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Mucinous ovarian carcinoma (mOC) is a rare subtype with distinct clinical characteristics and biological behavior that differentiate them from other epithelial ovarian cancers. This study aimed to evaluate BMI-1 expression as a potential target for therapeutic approaches in advanced stage mOC.We performed gene set, as well as transcription factor enrichment analysis and immunohistochemistry assessing of the BMI-1 protein levels in tissue specimens of eighteen mucinous ovarian cancer patients. To validate the clinical relevance of the findings, we performed cell viability assays and western blot analysis utilizing high-grade serous (HGSC) and mOC cell lines.BMI1 expression was not significantly associated with patient age, FIGO stage, lymph node status, and family history. With regard to progression-free survival, there was also no significant association (p=0.418). Cell viability was significant decreased in response to carboplatin in HGSC cells TYK-nu and OVHASO, and in mOC cell lines COV644 and EFO-27. Western blot analysis demonstrated various expression levels across all cell lines.BMI-1 could be a useful potential therapeutic target in some ovarian cancer patients, including mOC patients.

Objectives: The aim of this study was to determine if a long versus short interval between preoperative uterine artery embolization (PUAE) and subsequent myomectomy impact perioperative blood loss and the complication rate in cases of enlarged multi-fibroid uterus. Design: In cases of an enlarged multi-fibroid uterus, operative myomectomy can lead to heavy blood loss and consequently increases the risk for transfusion and hysterectomy. PUAE can possibly contribute to a reduction of these risks. Our study was designed to determine if a long versus short interval between PUAE and subsequent surgery impacts perioperative blood loss and complication rate. Participants and Methods: PUAE was performed 24 h before the planned myoma enucleation in 21 patients between January 2011 and March 2016 (group 1) or 19 days before the operation in 23 patients from March 2016 to May 2018 (group 2). A comparison was made to a historical sample of 57 patients with large myomas (>10 cm) without PUAE (group 3). Perioperative blood loss, need for postoperative blood transfusion, and postoperative complications were recorded. Subjective improvement of myoma-related symptoms was assessed for each group by a questionnaire. Results: PUAE was carried out successfully without complications in all patients. Conversion to hysterectomy was not needed in any of the PUAE patients but was necessary in one of the control patients. In the three groups’ comparison, there was a significant lower risk for high blood loss (≥500 mL) in group 1 and a lower but not significant lower risk in group 2 compared to group 3 without an embolization preoperatively. Also, a significant lower risk for postoperative blood transfusion for group 1 (OR 0.02; 0.001–0.328; p = 0.01) and 2 (OR 0.02; 0.001–0.277; p = 0.01) compared to group 3 was observed. The postoperative complication risk was lower in group 2 (model 1: OR 0.12; 0.016–0.848; p = 0.03; model 2 OR 0.07; 0.009–0.588; p = 0.01) compared to group 3. In the context of the postoperative questionnaire, 10 of 11 patients in group 1, 12 of 12 patients in group 2, and 31 of 36 patients from the control group reported an improvement of their complaints. Conclusion: PUAE is beneficial for uterus-preserving removal of myomas from patients with a substantially enlarged uterus. There is a significant reduction of high blood loss (≥500 mL), need for postoperative blood transfusion, and postoperative complications in patients with extensive fibroid disease after PUAE compared to no intervention before myoma enucleation.

Background To evaluate the diagnostic value of adding human epididymis protein 4 (HE4), cancer antigen 125 (CA125) and risk of malignancy algorithm (ROMA) to ultrasound for detecting ovarian cancer in patients with a pelvic mass. Methods This was a prospective, observational, multicenter study. Patients aged > 18 years who were scheduled to undergo surgery for a suspicious pelvic mass had CA125 and HE4 levels measured prior to surgery, in addition to a routine transvaginal ultrasound scan. The diagnostic performance of CA125, HE4 and ROMA for distinguishing between benign and malignant adnexal masses was assessed using receiver operating characteristic (ROC) analysis and the corresponding area under the curve (AUC). Results Of 965 evaluable patients, 804 were diagnosed with benign tumors and 161 were diagnosed with ovarian cancer. In late-stage ovarian cancer, CA125, HE4 and ROMA all had an excellent diagnostic performance (AUC > 0.92), whereas in stage I and II, diagnostic performance of all three biomarkers was less adequate (AUC Conclusions ROMA and HE4 could be valuable biomarkers to help with the diagnosis of ovarian cancer in premenopausal patients in order to differentiate from endometriosis, whereas CA125 may be more adequate for postmenopausal patients.

ObjectiveWomen living with HIV have an increased risk of human papillomavirus (HPV) infection and cervical cancer. Little is known about genotype-specific HPV prevalence, the impact of antiretroviral therapy, immunological status, and additional risk factors in women living with HIV in Germany. The goal of this study was to characterize the risk profile for cervical dysplasia in these women.MethodsPatients with HIV infection presenting at Charité-Universitätsmedizin Berlin from October 2017 to September 2020 were included and underwent gynecological examination, colposcopy, cervical cytology and HPV genotype testing. HPV genotypes were stratified by carcinogenicity. Atypical squamous cells of undetermined significance or higher were considered abnormal cytology. Data were analyzed by SPSS software (version 26, 2019). A two-tailed p-value ≤0.05 was considered statistically significant.ResultsA total of 84 women were evaluated. The majority (95.2%) received antiretroviral therapy. Median CD4 cell count was 564 cells/µl (range 20–1969). 95.2% were previously screened for cervical cancer. High-risk HPV prevalence was 44%. High-high-risk HPV subtypes (16, 18, 31, 33, 45, 52, 58) were significantly associated with abnormal cytology (pConclusionsAntiretroviral therapy and adherence to cervical cancer screening was high. High-high-risk HPV, especially HPV16, coincided with high incidence of cytological abnormalities. Women living with HIV in Germany have adequate immune status and are often pre-screened for cervical cancer, and therefore have a different risk profile for cervical dysplasia than in low-income or medium-income countries. Adapted screening programs should be defined.

The prognosis for ovarian cancer patients remains poor. A key to maximizing survival rates is early detection and treatment. This requires an accurate prediction of malignancy. Our study seeks to improve the accuracy of prediction by focusing on early subjective assessment of malignancy. We therefore investigated the assessment of patients themselves in comparison to the assessment of physicians.One thousand three hundred and thirty patients participated in a prospective and multicenter study in six hospitals in Berlin. Using univariate analysis and multivariate logistic regression models, we measured the accuracy of the early subjective assessment in comparison to the final histological outcome. Moreover, we investigated factors related to the assessment of patients and physicians.The patients' assessment of malignancy is remarkably accurate. With a positive predictive value of 58%, the majority of patients correctly assessed a pelvic mass as malignant. With more information available, physicians achieved only a slightly more accurate prediction of 63%.For the first time, our study considered subjective factors in the diagnostic process of pelvic masses. This paper demonstrates that the patients' personal assessment should be taken seriously as it can provide a significant contribution to earlier diagnosis and thus improved therapy and overall prognosis.

