Search

Background: Estimating distant recurrence risk in women with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer is still challenging. EndoPredict ® is a gene expression-based test predicting the likelihood of recurrent disease. We analyzed the difference in oncological decision making with and without the knowledge of gene expression tests., Patients and Methods: This is a retrospective analysis including patients diagnosed with hormone-receptor positive, Her2 negative breast cancer between 2011 and 2015 at the Municipal Breast Cancer Centre Cologne, Germany. All patients received an evaluation by EndoPredict ® . An oncological tumor board (TB) with knowledge of these results served as a baseline (control group). This baseline was compared to the treatment decision (adjuvant chemotherapy yes vs. no) made by oncologists with different experience levels (less than 5 years, between 5 and 15 years, and more than 15 years) who were not provided the EndoPredict ® scores. All clinicians had access to clinical as well to histopathological data., Results: There was no significant difference between control group and the oncologists with different experience levels concerning a chemotherapy indication. A trend could be shown in the subgroup of nodal negative patients between the treatment recommendation and physicians with more than 15 years of experience (p = 0.088). A further trend could be demonstrated in the subgroup of patients with a low Ki67 index (≤ 14%) (p = 0.063) between physician with 5-10 years of clinical experience and official treatment recommendation., Conclusion: It seems that inexperienced physicians may profit from the use of EndoPredict ® to avoid an overtreatment. In nodal negative patients and patients with a low Ki67 index, undertreatment can be avoided with the use of EndoPredict ® (borderline significance). Further prospective studies with larger study cohorts are needed to further validate this tool.

Purpose: Primary and secondary sterility have become an issue of increasing importance due to demographic and social changes in society. Data regarding the association between female androgen levels and the probability of successful conception after fertility treatment are sparse and contradictive. This study was designed to assess this clinical question., Methods: In this retrospective single-center cohort study concentrations of androgens androstenedione, dehydroepiandrosteronsulfat (DHEAS) and testosterone (ng/ml) were investigated in the serum of patients presenting for sterility at the department of reproductive medicine of Saarland University hospital Homburg between January 2015 and December 2017. Androgen levels were correlated with reproductive outcomes. Statistical analysis was performed with the aid of SPSS version 24. Significance for conception rates in dependence of androgen concentration was assessed using Kruskal-Wallis test (significance was estimated with p < 0.05)., Results: The laboratory values of a total of 301 patients were examined (64% primary, 36% secondary sterility). Median age at first visit at the fertility department was 32.7 years (range 20-47 years). 64 pregnancies were observed during the study period (conception rate 21.3%). 23 out of 301 patients (7.6%) suffered from hypoandrogenaemia, 248 (82.4%) had normal androgen levels and 30 (10%) showed hyperandrogenaemia (p = 0.25). Regarding patients in whom fertility treatment was successful 3 (4.7%) showed hypoandrogenaemia, 54 (84.4%) were normoandrogenaemic and 7 (10.9%) had hyperandrogenaemia (p = 0.40 Kruskal-Wallis test)., Conclusions: We found no association between female androgen levels and sterility and reproductive outcomes.

Background: Retention of products of conception (RPOC) following delivery is rare. Clinicians often have the impression that a high proportion of patients with sonographically suspected RPOC following surgery have a negative histopathology. Hence, we aimed to report our single-center experience with suspected RPOC and histopathological outcome after surgery., Patients and Methods: In this retrospective analysis, patients who underwent surgery due to suspected postpartum RPOC were analyzed for potential predictive clinical and sonographic parameters., Results: A total of 32 patients with histopathologically-confirmed RPOC were compared with 21 patients with a negative histopathological report for RPOC. Endometrial hyperechogenic mass and clinical parameters such as pain, fever and bleedings were not predictive for RPOC. Increased age (p=0.001) and vaginal delivery (p=0.040) were significantly associated with RPOC., Conclusion: Clinical presentation alone is not predictive for RPOC. Vaginal delivery and younger age seem to be a risk factor and therefore have to be considered in patients with suspected RPOC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Immune infiltration is implicated in the development of acquired resistance to anti-angiogenic cancer therapy. We therefore investigated the correlation between neutrophil infiltration in metastasis of colorectal cancer (CRC) patients and survival after treatment with bevacizumab. Our study identifies CD177+ tumour neutrophil infiltration as an adverse prognostic factor for bevacizumab treatment. We further demonstrate that a novel anti-VEGF/anti-Ang2 compound (BI-880) can overcome resistance to VEGF inhibition in experimental tumour models., Methods: A total of 85 metastatic CRC patients were stratified into cohorts that had either received chemotherapy alone (n = 39) or combined with bevacizumab (n = 46). Tumour CD177+ neutrophil infiltration was correlated to clinical outcome. The impact of neutrophil infiltration on anti-VEGF or anti-VEGF/anti-Ang2 therapy was studied in both xenograft and syngeneic tumour models by immunohistochemistry., Results: The survival of bevacizumab-treated CRC patients in the presence of CD177+ infiltrates was significantly reduced compared to patients harbouring CD177- metastases. BI-880 treatment reduced the development of hypoxia associated with bevacizumab treatment and improved vascular normalisation in xenografts. Furthermore, neutrophil depletion or BI-880 treatment restored treatment sensitivity in a syngeneic tumour model of anti-VEGF resistance., Conclusions: Our findings implicate CD177 as a biomarker for bevacizumab and suggest VEGF/Ang2 inhibition as a strategy to overcome neutrophil associated resistance to anti-angiogenic treatment.

