Search

Introduction: The pelvic floor is exposed to differing stresses and trauma depending on the mode of birth. At the same time, the pelvic floor plays a crucial role in female sexual functioning (FSF). Whereby FSF encompasses different dimensions, from subjective satisfaction to physiological aspects, such as lack of pain and orgasm ability. The aim of the study presented here is to assess FSF in relationship to postpartum pelvic floor disorder based on the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR), in a large convenience sample and to identify whether there is an association between mode of birth as well as perineal injuries and FSF of women up to 24 months postpartum., Material and Methods: We conducted a cross-sectional online survey and recruited via social media women up to 24 months after birth of their last child. FSF was surveyed using the PISQ-IR. Details were also collected on all previous births and birth-related perineal trauma, as well as current breastfeeding, obesity, and socio-demographics. Multivariate models were then calculated to determine a possible association between FSF and birth mode., Results: The data basis is the responses of 2106 survey participants within the first 24 months postpartum. Even 12-24 months postpartum, 21% of respondents are not sexually active, which burdens almost 44% of these women. With regard to mode of delivery, differences in FSF are only evident in individual dimensions of the PISQ-IR. The dimensions "Condition Impact" and "Condition Specific" were significantly associated with more impairments in sexually active respondents up to 12 months postpartum whose last mode of delivery was forceps or vacuum extraction. If a perineal tear had occurred during last birth, this was significantly associated with a lower PISQ-IR subscore in the "Condition Impact," "Condition-Specific," "Global Quality," "Partner-Related," and "Arousal" models. The low variance explanation shows that further relevant factors on female sexuality may exist., Conclusions: The issue of impairments in FSF following childbirth, persisting for an extended period of time, is a significant postpartum concern. Due to the very different dimensions of FSF, the influence of the mode of delivery must be considered in a differentiated way., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background/aim: The trend in today's surgical gynecological oncology is to provide equal oncological safety with less radical surgery. The SHAPE trial demonstrated the non-inferiority of a simple hysterectomy compared to a radical hysterectomy in low-risk cervical cancer. As a result, the accuracy of preoperative diagnostics has become increasingly important to avoid both under- and overtreatment. The aim of the study was to investigate the accuracy of MRI-based T-stage., Patients and Methods: Forty-five patients who were surgically treated for an initial diagnosis of a primary cervical carcinoma at the University Hospital Cologne in the Department of Gynecology and Obstetrics between 2015 and 2021 were included in the study. All patients underwent MRI prior to their surgical treatment., Results: In 44.4% of cases, the pathological tumor size in the surgical specimen was consistent with the preoperative tumor size determined by MRI. In 28.9% of the cases, MRI overestimated the final pathologic T-stage while in 26.7% of cases, MRI underestimated it. Furthermore, we were able to show that overall survival was significantly poorer (p<0.05) in patients whose preoperative MRI had underestimated the final T-stage in our study cohort., Conclusion: Preoperative MRI diagnostics alone are not reliable enough for accurate T-stage estimation. Multimodal diagnostic approaches are essential for accurate preoperative staging. Prospective trials are needed to evaluate preoperative staging strategies to optimize sizing accuracy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study investigated the clinical impact of resection of pelvic sentinel lymph nodes (PSLNs) in squamous cell vulvar cancer (SCVC)., Patients and Methods: Sixty-two groins of 33 patients with SCVC who underwent sentinel lymph node (SLN) resection between 2010 and 2021 at the University Hospital of Cologne, Germany, were analyzed in this retrospective cohort study. The frequency of additionally resectable PSLNs, histological findings, and count rates were analyzed and compared to the findings for inguinal sentinel lymph nodes (ISLNs)., Results: In all patients and in 61 (98%) of the 62 radiolabeled groins, at least one SLN could be resected. Five (8%) of the 62 groins had histologically confirmed lymph node metastases (4/33 patients, 12%). Twenty (33%) of the 62 groins underwent additional PSLN resection. Resection of these PSLNs was feasible without causing an additional burden for the patients. None of the PSLNs showed signs of tumor infiltration. Information on the extent of radioactivity for ISLNs and simultaneously for PSLNs, expressed as count rate of intraoperative measurement with the gamma probe, was available for 20 (32%) groins. In three (15%) of these cases, the highest count rate in a SLN was found in a PSLN and not in an ISLN., Conclusion: Resection of PSLNs is feasible and can be performed without short-term complications. In patients with early SCVC, resection of PSLNs is not necessary, even in those with early infiltration of inguinal lymph nodes. The intraoperative count rate of SLN is not relevant for the decision to perform resection., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Anatomical and functional aspects of the lymphatic drainage of the uterine corpus in endometrial cancer are demonstrated. Main lymphatic pathway runs along the upper pelvic pathway from the uterine artery first line to the medial external iliac nodes, followed by the lateral external and common iliac node basin. The second important pathway runs along the ovarian vessels directly to the paraaortic nodes. Pathways may visualized best by injection of indocyanine green (ICG) into the uterus. In contrast to the upper pelvic pathway visualized by cervical injection, the paraaortic drainage can only be marked by corporal injection. Lymphatic drainage works downstream (peripheral to central, with respect to vascular valves) only. Clinically, pelvic sentinel node excision replaced systematic lymphadenectomy for diagnostic purposes and even paraaortic node staging can be omitted in most of pelvic node negative patients. For therapeutic purposes compartmental resection of the uterus together with its lymphovascular system and first line nodes "en bloc" could be an option as performed in peritoneal mesometrial resection/targeted compartmental lymphadenctomy (PMMR/TCL)., Competing Interests: Declaration of competing interest Rainer Kimmig declares potential conflicts of interest: presentations, advisory boards, proctorings, travel fees for Intuitive Surgical, Medtronic, Medicaroid, Cambridge Medical Robotics, Avatera, Cava Robotics and Active Surgical. Fabinshi Thangarajah and Paul Buderath declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Pelvic floor disorders (PFD) occur in about 40% of women after delivery. Less is known about the intervention and care needs of women with postpartum PFD. The aim of this analysis was to analyze care needs and self-initiated measures to strengthen the pelvic floor in postpartum women in relation to incontinence and sexual dysfunction. Furthermore, influencing factors for self-initiated measures were evaluated., Patients and Methods: An anonymous online survey (via LimeSurvey) was conducted between September and October 2022 and distributed via social media (Instagram and Facebook). The survey explicitly addressed mothers with and without pelvic floor disorders up to 5 years postpartum (inclusion criteria). Validated instruments were employed to assess incontinence (ICIQ-SF) and sexual functioning (PISQ-IR: Condition Impact). The questions on the use of services and preventive measures, as well as on the interaction with a gynecologist, were based on self-developed items., Results: In total, 49.4% of the participants of the survey showed symptoms of urinary incontinence (UI). Furthermore, only 40.3% (n = 241) of women were actively asked by their gynecologists for the occurrence of UI or PFD among those who suffered from PFD. Overall, 79.3% of the participants of the survey with UI underwent measures to deal with the complaints. The ICIQ-SF Score was significantly associated with all self-induced measures. High School diplomas and academic degrees were associated with the use of love balls (p < 0.05)., Conclusion: The results of the study show the unmet needs of postpartum women. PFD should be addressed more frequently in the outpatient setting. Furthermore, more systematic information about the treatment of PFD could help to address unmet information needs and improve interventions., (© 2024. The Author(s).)

