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1.  Sister Mary Joseph’s nodule as the first sign of pregnancy-associated gastric cancer: A case report 
Sister Mary Joseph’s nodule is an inconspicuous and uncommon clinical sign of advanced malignant disease, especially gastric cancer. Pregnancy-associated gastric cancer is an extremely rare condition and can be difficult to diagnose, due to the absence or misinterpretation of symptoms as pregnancy-related. Diagnostic aids, such as a basic chemistry panel and imaging techniques, may not show any abnormalities. We present a case of a 37-year-old pregnant patient whose umbilical nodule was the first presenting physical sign of gastric cancer, which had metastasized throughout the abdominal and pelvic regions.
PMCID: PMC2687068  PMID: 18240358
Sister Mary Joseph’s nodule; Gastric cancer; Pregnancy-associated gastric cancer; Umbilical nodule; Metastases in pregnancy
2.  Certify it! Breast Cancer Units in Europe 
Breast Care  2009;4(4):213-217.
PMCID: PMC2941648  PMID: 20877658
3.  GPER-1 acts as a tumor suppressor in ovarian cancer 
It is known that the new membrane-bound estrogen receptor GPER-1 acts suppressive in breast cancer cells and its expression decreases during disease progression. This study was conducted to evaluate the GPER-1 expression in ovarian cancer and its correlation with progression. Its function was tested in vitro in ovarian cancer cells.
Patients and methods
GPER-1 expression was analyzed by immunohistochemistry in 35 benign ovarian tumors, 35 tumors of low-malignant potential and in 124 ovarian cancers. GPER-1 expression was correlated to the prospectively evaluated disease-free survival of ovarian cancer patients. We also tested GPER-1 expression in ovarian cancer cells and the effect of GPER-1 stimulation on cell growth.
GPER-1 expression was significantly lower in ovarian cancer tissue than in benign and low-malignant ovarian tumors. GPER-1 expression was observed in 83.1% of malignant tumors and was higher in early stage cancers and tumors with high histological differentiation. GPER-1 expression was associated with favourable clinical outcome. The difference in 2-year disease-free survival by GPER-1 expression was significant, 28.6% for GPER-1 negative and 59.2% for GPER-1 positive cases (p = 0.002). GPER-1 expression was observed in SKOV-3 and OVCAR-3 ovarian cancer cell lines. G-1, a selective GPER-1 agonist, suppressed proliferation of the two cell types via inhibition of cell cycle progression in G2/M phase and stimulation of caspase-dependent apoptosis. The blockade in G2/M phase was associated with increased expression of cyclin B1 and Cdc2 and phosphorylation of histone 3.
GPER-1 emerges as a new tumor suppressor with unsuspected therapeutic potential for ovarian cancer.
PMCID: PMC3723961  PMID: 23849542
GPR30; GPER-1; Ovarian cancer
4.  A prospective longitudinal cohort study: evolution of GERD symptoms during the course of pregnancy 
BMC Gastroenterology  2012;12:131.
Symptoms of gastro-esophageal reflux disease (GERD) in pregnancy are reported with a prevalence of 30–80%. The aim of this study was to assess the prevalence and severity of GERD symptoms during the course of pregnancy. Furthermore current practice in medical care for GERD during pregnancy was assessed.
We performed a prospective longitudinal cohort study on 510 pregnant women (mean age 28.12, SD 5.3). Investigations for reflux symptoms where based on the use of validated reflux-disease questionnaire (RDQ). Additional information was collected about the therapy. A group of non-pregnant women (mean age 24.56, SD 5.7) was included as controls. Frequency and severity of reflux symptoms were recorded in each trimester of pregnancy.
The prevalence of GERD symptoms in pregnant women increased from the first trimester with 26.1 to 36.1% in the second trimester and to 51.2% in the third trimester of pregnancy. The prevalence of GERD symptoms in the control group was 9.3%.