ObjectiveLow grade serous ovarian cancers characterize a unique clinical pattern and likely less frequent incidence of lymphatic metastasis. The expression level of Ki67 is associated with differences in prognosis and therapy outcome. However, its expression in combination with lymphovascular space invasion has not been evaluated in the prediction of lymphatic metastasis.MethodsPatients with low grade serous ovarian cancer were identified in an institutional database. Patients with primary low grade serous ovarian cancer diagnosed and/or treated at our center between September 2000 and December 2018 were identified. Receiver operator characteristics curve analysis was performed to find the cut-off values of per cent Ki67 to discriminate patients with lymph node metastasis. The association between the presence of lymphovascular space invasion and lymph node involvement was analyzed.ResultsA total of 109 patients with primary low grade serous ovarian cancer were identified in our institution's database. Of these, 72 (66.1%) patients underwent primary surgery with pelvic and para-aortic lymph node dissection. Complete data for Ki67 expression and lymphovascular space invasion were obtained for 61 (84.7%) of these patients. Among them, 37 (60.7%) patients had lymph node metastasis. The presence of lymphovascular space invasion was associated with an increased risk of lymph node metastases (odds ratio (OR)=12.78, 95% confidence interval (CI) 3.15 to 51.81; p65 years, peritoneal carcinomatosis, and ascites>500 mL, lymphovascular space invasion remained a significant risk factor for lymphatic metastases (OR=35.11, 95% CI 2.38 to 517.69; p=0.010). Ki67 ≥6% was associated with a higher risk of lymphovascular space invasion (OR=3.67, 95% CI 1.26 to 10.64; p=0.017). No significant correlation between Ki67 expression level and nodal metastases was found (OR=2.19, 95% CI 0.76 to 6.26; p=0.14). Neither presence of lymphovascular space invasion or nodal metastases was associated with a statistically poorer prognosis.ConclusionsWe showed an association between lymphovascular space invasion, Ki67 expression, and risk of lymph node metastasis in primary low grade ovarian cancer. Further prospective trials evaluating lymphovascular space invasion and Ki-67 as predictors of lymph node metastasis are needed.

Purpose The aim of this study was to investigate preoperative quality of life (QoL) as a predictive tool for severe postoperative complications (POC) in gynecological cancer surgery. Methods This is a prospective study of patients undergoing gynecologic cancer surgery at an academic center in Germany. QoL was assessed by the EORTC Quality of Life Questionnaire (QLQ-C30) and the NCCN Distress Thermometer (DT). Several geriatric assessment tools have been applied. POC were graded using Clavien–Dindo criteria. Using multivariable logistic regression models, we identified predictive clinical characteristics for postoperative complications. Results Within 30 days of surgery, 40 patients (18%) experienced grade ≥ 3b complications including 9 patients (4%) who died. The dominant complication was anastomosis insufficiency with 13 patients (5.8%). In the multivariable stepwise logistic regression through all univariate significant variables, we found that impaired physical functioning was predictive of POC, defined by an EORTC score p 20 (OR 3.08, 95% CI 1.15–8.26, p = 0.025) indicated a significant predictive value. Being overweight or obese (BMI > 25) were also identified as predictive factors (OR 5.44, 95% CI 2.04–14.49, p = 0.001) as were reduced Mini Mental State Examination (MMSE) results p = 0.02). Conclusion Preoperative QoL measurements could help to predict postoperative complications in patients with gynecological cancer. Patients with limitations of mobility, debilitating symptoms and cognitive impairment have an increased risk for developing severe POC.

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

ObjectivePrediction of post-operative residual disease after ovarian cancer cytoreductive surgery remains a topic of interest to gynecologic oncologists. The aim of this study was to explore the correlation between serum CA125, peritoneal cancer index, and intra-operative mapping of ovarian cancer and their predictive value for post-operative outcome.MethodsA total of 70 patients with primary epithelial ovarian cancer, who underwent primary cytoreductive surgery at Charité, Berlin between January 2013 and February 2014 were included. In all patients, pre-operative CA125 values, intra-operative peritoneal cancer index, and intra-operative mapping of ovarian cancer were determined.ResultsUsing a receiver operating characteristic analysis, cut-off values for CA125, peritoneal cancer index, and intra-operative mapping of ovarian cancer score could be defined. Patients with pre-operative serum CA125 >600 U/mL had a three times higher risk for residual tumor after primary cytoreductive surgery (p=0.037). A peritoneal cancer index score >20 indicated a nine times increased risk for residual tumor (p=0.003). More than six affected abdominopelvic fields on the intra-operative mapping of ovarian cancer was associated with a 25 times higher risk of residual tumor after primary cytoreductive surgery (p≤0.05). The combination of all three values predicted residual tumor in up to 90% of patients.ConclusionWe found that pre-operative CA125 >600 U/mL, peritoneal cancer index >20, and intra-operative mapping of ovarian cancer score >6 could be used as predictors of complete tumor resection. The combination of all these three values predicted the incomplete resection of disease in up to 90% of patients even in experienced centers.

Objective Low-grade epithelial ovarian cancers (EOC), constitute the minority among all epithelial cancers. Our study objective was to focus on low-grade recurrent EOC and compare the survival with high-grade disease, as well as in regard to “platinum-sensitive” and “-resistant” recurrences according to platinum-free interval. Methods This is an exploratory analysis within the North-Eastern German Society of Gynecological Oncology (NOGGO) database including five randomized phase II/III trials comparing different chemotherapy regimens in recurrent EOC. We conducted survival analyses and cox-proportional regression models. Results Out of 1050 patients having the first recurrence, 42 (4%) patients had low-grade and 1008 (96%) patients had high-grade disease. In the subgroup of platinum-sensitive recurrences, progression-free survival (PFS) (8.7 m vs 9.7 m, p = 0.7) and overall survival (OS) (23.9 m vs 24.8 m, p = 0.9) did not differ between low-grade and high-grade diseases. In platinum-resistant recurrences, patients with low-grade ovarian cancer had significantly better PFS (7.6 m vs 3.6 m, p = 0.03) and OS (41.9 m vs 9.5 m p = 0.002) in comparison to those with high-grade cancer. At low-grade EOC, there were no significant PFS (p = 0.91) and OS (p = 0.25) differences between platinum-sensitive and –resistant recurrences. Patients with low-grade non-serous histology had lower PFS with compared to those with low-grade serous histology (p = 0.004). At cox regression analysis presence of ascites and residual disease after secondary cytoreductive surgery were independently associated with poor PFS within low-grade recurrent EOC. Conclusion Our study indicates, platinum-free interval does not have any prognostic significance at recurrent low-grade EOC and non-serous histology is associated with poorer outcome in recurrence. Secondary surgical cytoreduction to no-gross residual disease and ascites are independently associated with disease progression.

Introduction: The aim of this study was to explore a possible relation between myoma-related anxieties and general state or trait anxiety or psychological distress, to get a better understanding of...