Background/aim: To date, magnetic resonance imaging (MRI) remains the gold standard for diagnosing breast implant rupture. As MRI is an expensive procedure with limited availability, the improvement of sonographic assessment is desirable. A potentially useful tool in this regard is elastography. To evaluate the diagnostic benefits of strain elastography and shear wave elastography under standardized conditions we developed an animal model., Materials and Methods: An animal model was created by preparing an implant site in a chicken breast, imitating tissue layers covering a breast implant after mastectomy. Different broken and intact implants were inserted. Thereby, measurements were performed using strain elastography and shear wave elastography. For strain elastography, the resulting images were investigated on repeated patterns. The data generated by shear wave elastography were analyzed for significant differences between the ruptured and intact implants., Results: The animal model using chicken breast generated realistic images and measurements comparable to those of a human breast. Hence, ruptured and intact implants could be compared under standardized conditions. Statistical analysis showed no significant difference between intact and ruptured implants with respect to the data generated by shear wave elastography. Qualitative analysis using strain wave elastography showed different patterns between intact and ruptured implants in the animal model. Intact implants showed a characteristic sonographic image of three layers in certain levels., Conclusion: Shear wave elastography does not seem to produce reliable data for the evaluation of breast implants, whereas qualitative analysis using strain elastography might be a useful tool to improve diagnostic accuracy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Staging for breast cancer in advanced stages or prior to neoadjuvant chemotherapy is recommended to be performed with CT scan of the chest and abdomen and a bone scan. This recommendation is valid since 2012, when conventional staging with chest x-ray and ultrasound of the abdomen was replaced by the more sensitive CT scan. However, it remains unclear if this approach improves patient outcome and prognosis., Patients and Methods: We identified patients who were treated for breast cancer at the breast center of the St. Elisabeth Hospital, Cologne, in 2012 and 2014. Clinical information such as age at diagnosis, stage, tumor biology, grading, and the applied method for staging was abstracted from the patient chart. We also looked for local or distant recurrence and data of survival., Results: A total of 1,122 patients were identified. Of those, 104 patients developed local or distant recurrence and 54 died. Conventional staging with chest x-ray, abdominal ultrasound and a bone scan was more often in 2012 (482 cases) than in 2014 (135), but CT-staging was more often in 2014 (180 vs. 29 cases). In general, less patients were staged in 2014 than in 2012. There were no significant survival differences between the two groups., Conclusion: Staging habits changed in 2012 compared to 2014 according to the changes in guidelines. This change did not affect disease-free survival., Competing Interests: The Authors have no conflicts of interest to declare in relation to this study., (Copyright 2023, International Institute of Anticancer Research.)