Pregnant women received medication for their GERD symptoms in 12.8% during the first, 9.1% during the second and 15.7% during the third trimester. Medications used >90% antacids, 0% PPI.
GERD symptoms occur more often in pregnant women than in non-pregnant and the frequency rises in the course of pregnancy. Medical therapy is used in a minority of cases and often with no adequate symptom relief.
PMCID: PMC3499455  PMID: 23006768
Gastro-esophageal reflux disease; Pregnancy; Heartburn; Regurgitation; GERD symptoms
5.  13th St. Gallen International Breast Cancer Conference 2013: Primary Therapy of Early Breast Cancer Evidence, Controversies, Consensus – Opinion of a German Team of Experts (Zurich 2013) 
Breast Care  2013;8(3):221-229.
The International Consensus Conference on the treatment of primary breast cancer takes place every two years in St. Gallen, Switzerland. The panel in St. Gallen is composed of international experts from different countries. From a German perspective, it seems reasonable to interpret the voting results in the light of AGO-recommendations and S3-guidelines for everyday practice in Germany. Consequently, a team of eight breast cancer experts, of whom two are members of the international St. Gallen panel, commented on the voting results of the St. Gallen Consensus Conference (2013). The main topics at this year's St. Gallen conference were surgical issues of the breast and axilla, radio-therapeutic and systemic treatment options, and the clinical relevance of tumour biology. The clinical utility of multigene assays for supporting individual treatment decisions was also intensively discussed.
PMCID: PMC3728634  PMID: 24415975
St. Gallen Consensus; Early breast cancer; Adjuvant therapy; Multigene signatures; Targeted therapy
6.  Endocrine Factors Modulating Immune Responses in Pregnancy 
How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field, the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune–immune interactions as well as immune–endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol, and human chorionic gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance, and termination of pregnancy. They suppress detrimental maternal alloresponses while promoting tolerance pathways. This includes the reduction of the antigen-presenting capacity of dendritic cells (DCs), monocytes, and macrophages as well as the blockage of natural killer cells, T and B cells. Pregnancy hormones also support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic DCs, and efficiently induce regulatory T (Treg) cells. Furthermore, they are involved in the recruitment of mast cells and Treg cells into the fetal–maternal interface contributing to a local accumulation of pregnancy-protective cells. These findings highlight the importance of endocrine factors for the tolerance induction during pregnancy and encourage further research in the field.
PMCID: PMC4021116  PMID: 24847324
progesterone; estradiol; human chorionic gonadotropin; luteinizing hormone; alpha-fetoprotein; immune regulation; pregnancy
7.  B Cells: The Old New Players in Reproductive Immunology 
Reproductive immunology research has long focused on T cell responses to paternal antigens and tolerance mechanisms supporting fetal well-being. The participation of B cells herein was not widely studied. Because of the fascinating immunological uniqueness of pregnancy, it is however to be expected that such pleiotropic cells play a considerable role. In fact, on the one hand B cells contribute toward pregnancy tolerance by secreting the immunomodulatory cytokine IL-10 but on the other hand can seriously harm pregnancy because of their capacity of producing autoantibodies. As for protective B cells, new evidences in mouse models arise suggesting that IL-10 producing B cells, the so-called B10 cells, help in maintaining tolerance toward semi-allogenic fetal antigens. They may be also important to fight danger signals at the fetal-maternal interface as, e.g., in the case of infections with the aim to restore the disrupted fetal tolerance. In human pregnancies, IL-10 producing B cells increase with pregnancy onset but not in the case of spontaneous abortions. In vitro, they are able to suppress TNF-α production by T cells from pregnant individuals. Their generation and functionality will be discussed throughout this review article. B cells can be deleterious to pregnancy as well. Aberrant B cell compartment is associated with obstetric pathologies. In particular, the capacity of B2 cells to produce specific autoantibodies or of B-1a B cells to secrete natural autoantibodies that can turn autoreactive will be discussed herein.