Background: Estimating distant recurrence risk in women with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer is still challenging. Oncotype DX® is a gene expression-based test predicting the likelihood of recurrent disease. This study analyzed the difference in oncological decision making with and without the knowledge of gene-expression tests based on oncological work experience., Materials and Methods: This was a retrospective analysis including n=113 patients diagnosed with hormone receptor-positive, HER2-negative breast cancer between 2011 and 2015 at the Municipal Breast Cancer Center Cologne, Germany. All 113 patients underwent evaluation by OncotypeDX®. An oncological Tumor Board with knowledge of these results served as baseline (control group). This baseline was compared to the treatment decision for adjuvant chemotherapy reached by oncologists with different experience levels (less than 5 years, between 5 and 15 years and more than 15 years) who were not provided the OncotypeDX® results., Results: Inexperience led to a significant increase in recommendations for chemotherapy, with those made by the Tumor Board being least frequent (41.6% vs. <5 years=55.6%, 5-15 years=50.4%, and >15 years=42.5%; p<0.05). An exploratory subgroup analysis showed the Tumor Board was significantly less likely to recommend chemotherapy for patients with Ki67 >14%, pN1 and postmenopausal status than were oncologists with up to 15 years experience, with a strong trend for those with tumor size larger than pT2., Conclusion: With a maximum reduction of 14.2% for those with the lowest level of oncological experience, the likelihood of recommending chemotherapy was found to decrease with increasing oncological work experience. A subgroup analysis showed that differences in decision making were most likely in patients with a Ki67 >14%, tumor sizes larger than pT2, pN1 and postmenopausal patients. It is the opinion of this study group that gene-expression testing is especially pertinent for these subgroups., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The role of ESR1 methylation in breast cancer and its influence on disease progression is not yet fully understood. Healthy breast tissue usually does not show ESR1 promoter methylation, whereas the frequency of ESR1 methylation appears to increase in primary breast cancer and in metastatic disease. Although women with ER positive breast cancer have a good prognosis, some will relapse. We aimed to evaluate the methylation status of ESR1 in primary breast cancer and its corresponding metastases by a methylation-specific real-time PCR and to correlate the methylation status with clinical outcome. Women who were treated for primary and metastatic breast cancer were included in the study. Tumor DNA was isolated from paraffin embedded tissue sections. After bisulfite treatment ESR1 promoter methylation was analyzed by real time-MSP of each tissue sample. Kaplan-Meier-Curves were drawn for survival. In the group of patients with positive ESR1 promoter methylation in the primary breast carcinoma survival was lower compared to the group of patients without methylation (38.1 months vs. 54.3 months, n.s.). Seven out of 19 (37%) of those patients with positive ESR1 promoter methylation developed loss of ER expression in metastatic disease. None of the patients who had primary tumours that were ESR1 methylation negative developed ER expression negative metastatic disease. The results underline the importance of the ESR1 promoter methylation and its potential application as a predictive marker. To improve the clinical outcome of patients with metastatic disease, those with initially positive ESR1 methylation status should undergo a tissue biopsy already at the beginning of metastatic disease to identify those with loss of ER expression and thus resitance to anti-endocrine therapy.