Purpose: More than 99% of cervical cancers and up to 40% of vulvar cancers are human papillomavirus (HPV) related. HPV 16 and 18 are the most relevant subtypes. Novel technologies allow the detection of minimal amounts of circulating cell-free HPV DNA (ccfHPV-DNA). The aim of this study was to evaluate ccfHPV-DNA assessed by droplet digital PCR (ddPCR) as a biomarker for molecular therapy monitoring in early, advanced, relapsed and metastatic HPV-driven cervical and vulvar cancer., Methods: Inclusion criteria of the study were histologically proven HPV 16/18-driven cervical and vulvar cancer with first diagnosed disease, newly diagnosed recurrence, or progression of disease. Blood samples were taken pre- and post-therapeutically. Circulating cell-free HPV DNA was quantified using ddPCR and the results were correlated with clinical data., Results: The mean copy number of ccfHPV-DNA was 838.6 (± 3089.1) in pretreatment and 2.3 (± 6.4) in post-treatment samples (p < 0.05). The copy number of ccfHPV-DNA increased with higher FIGO stages (p < 0.05), which are commonly used for clinical staging/assessment. Furthermore, we compared the distribution of copy numbers between T-stage 1 versus T-stage 2/3. We could show higher copy number level of ccfHPV-DNA in T-stage 2/3 (p < 0.05)., Conclusions: Therapy monitoring with determination of ccfHPV-DNA by ddPCR with a small amount of plasma reflects response to therapy and appears feasible for patients in advanced cancer stages of cervical and vulvar cancer. This promising tool should be examined as marker of therapy monitoring in particular in novel HPV-directed therapies., (© 2023. The Author(s).)

Purpose: Platelet-rich plasma (PRP) is widely used product, and meta-analyses showed this product to be beneficial when applied to a wound area. This study group has already demonstrated increased patient satisfaction and lower complication rates in breast cancer patients who received PRP after removal of their subcutaneous venous access device. This work is a follow-up analysis focusing on oncologic safety. Currently, there is no long-term data on the use of PRP products in cancer patients available yet., Methods: Between the years 2012-2016, venous access device removal was supported with the application of Arthrex ACP ® (Autologous Conditioned Plasma)-a PRP product to improve the wound-healing process. All surgeries were performed in the breast cancer center of the municipal hospital of Cologne, Holweide, Germany. 35 patients received an application of Arthrex ACP ® after port removal compared to the control group of 54 patients. Endpoints were local recurrence-free, distant recurrence-free as well as overall survival., Results: Median follow-up was 45 months. No (0) adverse events were shown for cancer recurrence within the subcutaneous venous access device scar area. Thus, there seems to be no local oncogenic potential of the PRP product. All other endpoints as well as any-cause death numerically favor PRP use., Conclusion: PRP products such as Arthrex ACP ® seem to be oncological inert when applied after removal of subcutaneous access devices. This is the first study providing long-term data about overall survival, distant recurrence-free and local recurrence-free survival after applying PRP in high-risk cancer patients., (© 2022. The Author(s).)

Background/aim: Magnetic resonance imaging (MRI) is an important diagnostic tool in the detection of breast cancer. The Breast Center of the municipal Hospital Holweide, Cologne, annually cares for and treats patients with changes in the breast. A special problem is posed by Breast Imaging-Reporting and Data System (BI-RADS) 4 lesions. If a BI-RADS 4 finding is present, is a vacuum biopsy indicated in every case or, if there is already an indication for surgery due to other findings, can the corresponding finding be removed openly without histological clarification? We require real world data regarding the actual in-center likelihood of a BIRADS 4 lesion to be DCIS (Ductal carcinoma in situ) or invasive disease., Patients and Methods: This is a retrospective study of 1,641 patients who received MRI examination in the radiological department of the municipal hospital Holweide in 2012 and 2013. Each BI-RADS 4 finding (or higher) classified by MRI was compared with the final histological result., Results: 347 MRIs showed BI-RADS 4 findings or higher and 280 (80.7%) cases showed benign histology. In 67 (19.3%) cases, histology showed DCIS or invasive carcinoma., Conclusion: BI-RADS 4 lesions have a low probability of malignancy based on real-world data from this center. If there is already an indication for surgery due to other lesions, the patient can also be offered a simultaneous open biopsy in the context of the already initiated surgical treatment. Each center should know the sensitivity and specificity of the MRI imaging performed and counsel patients based on that., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Labor is induced in 1 out of 5 pregnancies. This is why we aimed to compare two different protocols of orally administered misoprostol for the induction of labor (IOL), with special regard to maternal and fetal outcome, delivery mode and duration., Patients and Methods: One hundred and twenty four patients with a medical indication for IOL were divided into two groups: Group A (n=63), which initially received 50 μg misoprostol escalated to 100 and, subsequently, to 200 μg every 4 h with a daily maximum of 600μg, between 11/2007 and 01/2008; and Group B (n=61), which initially received 25 μg misoprostol followed by 100 μg every 4 h with a daily maximum of 300 μg, between 12/2009 and 04/2010., Results: The mean administration-delivery interval was significantly lower in Group A (19.0 h) compared to Group B (27.1 h, p<0.05). Overall caesarean section rate, average birth weight, APGAR score, umbilical cord pH and meconium-stained fluid rates were similar between both groups., Conclusion: A higher dosage protocol of orally administered misoprostol significantly reduces the mean induction-delivery interval without increasing the risk for an adverse maternal or fetal outcome., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pyomyoma of the uterus is a rare but severe complication of uterine artery embolization (UAE). This report describes the uterus-preserving management of a case of fast-developing pyomyoma. Screening methods to minimize the risk of this condition are discussed., Case: A 46-year-old woman presented with fever, abdominal pain and blood stream infection on the third day after UAE, which had been performed to treat symptomatic uterine myomatosus. Broad-spectrum antibiotics proved inadequate. Magnetic resonance imaging (MRI) showed a possible superinfection of the necrotic myoma. Vaginal smear showed the same organism, a resistant Escherichia coli , as in the blood culture. Because the patient declined hysterectomy, multiple hysteroscopies with removal of necrotic pyomyoma were performed. In addition, an intrauterine gentamicin chain was placed. To our knowledge, this is the first case of pyomyoma immediately after UAE and the first report of successful hysteroscopic treatment in a septic patient., Conclusion: In order to reduce the risk of pyomyoma, pre- and postinterventional algorithms should be used., (© 2022 The Authors.)