OBJECTIVE Patients with platinum-resistant ovarian cancer (PROC) have a high need for reliable prognostic markers. Since significance of primary platinum resistance (PPR) versus secondary platinum resistance (SPR) was identified for patients receiving anti-angiogenic therapy, it has not been confirmed for chemotherapy only. METHODS PROC patients from 3 prospective trials of the NOGGO study group (TOWER, NOGGO-Treosulfan, and TRIAS) were included in this meta-analysis. Exploratory Cox and logistic regression analyses were performed to correlate progression-free survival (PFS) and overall survival (OS) with the timing when platinum resistance developed. RESULTS Of 477 patients, 264 (55.3%) were classified as PPR, compared to 213 (44.7%) with SPR. For patients receiving chemotherapy only, SPR was associated with a significantly longer median PFS of 3.9 compared to 3.1 months for PPR (hazard ratio HR=0.78; p=0.015). SPR versus PPR was confirmed to be an independent prognostic factor for better PFS in multivariate analysis (HR=0.74; p=0.029). Benefit from adding sorafenib to chemotherapy was mainly seen in PPR (HR=0.40; p{\textless}0.001) compared to SPR patients (HR=0.83; p=0.465). CONCLUSIONS Prognostic significance of SPR versus PPR could be elucidated for patients receiving chemotherapy only. In contrast to bevacizumab, the multi-kinase inhibitor sorafenib exhibits profound therapeutic efficacy in PPR patients indicating potential to overcome this negative prognostic impact.

Background: Complete macroscopic tumor resection is the strongest prognostic factor for patients with ovarian cancer, which requires complex surgery for achievement. Based on the mostly advanced tumor stage and high symptom burden many patients are classified as frail which may limit optimal surgical outcome. Aim of this study is to evaluate the predictive ability of Frailty Index for surgical outcomes in patients with ovarian cancer. Methods: This prospective study enrolled patients with ovarian cancer undergoing cytoreductive surgery. We classified frailty proposed by Mitnitski et al. regarding the cumulative deficit model of frailty. Utilizing Receiver Operator Characteristic (ROC) analysis and logistic regression, we determined predictive clinical factors for severe postoperative complications. The Kaplan-Meier method and log-rank test were used for overall survival analysis. Results: Out of f 144 enrolled patients, the overall prevalence of frailty based on a Frailty Index >0.26 and Frailty Index >0.15 was 33% and 74%, respectively. The logistic regression shows that frail patients with a Frailty Index >0.26 (Odds ratio (OR): 3.64, 95% CI: 1.34–9.85, p = 0.01), ECOG PS > 1 (OR 6.33, 95% CI:1.31–30.51, p = 0.02) and high surgical complexity score (OR 8.86, 95% CI:1.88–41.76, p = 0.006) had a significant higher risk for severe postoperative complications. According to multivariable cox regression Frailty Index >0.15 (hazard ratio (HR) (HR 1.87, 95% CI: 1.01–3.47, p = 0.048), residual tumor 1 cm (HR 5.00, 95% CI: 2.74–9.13, p < 0.001) and albumin 1 and recurrent surgery, Frailty Index >0.26 is associated with severe postoperative complications in patients with ovarian cancer. Besides tumor residuals and low albumin levels a Frailty Index >0.15 predicts poor survival. © 2021, AstraZeneca Roche, This study was funded by the ALLIMOGI-Foundation ., MGI reports grants from ALLIMOGI-Foundation during the conduct of the study; JS reports other from Medac, Roche, AstraZeneca, PharmaMar, personel fee and others outside the submitted work; HWs travel expenses were sponsored by Medac. The other authors declare no conflict of interest.

Background Accompanying co-morbidities in patients with ovarian cancer are of major relevance for scheduling debulking surgery, especially in the anesthesiological consultations. Aim of this study was to evaluate the impact of co-morbidities and patient characteristics on postoperative complications. Methods Patients undergoing maximal cytoreductive surgery were prospectively enrolled from October 2015 to January 2017. Various variables were recorded, such as the Charlson comorbidity index, Eastern cooperative oncology group scale of performance status (ECOG PS) and the American society of anesthesiologists physical status classification system (ASA PS). Surgical complications were graded using the Clavien–Dindo criteria. Logistic regression models were used to analyze risk factors for severe postoperative complications. Results Of 106 enrolled patients, 19 (17.9%) developed severe postoperative complications grade ≥ IIIb according to Clavien–Dindo criteria. In the multivariable regression analysis impaired (ECOG PS) > 1 (odds ratio OR) 13.34, 95% confidence interval (CI) 1.74–102.30, p = 0.01), body mass index (BMI) > 25 kg/m2 (OR 10.48, 95% CI 2.38–46.02, p = 0.002) along with the use of intraoperative norepinephrine > 0.11 µg/kg/min (OR 4.69, 95% CI 1.13–19.46, p = 0.03) and intraoperative fresh frozen plasma (FFP) > 17 units (OR 4.11, 95% CI 1.12–15.14, p = 0.03) appeared as significant predictors of severe postoperative complications. Conclusion We demonstrated that neither the presence of a certain comorbidity nor the summation of the co-morbidities were associated with adverse outcome. Patient characteristics, such as ECOG PS > 1 and obesity (BMI > 25 kg/m2), are highly predictive factors for severe postoperative complications. The analysis of intraoperative data showed that the need for more than > 0.11 µg/kg/min of norepinephrine and transfusions of FFPs more than 17 units were strongly associated with severe postoperative complications.

AIM To demonstrate the prognostic value of pleural carcinosis/effusion in a cohort of patients with advanced epithelial ovarian cancer (EOC) and the associated therapeutic implications. PATIENTS AND METHODS Overall, data for 388 patients with EOC with confirmed malignant pleural effusion (MPE) or pleural carcinosis were retrospectively analyzed. Exclusion criteria were non-epithelial ovarian malignancies and presence of other comorbidities associated with pleural effusions. RESULTS The prognosis after the occurrence of MPE during the EOC in relapsed cases was poor with an overall survival of 9.9 months. In the multivariate analysis, the time point of the manifestation of the pleural effusion (p

BackgroundA Total Retroperitoneal en bloc resection Of Multivisceral-Peritoneal packet (TROMP operation) is a no-touch isolation technique in a retroperitoneal space to resect the parietal peritoneum and the affected organs in advanced ovarian cancer. The study prescribed and analysed the results of this novel technique for primary cytoreductive surgery.MethodsThe study included 208 patients operated between January 2015 and December 2017 in Charité, Berlin. The TROMP operation was performed in 58 patients, whereas the other 150 patients were operated with the conventional cytoreductive method.ResultsThe complete tumor resection rate accounts for 87.9% in TROMP group and 61.3% in the conventional surgery group. (p=0.001). This difference was even stronger in the sub-group of very advanced stages (T3c+T4) (85.1% of TROMP group and in only 53.1% in the conventional surgery group, p=0.001). The duration of the primary cytoreductive surgery was about 33 minutes shorter in TROMP group (median: 335 minutes vs 368 minutes; TROMP vs conventional, respectively) in spite of the fact that the most advanced cytoreductive procedures were performed statically significant more in TROMP operation arm in comparison with the conventional surgery arm. There was no statistically significant difference between the groups regarding the postoperative complication, blood loss or the length of stay in intensive care unit.ConclusionTotal retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP operation) is a feasible and very effective technique of surgical therapy in advanced ovarian cancer. This technique increased the complete tumor resection rate to 87.9% without increasing the blood loss, postoperative complications or the duration of surgery. A prospective randomized study is advised to validate these results.