Background: Breast cancer is a heterogenous and complex disease. A rare site of metastatic breast cancer disease is the neck. Data about supraclavicular metastases in patients with metastatic breast cancer are still lacking. Hence, our study aimed to analyze histological subtypes of supraclavicular metastases compared to the primary site., Materials and Methods: This was a retrospective hospital-based cohort study of patients with breast cancer who developed supraclavicular metastases. Diagnosis of supraclavicular metastases was confirmed by biopsy or diagnostic lymph node extirpation. Histological subtypes were analyzed and Kaplan-Meier estimates were calculated for overall survival., Results: A total of 20 patients were included in the analysis. The majority of the patients (12/20) had hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative supraclavicular metastases, disease in 3/20 patients was HR-positive/HER2-positive, HR-negative/HER2-positive in 1/20 patients and basal-like in 4/20 patients. Total discordance rates for estrogen receptor, progesterone receptor and HER2 between primary and metastatic tumors were 20.0%, 36.8% and 29.4%, respectively. The 5-year overall survival was 80%, whereas the 5-year survival after the onset of neck metastasis was 45%., Conclusion: As a rare site of metastatic breast cancer, supraclavicular metastases are associated with a worse median overall survival from their onset. The high rate of discordance of histological subtype stresses the necessity for biopsies in patients with supraclavicular metastasis., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To evaluate instrumental usage in laparoscopic gynecological surgeries and to develop key timesets of a laparoscopic operation, which allows categorization of the operation time into different sections., Methods: In this prospective clinical observational study, frequency of instrument usage, time for instrument switches, and instrument utilization time were recorded in a standardized manner for laparoscopic surgeries in 103 endoscopic surgeries., Results: A standard equipment (including atraumatic grasping forceps, irrigation and suction device, bipolar clamp, and laparoscopic scissors) was used for nearly all interventions. Bipolar clamps and scissors were changed most frequently. The tool used for the longest amount of time was the atraumatic grasping forceps. Laparoscopic instruments were switched 51 times per surgery (range 2-250 times). One instrument switch lasted for a median of 0.13 min (0.08-1.2 min). Median time for instrument switch for a single surgery added up to 6.83 min. Instrument switches required 10.5% of the overall operation time., Conclusion: We analyzed the current instrument usage in laparoscopic gynecological surgeries. The results of our standardized investigation suggest ways to reduce the time required for surgery and provide starting points for the standardization of the work routine.

Introduction Cervical cancer is the fourth most frequent cancer in women worldwide. Addition of the VEGF antibody bevacizumab in combination with platinum-containing chemotherapy achieved an improvement in overall survival in advanced cervical cancer. To date there are no data on neoadjuvant use of bevacizumab. We therefore studied the benefit of neoadjuvant combined therapy with bevacizumab in a group of cervical cancer patients. Patients and Methods This retrospective cohort study analysed 14 patients with cervical cancer FIGO stages 1b1 to IV who received neoadjuvant platinum-containing chemotherapy in combination with bevacizumab. The comparative cohort consisted of 16 patients who were treated with neoadjuvant platinum-containing chemotherapy alone. The response rates were determined by means of preoperative clinical examination, diagnostic imaging (RECIST), changes in tumour markers (SCC) and by histopathology. Results A clinical response was found in 93.8% (n = 15) of patients after bevacizumab-free therapy and in 100% (n = 14) of the patients who were treated with bevacizumab in addition. Combined therapy with bevacizumab led to a higher rate of clinical complete remission (42.9 vs. 12.5%; p = 0.072) and significantly improved the reduction in tumour size (Δ longest diameter: 3.7 vs. 2.5 cm; p = 0.025). Downgrading was observed in 100% of all patients treated with bevacizumab compared with 75% in the control arm. The rate of pathological complete remission (pCR) was not altered significantly (28.6% [n = 4] vs. 37.5% [n = 6]; p = 0.460). Discussion Overall, combined therapy with bevacizumab led to a better clinical response. Operability was therefore improved more often. Because of the small patient cohort, larger prospective studies are necessary to validate the effect of neoadjuvant combined therapy with bevacizumab.