Aim:  Probability of survival of patients with vulvar cancer directly depends on the lymph node status. Surgery of lymph nodes can be performed as radical inguinofemoral lymphadenectomy or in cases with certain conditions as sentinel lymph node surgery. The aim of this study is to obtain an overview of the intervention-related morbidity and quality of life in patients with vulvar carcinoma after lymphadenectomy., Methods:  Quality of life and morbidity was compared between patients who underwent radical inguinofemoral lymphadenectomy with those who underwent sentinel lymph node surgery., Results:  All recorded postoperative complications occur more frequently in the non-sentinel group, Significant difference was shown for the occurrence of lymphedema (p-value = 0.024) and sensitivity loss (p-value = 0.024). Recurrence of disease was more frequent in the non-sentinel group (38 % vs. 20 %, p = 0.621, n.s.) and satisfaction with groin surgery is slightly higher in the sentinel group (94 % vs. 89 %, p = 1.000, n.s.)., Conclusion:  We could demonstrate a significantly lower morbidity of sentinel lymphadenectomy compared to conventional inguinofemoral lymphadenectomy while maintaining the same oncological safety. The low morbidity of sentinel- lymphadenectomy does not seem to influence the postoperative quality of life significantly. However, recording of the individual burden of lymphadenectomy by questionnaires should be optimized., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The role of B cells in antitumor immunity and their impact on emerging immunotherapies is increasingly gaining attention. B-cell effector functions include not only secretion of antibodies, but also presentation of antigens to T cells. A physiologic B-cell subset with immunostimulatory properties was described in humans, defined by a high expression of CD86 and downregulation of CD21. We used multicolor flow cytometry and IHC to elucidate abundance and spatial distribution of these antigen-presenting B cells (BAPC) in blood (peripheral blood mononuclear cells, PBMC) and tumor samples of 237 patients with cancer. Antigen-specific T-cell responses to cancer testis antigens were determined using tetramer staining and sorted BAPCs in FluoroSpot assays for selected patients. We found that BAPCs were increased in the tumor microenvironment of 9 of 10 analyzed cancer types with site-specific variation. BAPCs were not increased in renal cell carcinoma, whereas we found a systemic increase with elevated fractions in tumor-infiltrating lymphocytes (TIL) and PBMCs of patients with colorectal cancer and gastroesophageal adenocarcinoma. BAPCs were localized in lymphoid follicles of tertiary lymphoid structures (TLS) and were enriched in tumors with increased numbers of TLSs. BAPCs isolated from tumor-draining lymph nodes of patients with cancer showed increased percentages of tumor antigen-specific B cells and induced responses of autologous T cells in vitro . Our results highlight the relevance of BAPCs as professional antigen-presenting cells in tumor immunity and provide a mechanistic rationale for the observed correlation of B-cell abundance and response to immune checkpoint inhibition., (©2021 American Association for Cancer Research.)

The immune response against cancer is orchestrated by various parameters and site-dependent specificities have been poorly investigated. In our analyses of ten different cancer types, we describe elevated infiltration by regulatory T cells as the most common feature, while other lymphocyte subsets and also expression of immune-regulatory molecules on tumor-infiltrating lymphocytes showed site-specific variation. Multiparametric analyses of these data identified similarities of renal and liver or lung with head and neck cancer. Co-expression of immune-inhibitory ligands on tumor cells was most frequent in colorectal, lung and ovarian cancer. Genes related to antigen presentation were frequently dysregulated in liver and lung cancer. Expression of co-inhibitory molecules on tumor-infiltrating T cells accumulated in advanced stages while T-cell abundance was related to enhanced expression of genes related to antigen presentation. Our results promote evaluation of cancer-specific or even personalized immunotherapeutic combinations to overcome primary or secondary resistance as major limitation of immune-checkpoint inhibition.

Subcutaneous nipple sparing mastectomies (NSM) are an important tool in modern oncoplastic surgery. Especially when an immediate implant-based reconstruction (IBR) is desired, clean margins are of the utmost importance. Central nipple biopsies during surgery serve two main purposes. Most importantly, it is hypothesized that intraoperative pathological evaluation of this biopsy may increase clean margin resection rates. In addition, a general recurrence risk reduction may occur due to the elimination of glandular and ductal components within the nipple. This analysis is a single center, multi-surgeon, retrospective, head to head analysis. Starting in March 2015, intraoperative central nipple biopsy in NSMs with IBR was introduced at the Municipal Breast Cancer Centre Cologne, Holweide, Germany. This trial retrospectively evaluates global complication rates, clean margin status and local recurrence rates for cohort 1 (NSM/no nipple biopsy, n = 103) vs. cohort 2 (NSM with nipple biopsy, n = 108) Median follow-up was 15 months. All implant-based reconstruction procedures used an epipectoral implant pocket. Cohorts were comparable. Global complication rates slightly favored the nipple biopsy cohort with respects to implant loss rate. An involved central nipple biopsy was found in 4.6% (n = 5/108) of the performed NSM procedures leading to the immediate removal of the nipple areola complex. All positive retro-areolar biopsies correlated with a positive nipple biopsy. However, in n = 1 case we found DCIS discontinual proliferation with an involved nipple biopsy, without a correlating positive retro-areolar biopsy (ie, 1 false-negative case was prevented). For the 15 month follow-up, there was no case of local recurrence within nipple areola complex for both cohorts. With this retrospective head to head analysis of 211 patients, it was shown that the central nipple biopsy correlates well with the retro-areolar biopsy. There may be a reduction in false negative rates. The procedure is safe to use and should be offered to NSM patients., (© 2021 The Authors. The Breast Journal published by Wiley Periodicals LLC.)