BackgroundSurgery for gynecological cancer involves highly invasive and complex procedures potentially associated with various complications, which can cause extended hospital stays and delay of subsequent therapy, with a detrimental effect on the prognosis. The aim of this study was to explore and define the predictors of severe postoperative complications in patients undergoing surgery for gynecologic cancer.MethodsPatients undergoing surgery for gynecologic cancers were analyzed prospectively from October 2015 through January 2017. Using validated assessment tools preoperatively, we assessed comorbidities, performance status, quality of life, nutritional and body composition by bioelectrical impedance analysis, and the surgical data of each patient. Surgical complications were graded using the Clavien-Dindo criteria. Using stepwise logistic regression models, we identified predictive markers for postoperative complications.ResultsOf the 226 enrolled patients, 40 (17.7%) experienced a grade ≥IIIb complication according to the Clavien-Dindo criteria. In the regression analysis, overweight/obesity (body mass index >25) (OR 6.41, 95% CI 2.38 to 17.24; p1 (OR 2.51, 95% CI 1.06 to 5.92; p=0.04). Intraoperative factors associated with higher risk of postoperative complications were increased use of norepinephrine (>11 µg/kg/min) (OR 5.59, 95% CI 2.16 to 14.44; pConclusionIn patients undergoing surgery for gynecological cancer, preoperative evaluation of performance status according to ECOG, domains of quality of life and nutritional status, as well as intraoperative monitoring of risk factors, might help to identify patients at high risk for severe postoperative complications, and thus reduce surgical morbidity and mortality.

The daily ingestion of green tea extract (GTE) capsules in women with oligo- or asymptomatic uterine myomas was monitored over 6 months with regard to their quality of life, myoma-associated complaints and side effects. The participants were interviewed and examined at the beginning of the study (T1) and then again after 6 months (T3). Quality of life was assessed using a SF-12 questionnaire while their myoma-associated complaints were ascertained by using a self-developed myoma symptom questionnaire. Changes in the size of the myomas were evaluated by vaginal sonography. Side effects after 3 months (T2) and 6 months were documented by systematic interviews. Overall; 25 participants (median 45 years) have been enrolled. The analysis of the SF-12 questionnaire showed a significant improvement of the physical cumulative score of the SF-12 during the 6 month GTE capsule ingestion (T1: mean value (M) = 52.731; 95% confidence interval (KI95%): 49.791–55.671; T3: M = 55.862; KI95%%: 55.038–56.685; p = 0.019). However, the mental cumulative score of the SF-12 did not change significantly (p = 0.674). No significant correlation could be established between the capsule ingestion and changes in the symptom questionnaire, the laboratory parameters nor the myoma size. No relevant adverse side effects were reported. Women who took GTE capsules showed a significant improvement in their physical cumulative score on the SF-12, but not in the global QoL score. Myoma size or other objective parameters did not change.

In this investigation of hospitalized cases of HG and subsequent births, we examine differences between patients who have and who have not experienced migration as well as the effect of HG on perinatal outcome.Retrospective quantitative data of hospitalized patients suffering from HG (1997-2015) was analyzed. Also analyzed was a retrospective record of perinatal data on a subgroup of patients (2002-2016), and a control group (matched pairs) based on the register of births created.1103 women with HG were hospitalized; in 434 cases birth outcome data could be evaluated as well. Migrants suffer from HG earlier in pregnancy; they are, however, less frequently exposed to psychosocial stress (according to anamnestic data). HG patients are younger and have more multiple pregnancies; the newborns are lighter (-70g) but have fewer congenital malformations (aOR 0.32, 95% CI 0.11-0.96) and are less frequently in need of treatment on the neonatology ward (aOR 0.59, 95% CI 0.36-0.97).Pregnant migrants are a special risk group for HG, possibly because of migration-caused stress. With severe HG, there are no adverse outcomes on the rest of the pregnancy.Unterscheiden sich stationär behandelte Hyperemesis gravidarum (H.g.)-Fälle in Abhängigkeit von einem Migrationshintergrund (MH)? Beeinflusst eine H.g den Geburtsausgang?Retrospektive monozentrische Datenanalyse zwischen 1997 und 2015 stationär behandelter Patientinnen mit H.g.; Erfassen von Schwangerschaftsparametern und Daten zum Klinikaufenthalt sowie zum Geburtsverlauf (Subgruppe).Bei 434 von 1103 stationär behandelten Schwangeren konnte auch auf geburtshilfliche Daten zurückgegriffen werden. Der Anteil von Frauen mit MH im H.g.-Kollektiv war überproportional hoch, sie wurden früher in der Schwangerschaft wegen H.g. stationär aufgenommen, waren seltener psychosozialem Stress (laut anamnestischen Angaben) ausgesetzt. H.g.-Patientinnen insgesamt sind jünger und haben häufiger Mehrlingsschwangerschaften. Die Neugeborenen von H.g.-Patientinnen sind leichter (−70g), haben weniger kongenitale Fehlbildungen (aOR 0,32, 95%CI 0,11−0,96), müssen seltener post natum auf einer Neugeborenenstation behandelt werden (aOR 0,59, 95%CI 0,36−0,97).Es zeigten sich keine relevanten negativen Auswirkungen einer H.g. auf den Geburtsausgang. Schwangere mit MH sind eine besondere Risikogruppe für H.g.

Aim of this study is to evaluate the predictive ability of Fried Frailty Score for surgical outcomes in patients undergoing gynecologic cancer surgery.This is a prospective cohort study at an academic gynecological cancer center from Oct 2015 through Jan 2017. We applied systematically numerous screening tools, geriatric questionnaires and single measurements which may provide predictions for surgical outcomes. We classified frailty according to the Fried definition and surgical complications were graded according Clavien-Dindo criteria. Using logistic regression analysis, we identified predictive clinical variables for postoperative complications (POC).Overall 226 patients were enrolled (median age 59 years, range 18-87 years). The prevalence of frailty based on the presence of three or more frailty criteria was 14.2%, the presence of one or two frailty criteria was classified as prefrail with 59.4% and without any presence as robust with 26.5%. Within 30 days of surgery, nine (3.8%) patients have died and 40 (18.3%) experienced a grade ≥ IIIb complication. In the regression analysis obesity (OR: 5.37, 95% CI 1.99-14.49, p = 0.001) as well as ECOG1 (OR: 4.32, 95% CI 1.28-1.55, p = 0.018) and Albumin3.6 g/dl (OR: 3.88, 95% CI 1.37-10.98, p = 0.011) emerged as significant predictors of postoperative complications (POC). Fried Frailty Score (OR: 2.41, 95% CI 0.91-6.41, p = 0.077) showed no significant additional predictive value.Fried Frailty Score could help the surgeon to estimate the risk for POC among patients undergoing gynecologic cancer surgery. But preoperatively determined ECOG, BMI and Albumin can predict severe POC in patients undergoing gynecologic surgery more precisely and should be assessed routinely.