PMCID: PMC4066365  PMID: 25002862
pregnancy; B cells; autoantibodies; IL-10; Breg; B10 cells
8.  Male Breast Cancer: 20-Year Survival Data for Post-Mastectomy Radiotherapy 
Breast Care  2013;8(4):270-275.
The goal of this population-based study was to determine the impact of post-mastectomy radiation therapy on long-term overall survival (OS) of male patients with breast cancer.
Patients and Methods
We investigated 20-year OS rates of 664 patients diagnosed with primary stage I–III breast cancer in former East Germany between 1970 and 1989. Patients had a radical mastectomy with axillary lymph node dissection without systemic adjuvant therapy.
Median follow-up time was 26.2 years (range 19–38 years). 52.4% of the patients had post-mastectomy radiotherapy. Radiotherapy showed different effects in each stage group after 20 years. Whereas there was an OS trend for radiotherapy to harm patients with stage I disease (hazard ratio (HR) 1.45; 95% confidence interval (CI) 0.98–2.15; p = 0.065), radiotherapy showed no benefit in patients with stage II disease (HR 0.82; 95% CI 0.62–1.1; p = 0.15). There was a significant survival benefit for patients with stage III disease receiving radiotherapy (HR 0.60; 95% CI 0.41–0.88; p = 0.008).
Post-mastectomy radiotherapy is associated with longer OS in male patients with stage III breast cancer. Male breast cancer patients at stages I and II do not seem to benefit from radiotherapy, but obsolete irradiation techniques might explain adverse long-term effects in earlier stages.
PMCID: PMC3787884  PMID: 24132074
Male breast cancer; Adjuvant radiotherapy; Adjuvant Therapy; Overall survival
9.  Future Roles of Lapatinib in ErbB2-Positive Breast Cancer: Adjuvant and Neoadjuvant Trials 
Breast Care  2010;5(Suppl 1):22-24.
Lapatinib is potentially an ideal therapy for the adjuvant and neoadjuvant treatment of women with breast cancer due to its convenience of use (oral, once-daily administration) and because it has shown activity in the first-line and refractory metastatic settings. Furthermore, the dual tyrosine kinase inhibitor appears to have a low incidence of cardiotoxicity, and may decrease the rate of later brain metastases. Therefore, several cooperative groups and academic centers have initiated trials investigating lapatinib in the treatment of early-stage ErbB2 (HER2)-overexpressing breast cancer.
PMCID: PMC2931097  PMID: 20847929
Lapatinib; ErbB2-positive breast cancer; Adjuvant; Neoadjuvant; ALTTO study; TEACH study
10.  Zurich Consensus: German Expert Opinion on the St. Gallen Votes on 15 March 2009 (11th International Conference at St. Gallen: Primary Therapy of Early Breast Cancer) 
Breast Care  2009;4(2):109-116.
A German working group of 23 breast cancer experts discussed the results from the vote at this year's St. Gallen Consensus Conference on Primary Therapy for Early Breast Cancer (March 11–14, 2009) and came up with some concrete recommendations for day-to-day therapeutic decisions in Germany. Due the fact that the concept of the St. Gallen Consensus Conference merely allows for a minimal consensus, the objective of the working group was to provide practice-related recommendations for day-to-day clinical decisions in Germany. One area of emphasis at St. Gallen was tumor biology as a starting point for reaching individual therapeutic decisions. Intensive discussion was necessary with respect to the clinical relevance of predictive and prognostic factors. A new addition to the area of systemic therapy was a first-ever discussion of the adjuvant administration of bisphosponates and the fact that therapy with trastuzumab in HER2 overexpressing breast cancer has been defined as the standard for neoadjuvant therapy. The value of taxanes as a component of (neo)adjuvant chemotherapy as well as the value of aromatase inhibitors for the endocrine adjuvant treatment of postmenopausal patients were affirmed.
PMCID: PMC2931071  PMID: 21049070

Results 1-10 (10)