Purpose: Gynecologists working in emergency department services in hospitals lately have the impression that the number of pregnant women who present themselves because of anxiety or uncertainty is increasing. Hence, the aim of this study was to assess reasons of pregnant women for presenting themselves to an emergency department. Of special interest was how far a diagnosis could be confirmed for the symptoms pregnant women complained about., Methods: This is a prospective questionnaire-based study conducted between April 2015 and April 2016 in the Department of Gynecology and Obstetrics of the University Hospital of Cologne. The questionnaire was placed in the waiting area of the emergency department service for pregnant women. Pregnant patients were included with a gestational age of above 20 weeks of gestation., Results: 331 patients were enrolled in this study. The most frequent reason for emergency department use was "pain" in 28.3% and cervical insufficiency in 19.7% of all cases. 45.6% (n = 151) of the patients had a recommendation of an outpatient practice for presentation to emergency department service. 36.3% (n = 120) of all patients were admitted to hospital for further treatment, 58.6% (n = 194) could be released from hospital. 3.3% (n = 11) of all patients rejected recommended further treatment in hospital. A trend was demonstrated concerning former abortion and hospital admission (p = 0.062)., Conclusions: The high amount of patients making nonurgent use of emergency department services indicates potential uncertainty in interpretation of symptoms. Patients with former abortion history were admitted more often to hospital, and therefore need special attention during pregnancy.

Background/aim: The Ki-67 index is chiefly important for distinguishing between luminal A and luminal B human epidermal growth factor receptor 2 (HER2neu)-negative breast cancer subtypes. However, its ability to predict response to chemotherapy is uncertain., Patients and Methods: Patients treated for primary breast cancer at the University Hospital of Cologne were identified. Immunohistochemistry for Ki-67 detection was performed according to standard protocols. Kaplan-Meier survival curves were calculated and compared using the log-rank test., Results: Patients with low Ki-67 index had a significantly better disease-free-survival (DFS) than patients with high Ki-67 index (hazard ratio=2.85; 95% confidence interval=1.45-5.59; p=0.002). A significant influence on DFS was demonstrated (hazard ratio(HR)=1.02; confidence interval(CI)=1.00-1.04; p=0.048) within the subgroup of hormone receptor-positive and HER2neu-negative patients, but not within the subgroup of those with luminal B/HER2neu-negative tumors (DFS: p=0.801; overall-survival: p=0.379)., Conclusion: The Ki-67 index has a prognostic impact on DFS in patients with hormone receptor-positive and HER2neu-negative tumors. The strict cut-off value was not suitable for distinguishing between high- and low-risk patients and their response to adjuvant chemotherapy., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Chemotherapy with anthracyclines is associated with life-threatening electrocardiographic alterations including corrected QT (QTc) interval prolongation., Patients and Methods: In this study we assessed the effect of epirubicin, cyclophosphamide, and docetaxel (EC-Doc) on the QTc interval in 10 patients with early breast cancer. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography (ECG), and serum cardiac markers at baseline and after 4 cycles of EC and 4 cycles of docetaxel. To evaluate the influence of interobserver variation, the QTc interval was analyzed by a cardiologist, a gynecologist, and with automated ECG interpretation software., Results: There was a significant QTc prolongation after EC treatment independent of the investigator. In addition, a significant increase in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels was noted after EC treatment. QTc prolongation and NT-proBNP levels normalized after docetaxel treatment. Other biochemical markers were within normal ranges. No clinically relevant effect on left ventricular ejection fraction was observed., Conclusion: This prospective study demonstrated that EC treatment increases the QTc interval and NT-proBNP levels in women with early breast cancer. This effect was reversible and independent of docetaxel administration. Moreover, the treating physician can safely perform QTc interval evaluation as part of clinical routine independent of his/her specialty. Due to the small number of patients, further conclusions are limited at this point.