Background/aim: Postoperative infection in implant-based reconstructive breast surgery is a common problem. The preoperative application of a disinfecting washing agent may reduce postoperative infection rates. This retrospective analysis aimed to evaluate whether preoperative Octenisan ® application yields a reduction in postoperative complications or infection rates in breast reconstructive surgery., Patients and Methods: Between 2016 and 2019, 127 women received implant-based breast reconstruction at the municipal hospital of Cologne, Holweide, Germany. A total of 197 treatments were performed. After giving consent, patients were asked to use Octenisan ® wash lotion for five days before breast reconstructive surgery. All patients were asked by a simple questionnaire whether they performed showering and washing according to the proposed protocol. In 96 cases patients did adhere to the protocol. In 101 cases they did not. Patient cohorts were then divided into patients who had applied Octenisan ® wash lotion and patients who had not. Endpoints were defined as minor complications with no implant loss and major complications with consecutive implant loss., Results: Patient adherence to the application regimen was 48.7%. Overall minor complications occurred in 34.4% with preoperative Octenidine usage and 36.6% without preoperative Octenidine usage. Major complications happened in 7% with preoperative Octenidine and 5% without Octenidine. Overall, there was no significant difference concerning minor or major complication rates., Conclusion: Preoperative washing protocols involving the Octenisan ® wash lotion is relatively cheap and easy to follow. There is evidence that washing protocols result in a reduction of S. aureus infections leading to a better perioperative outcome. Octenisan ® is safe to use in implant-based breast reconstructive surgery and is not associated with higher risks for patients. Our study did not yield any significant reduction in perioperative and postoperative complication and infection rates. This is attributed to a relatively low study population. Wash lotion compliance was only 48.7%. Proper patient education is crucial. With those preliminary data, it is now possible to design a larger analysis since patient adherence to washing protocol with Octenisan ® wash lotion has been established., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: In Germany, performance of an emergency Cesarean section (ECS) is recommended within an interval of ≤20 min from decision to delivery (DDI). The aim of the study was to assess the duration of DDI in ECS as well as its impact on neonatal outcome., Patients and Methods: Data from 437 patients at a single, tertiary care hospital were retrospectively analysed regarding influence on the duration of DDI. Subsequently the impact of DDI on neonatal outcome and incidence of adverse neonatal outcome was analysed., Results: DDI of ECS performed outside core working hours was significantly prolonged (p<0.001). Shorter DDI showed a statistically worse arterial cord blood pH (p=0.001, r=0.162) and base excess (p=0.05; r=0.094). Duration of DDI had no significant impact on the incidence of adverse neonatal outcome (p=0.123)., Conclusion: Awareness of influence on DDI might contribute to expediting DDI, but duration of DDI showed no impact on the incidence of adverse neonatal outcome. Data were not adequate to suggest a recommendation for DDI time standards., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Squamous cell carcinoma of the vulva (SQCV) is the fifth common cancer in women. Necessity of inguinal lymph node surgery depends on the depth of stromal invasion, inducing lymph node surgery, if depth of invasion is more than 1 mm. In this study we tested the prediction of stromal infiltration depth by measurements in preoperative biopsies., Methods: We analyzed whether a different operative strategy in respect to lymph node surgery would have been chosen based on the pre- or postoperative depth of stromal invasion for each patient. Examination of infiltration depth in preoperative biopsies and surgical specimen were compared., Results: In total 77 patients were included in this study. Of those 89.6% showed different depths of stromal invasion comparing the pre- and postoperative specimen. Within seventeen patients (22.1%) preoperative depth was 1 mm or less and a postoperative depth was > 1 mm., Conclusion: We pointed, that only in 77.9% of the patients who should have undergo lymph node surgery based on the postoperative depth of infiltration underwent this procedure. Consequentially in 22.1% of the cases a second operation could not be prevented with a preoperative taken biopsy as indicator for the necessity of lymph node surgery.

