detected in exon 3 (4461T〉C; rs1126497), resulting in an amino acid exchange at position 115 (Met115Thr). Another polymorphism was found in the 3'UTR (17225A〉G; rs1421). Genotyping of patients and controls for these SNPs did not reveal significant differences in genotype distribution. Regarding 17225A〉G, the homozygous AA-genotype was associated with diminished progression-free survival (PFS; p = 0.032). Overall survival, FIGO-stage, grading, and age did not differ significantly between genotypes. FACS analysis of transfected Hek293 cells overexpressing EpCAM 115Met/Thr showed binding of HO-3 to both proteins. CONCLUSIONS: The AA-genotype of 17225A〉G seems to be associated with diminished PFS in ovarian cancer patients. The amino acid exchange resulting from 4461T〉C does not appear to alter binding of HO-3, suggesting that treatment with catumaxomab can be offered to patients regardless of their TACSTD1-genotype.
    Type of Publication: Journal article published
    PubMed ID: 26115884
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Abstract: BACKGROUND: Determination of mutation status of BRCA1 and BRCA2 has become part of the clinical routine. However, the spectrum of genetic variants differs between populations. The aim of this study was to deliver a comprehensive description of all detected variants. METHODS: In families fulfilling one of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) criteria for genetic testing, one affected was chosen for analysis. DNA of blood lymphocytes was amplified by PCR and prescreened by DHPLC. Aberrant fragments were sequenced. All coding exons and splice sites of BRCA1 and BRCA2 were analyzed. Screening for large rearrangements in both genes was performed by MLPA. RESULTS: Of 523 index patients, 121 (23.1%) were found to carry a pathogenic or likely pathogenic (class 4/5) mutation. A variant of unknown significance (VUS) was detected in 73/523 patients (13.9%). Two mutations p.Gln1756Profs*74 and p.Cys61Gly comprised 42.3% (n = 33/78) of all detected pathogenic mutations in BRCA1. Most of the other mutations were unique mutations. The most frequently detected mutation in BRCA2 was p.Val1283Lys (13.9%; n = 6/43). Altogether, 101 different neutral genetic variants were counted in BRCA1 (n = 35) and in BRCA2 (n = 66). CONCLUSION: The two most frequently detected mutations are founder mutations in Poland and Czech Republic. More similarities seem to be shared with our direct neighbor countries compared to other European countries. For comparison of the extended genotype, a shared database is needed.
    Type of Publication: Journal article published
    PubMed ID: 28324225
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Abstract: BACKGROUND: Some women of families at high risk of breast cancer (BC) choose prophylactic mastectomy (PM) in spite of ambiguous evidence for survival benefits. The aim of this study was to investigate counselees' characteristics, decisions on PM, and frequencies of different procedures to better understand how to tailor interventions. PATIENTS AND METHODS: Eight hundred and forty-nine counselees who attended interdisciplinary consultation for genetic risk adjustment at the University Hospital Heidelberg between July 2009 and July 2011 received a tripartite questionnaire addressing sociodemographic characteristics, psychological parameters, behavioural questions, and medical data. RESULTS: Six hundred and twelve of the 849 counselees (72%) returned the questionnaire. Four hundred were classified as high risk of genetic BC (19.5% BRCA mutation carriers; 4% unclassified variant (UV); and 76.5% calculated as high risk by pedigree). Two hundred and thirteen out of 400 (53%) were diagnosed with BC. Fourteen out of 54 (27%) BRCA mutation carriers with BC chose contralateral PM (CPM) compared to 24/126 (14%) without a mutation but with a personal BC history (p = 0.2175). Of those without BC, 12/27 (44%) mutation carriers opted for bilateral PM (BPM) compared to none without a mutation (p 〈 0.0001). Women who received any PM (CPM and BPM) reported a higher emotional burden from partners (p = 0.003) and family (p = 0.008), more worries regarding children and family (p = 0.003) and were associated with positive mutation status and higher heterozygous and lifetime risk (all p 〈 0.001). CONCLUSION: Although evidence on survival benefit is unclear in several clinical situations, a relevant number of counselees opt for PM. Counselees may decide based on other reasons than survival benefit.