Objectives: Since the introduction of the sentinel node technique for breast cancer in the 1990s patient's morbidity was reduced. Tracer uptake is known to be dependent from lymph node integrity and activity of macrophages. The aim of this study was to assess whether radioactivity of the tracer can predict sentinel lymph node metastases. Furthermore, a potential association with Ki-67 index was examined. Non-invasive prediction of lymph node metastases could lead to a further decrease of morbidity., Methods: We retrospectively analyzed patients with primary breast cancer who underwent surgery at the Department of Obstetrics and Gynecology in the University Hospital of Cologne between 2012 and 2013. Injection of radioactive tracer was done a day before surgery in the department of Nuclear Medicine. Clinical data and radioactivity of the sentinel node measured the day before and intraoperatively were abstracted from patient's files., Results: Of 246 patients, 64 patients had at least one, five patients had two and one patient had three positive sentinel lymph nodes. Occurrence of sentinel lymph node metastases was not associated with preoperative tracer activity (p = 0,319), intraoperative tracer activity of first sentinel node (p = 0,086) or with loss of tracer activity until operation (p = 0,909). There was no correlation between preoperative Ki-67 index and occurrence of lymph node metastases (p = 0,403)., Conclusion: In our cohort, there was no correlation between radioactivity and sentinel node metastases. Tracer uptake might not only be influenced by lymph node metastases and does not predict metastatic lymph node involvement., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Inguinal lymph node (LN) metastasis is a crucial prognostic factor in vulva carcinoma. The aim of this study was to determine the prognostic value of the number of resected LNs in patients with vulvar carcinoma on recurrence rates., Methods: This retrospective study includes patients with vulvar squamous cell carcinoma who underwent inguinofemoral lymphadenectomy (IFL) between 1998 and 2011. Dissected groins were stratified by the number of removed lymph nodes (<6 LNs versus ≥6 LNs) or inguinal LN metastasis (pN- versus pN+) and analyzed according to groin, local and distance recurrence rates., Results: In total 45 patients were identified and 79 groins were eligible for this analysis. 11 patients underwent ipsilateral IFL and 34 bilateral IFL. The median age was 58 years (range 31-80). The median tumor size was 2 cm (range 0.1-7.9). A median of 8 (range 0-19) LNs were resected per groin. Overall in 11 groins LN metastases were found. Groin recurrences occurred in four patients, local recurrence in six patients and distant metastasis in one patient. We did not observe any significant improvement in groin recurrence rates, local recurrence rates and distant recurrence rates if more than six LNs were removed per groin. Notably, patients with LN metastasis did not show higher recurrence rates compared to unaffected LNs., Conclusion: In this cohort we demonstrated that resection of more than six LNs per groin does not improve the recurrence rates in patients with carcinoma of the vulva. Further prospective studies with more individuals are needed to evaluate the role of resected LNs in vulvar carcinoma.

Purpose: Invasive cervical cancer is today the fourth most common cancer of women in western civilization. Screening programs have led to a continuously decrease. Nevertheless, both screening and a positive test result are known to be associated with a negative psychological impact. Screening programs in European countries differ and thus psychological impact might as well. The aim of this study was to evaluate the psychological impact of women with an abnormal Pap smear in a German cohort., Methods: Between July 2013 and May 2014, a self-assessment questionnaire was distributed to 595 patients that were referred to a special clinic for cervical dysplasia for further evaluation of an abnormal Pap smear. Patients were recruited in five different centers., Results: Most patients (45.9 %) were informed about the test result via phone call by their doctor. 68.8 % of the patients felt anxious and 26.3 % even felt panic. After having talked to their physician, 51.4 % of our cohort still felt worried and only 24.4 % felt reassured. Concerning disease management, 48.4 % underwent a control Pap smear in 6 months. The preferred information source was the physician (63.9 %). Compared to the results in other European countries, our study cohort showed differences concerning age distribution, patients living in a partnership, number of children and especially disease management., Conclusion: Cancer screening itself and abnormal test results have an impact on patient's feelings. To reduce the psychological impact, patients need to be better informed about the risks and benefits of cancer screening programs and in case of cervical cancer screening about the meaning of an abnormal test result. Our results underline the importance of a trustful physician-patient relationship in that matter.

Background/aim: Estrogen receptor-alpha is usually expressed in normal cervical tissue, but its presence is decreased or absent in invasive cervical cancer indicating that its expression is lost during development of invasive cervical cancer. The aim of the present study was to investigate ESR1 promoter methylation in cervical cancer and correlate methylation status with clinico-pathological parameters., Materials and Methods: Fifty patients treated for cervical cancer were included in the study. Isolation and bisulfite treatment of genomic DNA from cervical cancer tissue was performed by commercially-available kits. Methylated ESR1 promoter sequences were detected by quantitative real-time methylation-specific PCR., Results: Methylation status did not present differences regarding age at-diagnosis, FIGO stage, grade, BMI and overall survival for all patients, but within the subgroup of non-keratinizing squamous cell cancer methylation status correlated with grading (p=0.047)., Conclusion: Methylation of the ESR1 promoter does not seem to be of any prognostic relevance, but is associated with higher tumor grading of cervical cancer patients.