Background/aim: Surgical margin status remains an important determinant for recurrence of invasive breast cancer and ductal carcinoma in situ. We compared the number of positive margins in initial histology with rates of residual tumor in re-excision specimens. Furthermore, we analysed cost-effectiveness of re-excisions., Patients and Methods: 101 patients treated with secondary surgery were included. The first group underwent breast conserving surgery and secondary mastectomy. The second group was primarily treated with subcutaneous mastectomy followed by secondary surgery., Results: Within the first group, 22.7% did not show residual tumor in the re-excision specimen. Of the second group, 54.3% had no residual tumor. Consequentially 45.7% needed a re-excision to achieve R0 status. Cost-effectiveness was determined as secondary endpoint. If a patient needs a secondary mastectomy the hospital gains 602,65€ in comparison to a primary breast conserving operation., Conclusion: In every second patient who had first received a subcutaneous mastectomy, no tumor could be detected in the secondary operation despite a previous R1 status., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Numerous risk factors have been reported to influence the development of urinary incontinence (UI). In this study, we took a closer look on the different forms of UI and tried to identify differences in regard to potential risk factors. Of special interest was the onset of UI symptoms and its relation to menopausal status., Patients and Methods: This was a hospital-based analysis of patients who presented with urinary incontinence in the outpatient ward of a tertiary hospital. The diagnosis of urinary incontinence was based on the subjective complaints of patients. Data concerning menopausal status, hormone replacement therapy, prior hysterectomy were assessed., Results: The mean age was 53.8 years in the SUI group, 62.7 years in the MUI group and 66.1 years in the UUI group, respectively (p<0.001). The proportion of patients with UUI was higher in the postmenopausal group, whereas the proportion of SUI was higher in the premenopausal group (p<0.001). The mean age in which complaints occurred was significantly lower in the SUI group (45.4 years) compared to the MUI (51.0 years) and UUI groups (54.7 years) (p<0.001). There was no correlation between menopausal status and onset of urinary incontinence (p=0.143)., Conclusion: Additional anamnestic information help further characterize the different types of urinary incontinence that can lead to an optimization of treatment options. Younger age and premenopausal status were accompanied by milder forms of UI while menopausal status itself had no influence on the onset of UI symptoms indicating that age-related changes may lead to different types of incontinence., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Implant-based immediate breast reconstruction (IBR) is a common surgical procedure in breast cancer patients. Comparative analysis concerning the placement of implants is still lacking. Hence, we aimed to analyze pre- versus subpectoral IBR in breast cancer patients., Patients: A single-center experience with implant-based IBR following skin/nipple-sparing mastectomy was evaluated. Patient demographics, incidence of major complications, and quality of life assessed with BREAST-Q were compared between the pre- and subpectoral cohort., Results: A total of 63 patients were included in this analysis of whom 29 underwent subpectoral and 34 underwent prepectoral IBR. Median duration of surgery was prolonged in the subpectoral versus the prepectoral group (104 ± 28 vs. 80 ± 91 min; p < 0.05). The mean number of major complications was significantly increased in the subpectoral group (1.41 ± 1.76 vs. 0.47 ± 0.75 per patient; p < 0.05). Detailed analysis showed a significantly increased incidence of implant dislocation (p < 0.05) and a trend concerning capsular contracture (p = 0.086, not significant) and necrosis (p = 0.092, not significant) in the subpectoral group. Quality of life was equal in both groups., Conclusion: The mean number of major complications in the subpectoral group should be considered when IBR is indicated. Prepectoral IBR seems to be a feasible alternative surgical treatment option with less major complications in selected patients., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2019 by S. Karger AG, Basel.)