AIM The purpose of the study was to evaluate whether preoperative cancer antigen 125 (CA-125) levels predict outcome of secondary cytoreductive surgery (SCS) in patients with serous recurrent ovarian cancer and whether this could be used as a prognostic factor for progression-free (PFS) and overall (OS) survival. PATIENTS AND METHODS A cohort of 111 patients with first recurrence of platinum-sensitive serous ovarian cancer, who had undergone SCS at the Department of Gynecology and Oncological Surgery, Charite, Campus Virchow Clinic was analyzed in correlation with the preoperative CA-125 value. RESULTS The median preoperative CA-125 level was 164 U/ml. Complete tumor resection was achieved in 58.6% of the patients. PFS and OS for patients with preoperative CA-125 of less than 164.5 U/ml was significantly better than those with preoperative CA-125 ≥164.5 U/ml (p=0.025 and p

BACKGROUND Despite many years of clinical research and development, nausea and vomiting remain challenging toxicities related to chemotherapy. The aim of our study was to clarify the significance of non-pharmacological, patient-related risk factors for chemotherapy-induced nausea and vomiting. Furthermore, we aimed to develop a unique patient-related risk score predicting nausea and vomiting in patients with gynaecological malignancies under chemotherapy. MATERIALS AND METHODS Based on a literature research, 27 risk factors were identified and a preliminary questionnaire was generated. This questionnaire was assessed in 20 patients diagnosed with gynaecological malignancies. RESULTS The majority of questions were easy to understand and could be answered unambiguously. Questions regarding alcohol consumption and nutrition needed optimization due to problems with suitable answer option finding. CONCLUSION Patient-related factors are currently not included when selecting antiemetic prophylaxis in patients under chemotherapy. After a few amendments, our questionnaire will be used in prospective study. To our knowledge, this is the first practicable questionnaire addressing these issues.

Backround The primary aim of this study was to investigate information needs and treatment preferences of patients with ovarian cancer, focusing especially on physician–patient relationship and treatment. Patients and methods A questionnaire was developed based on the experiences of the national German survey ‘Expression II’, and was provided to patients with ovarian cancer either at initial diagnosis or with recurrent disease via Internet (online-version) or as print-out-version. Results From December 2009 to October 2012, a total of 1830 patients with ovarian cancer from eight European countries (Austria, Belgium, France, Germany, Italy, Poland, Romania, Spain) participated, 902 (49.3%) after initial diagnosis and 731 (39.9%) with recurrent ovarian cancer. The median age was 58 years (range 17–89). Nearly all patients (96.2%) had experienced upfront surgery followed by first-line chemotherapy (91.8%). The majority of patients were satisfied with the completeness and comprehensibility of the explanation about the diagnosis and treatment options. The three most important aspects, identified by patients to improve the treatment for ovarian cancer included: ‘the therapy should not induce alopecia’ (42%), ‘there must be more done to counter fatigue’ (34.5%) and ‘the therapy should be more effective’ (29.7%). Out of 659 (36%) patients, who were offered participation in a clinical trial, 476 (26%) were included. Conclusion This study underlines the high need of patients with ovarian cancer for all details concerning treatment options irrespective of their cultural background, the stage of disease and the patient’s age. Increased information requirements regarding potential side effects and treatment alternatives were recorded. Besides the need for more effective therapy, alopecia and fatigue are the most important side effects of concern to patients.

Objective: Myomas are one of the most common tumors of the lower abdomen in women. At present, sonography and clinical examination are the prevalent diagnostic standards for these tumors, and no biomarkers have been established yet. The primary aim of this study was to determine if the surgical removal of myomas leads to a drop of lactate dehydrogenase (LDH), CA 125, and/or insulin-like growth factor (IGF-1) and therefore if these parameters are suitable as potential biomarkers for the presence or recurrence of a myoma. Study Design: The blood levels of LDH, CA 125, and IGF-1 were determined in 83 patients (age 18–50) with a verified diagnosis of myomas and surgical therapy at 3 different timepoints: preoperative (T0), 2 days postoperative (T1), and 6 months postoperative (T2). Vaginal sonography was performed preoperatively and once again at 6 months postoperatively. Results: The median (Q1–Q3) LDH values dropped significantly postoperatively: 239 (217–266) U/L at T0 versus 217 (190–255) U/L at T1, p < 0.001. The median (Q1–Q3) IGF-1 values also dropped: 140.4 (118.6–179.0) ng/mL versus 112.4 (99.5–143.0), p < 0.001. By contrast, the CA 125 values rose slightly but not significantly. At 6 months (n = 34), the LDH values were not significantly different from either the preoperative or the immediate postoperative values. This was observed both in patients with and without a recurrence of myoma. In contrast, the median (Q1–Q3) IGF-1 level at T2 was significantly elevated both in patients with sonographic evidence of new myomas (129.0 [116.0–163.1] ng/mL, p = 0.023) and in patients with sonographic proof of no new myomas (161.0 [130.2–198.5] ng/mL, p < 0.001). Conclusion: Both LDH and IGF-1 dropped significantly in the immediate postoperative days in women with myomas after uterus-preserving surgeries were performed. The postoperative concentration of IGF-1 was correlated with the evidence of new myomas and can be potentially used for further monitoring. Future studies should be able to confirm these results. This study concludes that myomas do influence LDH and IGF-1 and could possibly be suitable as biomarkers.

ObjectiveLow-grade serous ovarian cancers characterize a unique clinical pattern and lower chemotherapy responsiveness. The expression level of Ki67 is associated with differences in prognosis; however, this has not yet been evaluated in regard to predicting the outcome of therapy.MethodsPatients with low-grade serous ovarian cancers were identified in an institutional database. Receiver-operator characteristics (ROC) curve analysis was performed to find cut-off values of Ki67 to discriminate patients with residual tumor mass after surgery from maximal debulked patients: therapy response and therapy-free interval (TFI).ResultsA total of 68 patients with low-grade serous ovarian cancer were identified. All patients underwent surgery. 61 (89.7%) patients received platinum-based first-line chemotherapy; of these 61 patients, 13 (21.3%) had residual mass (>0 mm) after primary cytoreduction and 11 (18%) received neo-adjuvant chemotherapy. Ki67 ≥3.6% was associated with higher risk of residual mass after surgery (OR 8.1, 95% CI 1.45 to 45.18; p=0.017). Patients with Ki67 ConclusionsThis is the first study to show an association between Ki67 expression and chemotherapy response, duration of TFI to platinum-based chemotherapy as well as outcome of surgery in low-grade serous ovarian cancers. Further prospective trials should use Ki-67 as a stratification factor to explore the effect of chemotherapy and endocrine strategies.