    Type of Publication: Journal article published
    PubMed ID: 28439664
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Abstract: INTRODUCTION: Prognosis of Her2-positive breast cancer has changed since the introduction of trastuzumab for treatment in metastatic and early breast cancer. It was described to be even better compared to prognosis of Her2-negative metastatic breast cancer. The purpose of this study was to evaluate the effect of trastuzumab in our cohort. Besides the effect of adjuvant pretreatment with trastuzumab on survival of patients with metastatic Her2-positive breast cancer was analyzed. METHODS: All patients with primary breast cancer of the Regional Breast Cancer Center Dresden diagnosed during the years 2001-2013 were analyzed for treatment with or without trastuzumab in the adjuvant and in the metastatic treatment setting using Kaplan-Meier survival estimation and Cox regression. Age and tumor stage at time of first diagnosis of breast cancer as well as hormone receptor status, grading, time, and site of metastasis at first diagnosis of distant metastatic disease were analyzed. RESULTS: Of 4.481 female patients with primary breast cancer, 643 presented with metastatic disease. Her2-positive status was documented in 465 patients, including 116 patients with primary or secondary metastases. Median survival of patients with Her2-positive primary metastatic disease was 3.0 years (95% CI 2.3-4.0). After adjustment for other factors, survival was better in patients with Her2-positive breast cancer with trastuzumab therapy compared to Her2-negative metastatic disease (HR 2.10; 95% CI 1.58-2.79). Analysis of influence of adjuvant therapy with and without trastuzumab by Kaplan-Meier showed a trend for better survival in not pretreated patients. Median survival was highest in hormone receptor-positive Her2-positive (triple-positive) primary metastatic breast cancer patients with 3.3 years (95% CI 2.3-4.6). CONCLUSION: Prognosis of patients with Her2-positive metastatic breast cancer after trastuzumab treatment is more favorable than for Her2-negative breast cancer. The role of adjuvant chemotherapy with or without trastuzumab warrants further research. Survival is best in triple-positive metastatic breast cancer. This will effect counseling at the time of first diagnosis of metastatic breast cancer.
    Type of Publication: Journal article published
    PubMed ID: 28616827
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Abstract: OBJECTIVE: Ovarian cancer is the fifth most common cancer in women and one of the leading causes of death from gynecological malignancies. Despite of its clinical importance, ovarian tumorigenesis is poorly understood and prognosis remains poor. This is particularly true for the most common type of ovarian cancer, high-grade serous ovarian cancer. RESULTS: Two models are considered, whether it arises from the ovarian surface epithelium or from the fallopian tube. The first model is based on (1) the pro-inflammatory environment caused by ovulation events, (2) the expression pattern of ovarian inclusion cysts, and (3) biomarkers that are shared by the ovarian surface epithelium and malignant growth. The model suggesting a non-ovarian origin is based on (1) tubal precursor lesions, (2) genetic evidence of BRCA1/2 mutation carriers, and (3) recent animal studies. Neither model has clearly demonstrated superiority over the other. Therefore, one can speculate that high-grade serous ovarian cancer may arise from two different sites that undergo similar changes. Both tissues are derived from the same embryologic origin, which may explain how progenitor cells from different sites can respond similar to stimuli within the ovaries. However, distinct molecular drivers, such as BRCA deficiency, may still preferentially arise from one site of origin as precancerous mutations are frequently seen in the fallopian tube. CONCLUSIONS: Confirming the origin of ovarian cancer has important clinical implications when deciding on cancer risk-reducing prophylactic surgery. It will be important to identify key biomarker to uncover the sequence of ovarian tumorigenesis.
    Type of Publication: Journal article published
    PubMed ID: 28940023
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1432-0711
    Keywords: umbilical cord artery ; oxygen induced constriction ; vasodilatatory pharmaca
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wurde die Wirkung verschiedener gefäßerweiternder Pharmaka auf die sauerstoffbedingte Vasokonstriktion der isolierten und künstlich perfundierten menschlichen Nabelschnurarterie untersucht. Dabei zeigte sich: 1. die sauerstoffbedingte Konstriktion kann durch Glyceryl-Trinitrat (2 μg/ ml) verhindert und aufgehoben werden 2. Methysergid kann die O2-Wirkung weder unterbinden noch beseitigen, unterdrückt aber vollständig eine durch Serotonin (5-OH-Tryptamin; 10μg/ml) hervorgerufenen Vasokonstriktion 3. Phentolamin, Tolazolin und Propranolol haben keinen Einfluß auf die sauerstoffbedingte Konstriktion. Sie können auch die geringe, durch Norepinephrin verursachte Gefäßverengung nicht verhindern. 4. Isproterenol und Buphenin beeinflussen den Gefäßwiderstand der isolierten Nabelschnurarterie nicht.
    Notes: Summary The effect of various vasodilating pharmaca on the oxygen induced vasoconstriction of the isolated, artificially perfused human umbilical cord artery is investigated. It is demonstrated that: 1. the oxygen induced constriction can be prevented and abolished by glyceryl-trinitrate (2μg/ml) 2. Methysergid neither abolishes nor prevents the oxygen induced vasoconstriction though the serotonine (5-OH-tryptamine) induced constriction (10μg/ml) is completely suppressed 3. phentolamine, tolazoline and propranolol do not affect the O2-induced contraction. These sympathicolytic agents cannot hinder the slight constriction caused by norepinephrine 4. isoproterenol and buphenine do not influence the vascular resistance of the umbilical cord artery.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...