Background/aim: The aim of this study was to determine the value of Doppler indices and notching assessment of uterine artery between the 19th and 22nd week of gestation in the prediction of pregnancy outcome such as delivery mode, birth weight, Apgar score, afterbirth pH, fetal presentation, preeclampsia and fetal growth restriction in singleton pregnancy., Patients and Methods: This is a retrospective cohort study of Doppler ultrasound of the uterine arteries at 19-22 week of gestation in 1,472 women with singleton pregnancies., Results: Patients with bilateral high resistance-index (RI) and pulsatility-index (RI) or with the presence of a notch showed a significantly higher prevalence of small for gestational age (SGA) fetuses and intrauterine growth restriction (IUGR), low Apgar Scores at the 1st and the 5th min, high c-section rate, preterm birth, breech birth, placental insufficiency and placental abruption. The presence of a notch significantly increased the prevalence of severe preeclampsia, HELLP-syndrome and oligohydramnios. Also, patients with a bilateral uterine notching had a higher c-section rate along with higher prevalence of SGA and IUGR at screening time., Conclusion: Uterine artery Doppler waveform analysis as well as the assessment of the presence of a notch in the second trimester can be used as a screening method to identify women who will thereafter develop a severe adverse outcome., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The problem of adequately marking any given lesion within a breast surgical site is commonly solved by introducing a titanium clip. However, clip dislocation and/or stereotactic hook-wire dislocation are common problems. An ideal solution would be a clip that can be easily found without the use of stereotactic intervention. This work reviews the available data on radiofrequency identification devices (RFID) in breast surgery, reports initial experience data in Europe and discusses surgical pitfalls, advantages and disadvantages., Patients and Methods: This study represents a single center, consecutively recruited, initiation trial with subsequent surgeon questionnaire for the first institution in Europe to report Faxitron LOCalizer™ chip data. Four patients with non-palpable tumors were marked with the system and were correlated via mammography, pre- and intra-operative ultrasound and pathology. Data were then compared to available literature and a literature review was added., Results: The four patients marked with this RFID system, displayed a 100% success location rate at a 0% complication rate. Surgeons evaluated the new system as being safe to use and only slightly more difficult to place compared to a standard clip. A significant improvement in ultrasound localization and intraoperative localization was also reported for the LOCalizer™ system when compared to a standard titanium clip., Conclusion: This trial added a small number of consecutively recruited patients to an existing number of available data, resulting in a total of 121 evaluated and reviewed Faxitron LOCalizer™ marked non-palpable in-breast lesions worldwide., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: For many years clinical research has been concerned with doppler sonography as a non-invasive tool for intrauterine fetal status assessment. A new focus is now placed on the measurement of cerebroplacental index (CPR) as a predictor of fetal outcome. Our aim was to investigate the relationship between the cerebroplacental ratio (CPR), the delivery mode and the fetal outcome in singleton pregnancies., Patients and Methods: A retrospective cohort study of pregnancies in which doppler sonography of middle cerebral artery (MCA) and umbilical artery (UA) was conducted up to 9 weeks before delivery took place. Patients with pathological (CPR≤1.0) and normal CPR (>1.0) were compared by umbilical cord pH, APGAR scores, birth weight, delivery week and delivery mode., Results: A total of 2,270 singleton pregnancies were included. The APGAR score for 1, 5 and 10 minutes and the gestational age at delivery were significantly lower in the group of patients with pathological CPR (p<0.001). Overall, 50% of the cohort had a cesarean section, the difference between the groups was statistically significant (p<0.001), with a higher amount of cesareans in the group of patients with pathological CPR. The multiple regression analysis showed a significantly improved pH of delivery when cesarean section (p<0.001), female sex of fetus (p=0.013) and higher CPR (p=0.035) were present., Conclusion: The measurement of CPR is an important, non-invasive predictive parameter and leads to the identification of a risk collective even in the non-selected patient population and thus probably to a reduction of perinatal morbidity., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: BRCA1-deficient breast cancers carry a specific DNA copy-number signature (" BRCA1-like ") and are hypersensitive to DNA double-strand break (DSB) inducing compounds. Here, we explored whether (i) EZH2 is overexpressed in human BRCA1 -deficient breast tumors and might predict sensitivity to DSB-inducing drugs; (ii) EZH2 inhibition potentiates cisplatin efficacy in Brca1 -deficient murine mammary tumors., Experimental Design: EZH2 expression was analyzed in 497 breast cancers using IHC or RNA sequencing. We classified 370 tumors by copy-number profiles as BRCA1 -like or non- BRCA1 -like and examined its association with EZH2 expression. Additionally, we assessed BRCA1 loss through mutation or promoter methylation status and investigated the predictive value of EZH2 expression in a study population of breast cancer patients treated with adjuvant high-dose platinum-based chemotherapy compared with standard anthracycline-based chemotherapy. To explore whether EZH2 inhibition by GSK126 enhances sensitivity to platinum drugs in EZH2-overexpressing breast cancers we used a Brca1 -deficient mouse model., Results: The highest EZH2 expression was found in BRCA1-associated tumors harboring a BRCA1 mutation, BRCA1 -promoter methylation or were classified as BRCA1 like. We observed a greater benefit from high-dose platinum-based chemotherapy in BRCA1 -like and non- BRCA1 -like patients with high EZH2 expression. Combined treatment with the EZH2 inhibitor GSK126 and cisplatin decreased cell proliferation and improved survival in Brca1 -deficient mice in comparison with single agents., Conclusions: Our findings demonstrate that EZH2 is expressed at significantly higher levels in BRCA1 -deficient breast cancers. EZH2 overexpression can identify patients with breast cancer who benefit significantly from intensified DSB-inducing platinum-based chemotherapy independent of BRCA1 -like status. EZH2 inhibition improves the antitumor effect of platinum drugs in Brca1 -deficient breast tumors in vivo ., (©2019 American Association for Cancer Research.)

Purpose: Squamous cell carcinoma of the vulva (SQCV) is the fifth most common cancer in women and accounts for about 5% of all genital cancers in women. The PD-L1 signaling pathway is activated in many malignant neoplasms and its blockade enhances anti-cancer immunity. The aim of our study was to examine the protein expression of PD-L1 and PD-1 in squamous cell cancer of the vulva, its correlations with clinicopathologic features and prognostic value., Methods: Patients with SQCV treated in one institution were used for the analyses. PD-L1 immunohistochemistry was performed on 4 µm-thick section of the respective FFPE tissue blocks using the 28-8 antibody. PD-L1 scoring was performed separately for tumour cells (TC) and tumour associated immune cells. DNA was extracted to determine HPV status. Kaplan-Meier estimates for disease-free-survival and overall-survival were calculated and compared by log-rank test., Results: PD-L1 expression in tumour cells could be observed in 32.9% of the patients. The expression of PD-L1 in peritumoural immune cells was confirmed in 91.4% of the patients. A significant correlation between PD-L1 expression in tumour cells and tumour stage was detected (p = 0.007). PD-L1 expression was independent from HPV status. Using the log-rank test we could not prove any significant differences in disease-free survival (p = 0.434) and overall survival (p = 0.858). Regression analysis showed that nodal status is a predictive factor of survival (p < 0.001)., Conclusion: The present study showed that a relevant amount of patients with squamous cell cancer of the vulva express PD-L1 in both, tumour cells and tumour-associated immune cells. Furthermore, the significant correlation of PD-L1 expression in TCs with tumour stage indicated the clinical impact of PD-L1 expression during tumour development. These data indicate that SQCV might be amenable to immune checkpoint-inhibition and constitute a rational for the future clinical trials.