BackgroundMaintenance therapy induces remission and prolongs disease free interval in primary and recurrent ovarian disease. For the treatment decision making process, aspects of quality of life and patients′ preferences are crucial, despite the fact that scientific data are lacking. Therefore, we conducted this European-wide study in patients with ovarian cancer.MethodsA 25 item questionnaire was provided to ovarian cancer patients via the internet or as a paper version in 10 European countries (Austria, Belgium, France, Germany, Italy, Romania, Slovenia, Finland, Turkey, and Spain). Data recorded were demographics, tumor stage, therapy after firstline and recurrent disease, preferences for administration, and expectations concerning maintenance therapy.ResultsOverall, 1954 patients participated from September 2013 to March 2016; 42% had recurrent disease. Most patients (98%) with primary epithelial ovarian cancer underwent surgery followed by chemotherapy (91%). Almost one-third of participants (29%) were receiving maintenance therapy whereas 45% had only heard of it. For 70% of patients with primary epithelial ovarian cancer, they heard about maintenance therapy from their doctor, 10% heard about maintenance therapy from other patients, and 8% from the internet. The main source of information about maintenance therapy in patients with epithelial ovarian cancer relapse was from the treating physician (72%), from other patients (8%), and from the internet (7%). For patients undergoing maintenance therapy, the four most disturbing adverse effects were polyneuropathy (37%), nausea (36%), hair loss (34%), and vomiting (34%). The main objective of maintenance treatment, as perceived by patients, was to increase the chances of cure (73%), improvement in quality of life (47%), and delay in tumor growth (37%). Many patients were willing to undergo maintenance therapy until tumor progression (38%) and 39% would prefer oral administration. No significant differences were detected in the cross country subanalysis regarding expectations of maintenance therapy and patients with primary or relapsed ovarian cancer.ConclusionPatients with ovarian cancer were willing to accept maintenance therapy of prolonged duration and preferred oral administration. There is still a gap between the efficacy of maintenance therapy and patient expectations. Patients need more information on the adverse effects and treatment goals of maintenance therapy to avoid misunderstandings.

Background/aim Involvement of lymph nodes (LNs) and their surgical resection in low-grade ovarian cancer remains a field of discussion. The aim of this study was to determine the incidence and pattern of distribution of lymph node metastases in patients with low-grade serous ovarian cancer. Patients and methods A retrospective analysis was carried out in patients with primary low-grade serous ovarian cancer who underwent primary surgery including systematic lymphadenectomy. Analysis of the affected LNs along with pattern of lymphatic spread was performed. Results Thirty-seven patients who underwent systematic pelvic and para-aortal LN dissection were identified. The median age was 48 years (range=26-76 years). The majority of patients had International Federation of Gynecology and Obstetrics stage III (89.2%). A median of 41 (range=10-97) LNs were resected. LN metastases were found in 27 (72.9%) patients. In 15 (55.5%) patients, both pelvic and para-aortic LNs were affected concomitantly, in isolated para-aortal and pelvic lymph nodes in three (11.1%) and eight (29.6%) patients, respectively. The most frequently affected region was the right obturator fossa, found in 14 (51.8%) patients, followed by the left obturator fossa in 11 (40.7%) patients. Conclusion Low-grade serous ovarian cancer exhibits a high percentage of lymphatic spread, with more confinement to the pelvic compared to the para-aortic region.

Aim of this study was to analyze the impact of pain on quality of life and survival in recurrent OC patients. Raw data including the QLQ-C30 questionnaire from three phase II/III trials (“Topotecan phase III,” “Hector,” and “TRIAS”) conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) were synthesized and analyzed using logistic and Cox regression analyses. Data on pain was available for 952 patients out of 1226. Moderate to severe pain, which was defined as pain ≥ 50 in the QLQ-C30 symptom scale, was experienced by more than one-third of patients (36.6%). A total of 31% were taking non-opioid pain medication and 16% opioids. Median age at randomization was 61 years (range 25–84). Most patients (84.7%) were diagnosed in FIGO III/IV. Pain was independent from age, FIGO stage, grading, amount of recurrences, and chemotherapy-free interval. ECOG was significantly worse in patients with pain (p

The impact of angiogenesis on long-term survival of high-grade serous ovarian cancer (HGSOC) patients remains unclear. This study investigated whether angiogenic markers correlated with 5-year progression-free survival (PFS) in a large cohort of matched advanced HGSOC tissue samples. Tumor samples from 124 primary HGSOC patients were retrospectively collected within the Tumor Bank Ovarian Cancer ( http://www.toc-network.de ). All patients were in advanced stages (FIGO stage III–IV). No patient had received anti-angiogenesis therapy. The cohort contains 62 long-term survivors and 62 controls matched by age and post-surgical tumor residuals. Long-term survivors were defined as patients with no relapse within 5 years after the end of first-line chemotherapy. Controls were patients who suffered from first relapse within 6–36 months after primary treatment. Samples were assessed for immunohistochemical expression of vascular endothelial growth factor (VEGF) A and VEGF receptor 2 (VEGFR2). Expression profiles of VEGFA and VEGFR2 were compared between the two groups. Significant correlation between VEGFA and VEGFR2 expression was observed (p

PURPOSE: To evaluate the practice patterns among centers and physicians worldwide regarding sentinel lymph node biopsies (SLNB) in cervical cancer (CC) patients. METHOD: A validated 35-item questionnaire regarding SLNB in CC supported by the Gynecologic Cancer Intergroup (GCIG), and sponsored by the North-Eastern German Society of Gynaecologic-Oncology (NOGGO) was sent to all major gynecological cancer societies across the globe for further distribution from October 2015 and continued for a period of 7 months. RESULTS: One hundred and sixty-one institutions from around the world participated. One hundred and six (66%) of the participants were from university centers and one hundred and eleven (69%) were gynecologic oncologists. One hundred and fifty-two (97%) performed lymphadenectomy (LNE), and one hundred and forty-seven (94%) did so systematically; Ninety-seven (60%) used SLNB, due to lower morbidity (73%), reliability (55%) and time-saving (27%). In cases of positive SLNB (pN+), 39% of respondents stopped the operation and sent the patient for chemoradiation (CRT), 45% completed pelvic and paraaortic LNE, whereas 26% went on to perform a radical hysterectomy (RH) and systematic pelvic and paraaortic LNE. In case of negative SLNB (pN0), 39% of institutions still performed a systematic pelvic and paraaortic LNE. CONCLUSION: In this survey worldwide SLNB adoption is an encouraging 60%, yet ample differences exist regarding strategy, and to a lower extent the techniques used. Lack of experience is the most common reason SLNB is not performed. Efforts to increase surgical education on SLNB technique and multicenter prospective trials providing evidence-based guidelines are warranted.

Malignant ascites (MA) is a frequent and common symptom in (gyneco-) oncological patients. The present trial evaluated and assessed patients’ characteristics, clinical features and the possible influence of MA on QoL measurements. A prospective observational trial was conducted from Oct 2013 until Nov 2016. Therefore an interdisciplinary questionnaire was developed. Overall 250 patients with histological confirmed MA were included with different cancer entities (gynecological, gastrointestinal). The correlation of MA caused symptoms and QoL measurements was assessed using Kendall’s tau b. Multivariable logistic regression models were applied to analyze the risks of symptoms or severe limitation in daily activities. 125 questionnaires could be analyzed. The majority of patients with MA had diagnosis of ovarian cancer (68.8%) and were under current cancer treatment (57.6%), mostly chemotherapy. Over 50% reported abdominal tension as major symptom, around 56% of the patients had MA when cancer was firstly diagnosed. Regression analysis showed that patients with MA above 2l were significantly more likely to be harmed in everyday activities. However, the age, gender, type of malignancy and the current treatment (chemotherapy vs. no chemotherapy) had no significant influence. MA has a significantly impact on QoL measurements in cancer patients and might influence everyday activities including basic needs like eating, walking and body care. There is a high need for more information and education of patients with MA

BACKGROUND/AIM Chemotherapy-associated toxicity is one of the limiting factors regarding treatment efficacy, patient outcome and quality of life in this collective. Underweight or obese patients represent a major group in which the therapy seems to be more challenging. The aim of this analysis was to evaluate the impact of BMI on the toxicity in patients undergoing chemotherapy. PATIENTS AND METHODS The data of three prospective phase II/III studies ('Tower', 'Topotecan phase III' and 'Hector') of the North-Eastern German Society of Gynecological Oncology including 1,213 patients with recurrent ovarian cancer were retrospectively analyzed. The study was performed using logistic regression and Cox regression analysis. RESULTS The median age at diagnosis was 59 years. Sixty-seven (5.5%) patients had BMI 30. Preterm termination of the chemotherapy was associated with lower BMI (p=0.017). Moreover, non-hematological toxicity grade III/IV was mainly observed in underweighted women as well (p

ObjectiveThe aim of this study was to estimate surgical outcome and survival benefit after completion surgery.MethodsWe evaluated 164 patients with epithelial ovarian cancer who underwent incomplete primary cytoreductive surgery or rather received only staging procedures from January 2000 to December 2014 in outside institutions. Patient-related data were registered in prospective database of Tumor Bank Ovarian Cancer. The outcome analyses were performed for early and advanced stages of ovarian cancer separately.ResultsThe majority of patients were at the time of completion surgery in advanced stages of disease. From overall 111 advanced epithelial ovarian cancer patients, 74 (66.6%) could be operated macroscopically tumor free, minimal residual disease 1 cm or less was achieved in 15.3% of the cases. Mean overall survival for patients without versus those with any tumor residual was 70 months (95% confidence interval, 61.3–81.5) versus 24.7 months (95% confidence interval, 7.1–42.4; P ⩽ 0.0001). After applying completion surgery, 47 (28.6%) and 12 (6.7%) patients were upstaged in FIGO (International Federation of Gynecology and Obstetrics) IIIC and IV stages, respectively. Upstaging resulted in therapy changes in 10 patients (19%) with assumed FIGO IA stages. Major operative complications were registered in 28.8% of advanced cases, and 30-day mortality reached 1.8%.ConclusionsRecent research has shown that the most profound impact on survivorship occurs when women get proper care from surgeons trained in the latest techniques for treating ovarian cancer. Completion surgery maintained that even after initial incomplete cytoreduction outside of the high specialized units, after applying appropriate surgery techniques macroscopically, disease-free situation is achievable and outcomes are comparable with the results of primary debulking surgery.

AIM This study aimed to analyze the predictive, prognostic and diagnostic value of autoantibodies to coagulation factor II thrombin receptor (F2R; protease-activated receptor 1, PAR1) (PAR1-AB) in patients with primary epithelial ovarian cancer (EOC). MATERIALS AND METHODS A total of 197 patients with primary EOC and 200 healthy female blood donors were included in the study. Enzyme-linked immunosorbent assay was applied to determine PAR1-AB levels in blood sera taken preoperatively. Correlation of PAR1-AB with clinicopathological outcome, progression-free (PFS) and overall (OS) survival was analyzed and patients were compared with controls. RESULTS PAR1-AB was significantly negatively correlated with histological grading (p=0.008) and was significantly lower in the patient group compared to healthy controls (p

Summary Background Antiangiogenic therapy has known activity in ovarian cancer. The investigator-initiated randomised phase 2 TRIAS trial assessed the multi-kinase inhibitor sorafenib combined with topotecan and continued as maintenance therapy for platinum-resistant or platinum-refractory ovarian cancer. Methods We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 trial at 20 sites in Germany. Patients (≥18 years) with platinum-resistant ovarian cancer previously treated with two or fewer chemotherapy lines for recurrent disease were stratified (first vs later relapse) in block sizes of four and randomly assigned (1:1) using a web-generated response system to topotecan (1·25 mg/m2 on days 1–5) plus either oral sorafenib 400 mg or placebo twice daily on days 6–15, repeated every 21 days for six cycles, followed by daily maintenance sorafenib or placebo for up to 1 year in patients without progression. Investigators and patients were masked to allocation of sorafenib or placebo; topotecan treatment was open label. The primary endpoint was investigator-assessed progression-free survival, analysed in all patients who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov , number NCT01047891 . Findings Between Jan 18, 2010, and Sept 19, 2013, 185 patients were enrolled, 174 of whom were randomly assigned: 85 to sorafenib and 89 to placebo. Two patients in the sorafenib group had serious adverse events before treatment and were excluded from analyses. 83 patients in the sorafenib group and 89 in the placebo group started treatment. Progression-free survival was significantly improved with sorafenib versus placebo (hazard ratio 0·60, 95% CI 0·43–0·83; p=0·0018). Median progression-free survival was 6·7 months (95% CI 5·8–7·6) with sorafenib versus 4·4 months (3·7–5·0) with placebo. The most common grade 3–4 adverse events were leucopenia (57 [69%] of 83 patients in the sorafenib group vs 47 [53%] of 89 in the placebo group), neutropenia (46 [55%] vs 48 [54%]), and thrombocytopenia (23 [28%] vs 20 [22%]). Serious adverse events occurred in 49 (59%) of 83 sorafenib-treated patients and 45 (51%) of 89 placebo-treated patients. Of these, events were fatal in four patients (5%) in the sorafenib group (dyspnoea and poor general condition, septic shock, ascites and dyspnoea, and sigma perforation) and seven (8%) in the placebo group (pulmonary embolism in two patients, disease progression in two patients, and one case each of sepsis with fever, pleural effusion, and tumour cachexia). Sorafenib was associated with increased incidences of grade 3 hand-foot skin reaction (three [13%] vs 0 patients) and grade 2 alopecia (24 [29%] vs 12 [13%]). Interpretation Sorafenib, when given orally in combination with topotecan and continued as maintenance therapy, showed a statistically and clinically significant improvement in progression-free survival in women with platinum-resistant ovarian cancer. These encouraging results support the crucial role of antiangiogenesis as the treatment backbone in combination with chemotherapy, making this approach attractive for further assessment with other targeted strategies. Funding Bayer , Amgen , and GlaxoSmithKline .