Background/aim: The aim of this study was to evaluate the difference in clinical outcomes in patients with histologically confirmed cervical cancer of the uterus treated with either laparoscopy or laparotomy with curative intent between 2011 and 2017 at the Department of Gynecology and Obstetrics of University Hospital Cologne., Materials and Methods: This retrospective analysis included all patients who received surgical treatment with curative intent between January 2011 and December 2017 for stages IA1 to IIB cervical carcinoma. Patients receiving primary or secondary surgery after neoadjuvant chemotherapy were also included., Results: In total, 75 patients were included, of whom 34 patients underwent minimally invasive surgery and 41 underwent open surgery. Neoadjuvant chemotherapy was performed in 10 patients in the minimally-invasive group and in 14 patients in the laparotomy group. Statistically, no significant difference in overall survival (OS) was observed in both groups. Disease-free survival showed a significant difference in favor of the minimally invasive group., Conclusion: Minimally invasive surgical therapy for cervical cancer improves disease-free-survival. Prospective trials are needed to further confirm these results., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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.

Background/aim: The aim of the present study was to analyze metastasized breast cancer (BC) patients with regard to the discordance of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). We especially aimed to analyze the association between the change of tumor biology and previous treatment or metastatic sites., Patients and Methods: Patients with metastasized BC who were treated at the Department of Gynecology/Breast Center of the University Hospital of Cologne were analyzed., Results: Loss of HER2 occurred more frequently in lymph node metastases that were not in the axillary region (p=0.026). Letrozole showed a significant correlation with loss of ER and/or PR (p=0.041). Improved overall survival and post-metastasis survival were noticed with a gain of HER2 (p=0.044 and p=0.009, respectively) and concordant positive ER and PR status (p=0.002 and p=0.001, respectively)., Conclusion: The discordance of receptors and the dependence of BC on therapies as well as metastatic sites stresses the necessity of early sample taking to offer patients suitable therapy options., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Clinical data concerning synthetic meshes in comparison to acellular dermal matrices (ADMs) in breast reconstruction are limited. Also, direct comparisons between titanium-coated polypropylene mesh and partially absorbable polypropylene mesh have not yet been reported., Materials and Methods: This analysis represents a retrospective, single-surgeon, multi-center study of 320 cases using either TiLoop Bra/TiMesh® (n=192) or Seragyn® (n=128) in breast reconstruction. Results were compared with ADM-based reconstructions (Epiflex® and SurgiMend®)., Results: Major complication rates (i.e. revision surgery) occurred in 3.9% (Seragyn®) and 8.3% (TiLoop Bra/TiMesh®) of all cases. Minor complications occurred in 18% (Seragyn®) and 8.9% (TiLoop Bra/TiMesh®). Subgroup analysis showed red breast syndrome to occur more often in the Seragyn group (3.9% Seragyn® vs. 0.5% TiLoop Bra/TiMesh®, p<0.05)., Conclusion: TiLoop Bra/TiMesh® and Seragyn® do not differ significantly in complication rates. There was no difference in performance when compared to ADMs., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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.)

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.)

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.

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.

Purpose: Mastectomy is the standard procedure in patients with in-breast tumor recurrence (IBTR) or breast cancer after irradiation of the chest due to Hodgkin's disease. In certain cases a second breast conserving surgery (BCS) in combination with intraoperative radiotherapy (IORT) is possible. To date, data concerning BCS in combination with IORT in pre-irradiated patients are limited. This is the first pooled analysis of this special indication with a mature follow-up of 5 years., Methods: Patients with IBTR after external beam radiotherapy (EBRT; treated in two centers) for breast cancer were included. Patients with previous EBRT including the breast tissue due to other diseases were also included. IORT was performed with the Intrabeam™-device using low kV X-rays. Clinical data including outcome for all patients and toxicity for a representative cohort (LENT-SOMA scales) were obtained. Statistical analyses were done including Kaplan-Meier estimates for local recurrence, distant metastasis and overall survival., Results: A total of 41 patients were identified (39 patients with IBTR, 2 with Hodgkin`s disease in previous medical history). Median follow-up was 58 months (range 4-170). No grade 3/4 acute toxicity occurred within 9 weeks. Local recurrence-free survival rate was 89.9% and overall survival was 82.7% at 5 years. Seven patients developed metastasis within the whole follow-up., Conclusions: BCS in combination with IORT in IBTR in pre-irradiated patients is a feasible method to avoid mastectomy with a low risk of side effects and an excellent local control and good overall survival.

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.)

Introduction: This study aimed to determine the effects of induction of labour in late-term pregnancies on the mode of delivery, maternal and neonatal outcome., Methods: We retrospectively analyzed deliveries between 2000 and 2014 at the University Hospital of Cologne. Women with a pregnancy aged between 41 + 0 to 42 + 6 weeks were included. Those who underwent induction of labour were compared with women who were expectantly managed. Maternal and neonatal outcomes were evaluated., Results: 856 patients were included into the study. The rate of cesarean deliveries was significantly higher for the induction of labour group (33.8 vs. 21.1 %, p < 0.001). Aside from the more frequent occurrence of perineal lacerations (induction of labour group vs. expectantly managed group = 38.1 % compared with 26.4 %, p = 0.002) and all types of lacerations (induction of labour group vs. expectantly managed group = 61.5% vs. 52.2 %, p = 0.021) in women with vaginal delivery, there were no significant differences in maternal outcome. Besides, no differences regarding neonatal outcome were observed., Conclusions: Our study suggests that induction of labour in late and postterm pregnancies is associated with a significantly higher cesarean section rate. Other maternal and fetal parameters were not influenced by induction of labour.

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.