Human papillomavirus (HPV) infection is a frequent cause of malignant and non-malignant disease, in particular among persons with HIV. HPV serotype-specific anti L1 antibodies protect against HPV infection but little is known about prophylactic HPV vaccine-induced cell-mediated immunity against HPV in high-risk individuals. We recently showed that both HPV vaccines (Gardasil® and Cervarix®) induce solid, serological immune responses in HIV-infected persons. This study aimed to characterize HPV-specific CD4 T cells in HIV-infected HPV-vaccine recipients, T cell responses being critical for B cell activation and antibody-isotype switching. Thirty HIV-infected patients on long-term antiretroviral treatment (ART) received 3 doses of either Cervarix (n = 15) or Gardasil (n = 15) vaccine at month 0, 1.5 and 6. Cryopreserved peripheral blood mononuclear cells (PBMC) from baseline, 7 and 12 months were subjected to 24-hour stimulation with specific pools of HPV L1-peptides (HPV6, 11, 16, 18, 31 and 45) and HPV E6/E7-peptide pools (HPV6/11 and HPV16/18). Fluorescence-activated cell sorting with intracellular staining (IC-FACS) against CD4, CD154, IL-2, and IFNγ was performed. Frequencies (%) of HPV-antigen specific CD4+ T cells (CD154+/IL-2+ or CD154+/ IFNγ+) were determined. Both HPV-vaccines significantly and comparably enhanced cell-mediated vaccine L1 antigen-specific immunity in HIV-positive adults receiving ART therapy at month 7 and 12 after first vaccine dose. This suggests that the vaccines induce CD4 T cellular memory despite HIV-induced immune compromisation.

Ovarian cancer is usually a cancer of the older age group. Comorbidities and comedications increase with rising age. Aim of this study was to evaluate association of comorbidity and comedication with grade III/IV toxicities and prior cessation of chemotherapy in ovarian cancer patients.As an individual participant data meta-analysis this study analyzes the original data of three phase II/III chemotherapy studies of the North-Eastern German Society of Gynecological Oncology (NOGGO). Risk scores for certain combinations of risk factors were calculated based on stepwise regression analyses.Altogether, 1213 patients were included in the study. Cardiovascular disease was the most frequent comorbidity (47.5%). In multivariate analyses it was associated with hematological, non-hematological, pulmonary and renal grade III/IV toxicities (p=0.002; p0.001; p=0.005; p0.001). Renal toxicity was more frequent when using diuretics and ACE-inhibitors (p0.001; p=0.002). Prior cessation of therapy was e.g. associated with use of diuretics, insulin and digitalis (p=0.001; p=0.04; p=0.03). The risk for renal grade III/IV toxicities was more than 16 times higher when using both a diuretic and an ACE-inhibitor.Regimens of ovarian cancer treatment should not be restricted to direct cancer therapy but rather include additional individualized treatment of comorbidities. Comedications such as diuretics increase grade III/IV toxicities and patients at risk should be closely monitored.

The peritoneal cancer index (PCI) is used to refer gastrointestinal malignancy patients to either palliative or curative management of their peritoneal carcinomatosis. The aim of this retrospective study was to evaluate the prognostic value of the PCI in patients with primary advanced epithelial ovarian cancer (EOC) after complete cytoreductive surgery. PCI quantitatively assesses cancer distribution on the peritoneum by calculating tumor sizes in each of 13 abdominopelvic regions. Correlation between PCI score and clinical factors were analyzed using Kendall's tau b. Univariate and multivariate survival analyses were performed with the Kaplan–Meier method and Cox regression model, respectively. We retrospectively enrolled 80 consecutive patients with primary EOC treated in our gynecology department. All patients underwent complete cytoreductive surgery. Patients whose history included interval tumor debulking and completion cytoreductive surgery were excluded. Most tumors were of a serous histological subtype (96.3 %). Median age at diagnosis was 58.0 years. Their median PCI score was 12.0 (range 3–32). We found statistical correlations between PCI and ascites (p = 0.001), surgery duration (p

Background/aim The purpose of the study was to examine the preoperative CA-125 values as a predictive factor for postoperative outcome in primary serous ovarian cancer (POC) for complete tumor resection (CTR) and evaluate the preoperative CA-125 levels with other vital clinical dynamics such as ascites, lymph node involvement, diffuse peritoneal carcinomatosis, grading and staging. Patients and methods A cohort of 277 POC-patients aged 18-75 years, who had undergone primary cytoreductive surgery at the Department of Gynecology & Oncological Surgery, Charite, Campus Virchow Klinikum (CVK) between 2000 und 2009 was analyzed in correlation with the preoperative CA-125 values. Results The median preoperative CA-125 value in high-grade serous POC patients was 636 U/ml (204- 2312 U/ml) compared to 284 U/ml (148.5-1,378 U/ml) in low-grade serous POC patients (p=0.016). For the survival analyses both the cut-off values 252 and 475 U/ml, with highest sum from sensitivity (79.1% and 65.9%, respectively) and specificity (41.9% and 55.1%, respectively), were used to compare the relationship between preoperative CA-125 levels and (CTR), progression-free (PFS) and overall survival (OS). There was no significant difference between PFS and OS in three different groups of patients (preoperative CA-125 levels 475 U/ml). Conclusion Preoperative CA-125 is a poor, but statistically significant predictive factor for CTR after PCS. Preoperative CA-125 can predict neither the progression-free nor overall survival for POC patients.

Aim:To compare the growth attainment of preterm children and their cardiovascular risk factors at adolescence with the values measured in term children in Germany.Methods:About 17,641 children aged 0 to Results:About 11.8% of the 16,737 children with complete and valid data had been born preterm. After adjustment for covariates the estimated z-scores over the total age range were larger in term compared to preterm children for length/height (PConclusions:Preterm-born German adolescents remained significantly shorter, lighter, and had a smaller head circumference than term-born adolescents, but the risk indicators for cardiovascular diseases were not higher.

ObjectiveOvarian cancer (OC) recurrence constitutes a therapeutic dilemma with various novel targeted agents emerging that offer alternative treatment options. The aim of the present study was to evaluate and compare epithelial cell adhesion molecule (EpCAM) expression profiles in paired tumor samples of patients with OC relapse.MethodsEpCAM expression was analyzed by immunohistochemistry using the avidin-biotin-complex method on paraffin-embedded OC tissues obtained at primary surgery as well as on corresponding tumor samples of the same patients at relapse. The EpCAM overexpression was defined as 76% to 100% of tumor cells positively stained for EpCAM. Clinical data were collected within the Tumorbank Ovarian Cancer Network.ResultsNineteen patients with serous OC histology were included in the study (median age at primary diagnosis, 50 years; range, 40–74 years). The majority of the patients (95%) presented with International Federation of Gynecology and Obstetrics stage III/IV, and 68.4% of the tumors were poorly differentiated. A complete macroscopic tumor resection could be achieved in 15 patients (78.9%) at diagnosis. Epithelial cell adhesion molecule overexpression was detected in 17 (89%) of the primary and 16 (84%) of the recurrent tumors (P = 1.0); hence, no significant change of the EpCAM expression profile could be identified over time.ConclusionsEpithelial cell adhesion molecule expression profile appears to remain stable during the course from the primary throughout the relapse of serous OC. The results indicate that EpCAM might be an interesting therapeutic target structure in serous OC.

The cold shock Y-box binding protein-1 (YB-1) fulfills important roles in regulating cell proliferation and differentiation. Overexpression occurs in various tumor cells. Given the existence of extracellular YB-1 we set out to determine the diagnostic, predictive and prognostic role of serum YB-1/p18 for patients with primary epithelial ovarian cancer (EOC).The protein fragment YB-1/p18 was quantified by sandwich ELISA in serum samples from 132 healthy female volunteers and 206 patients with histological diagnosis of primary EOC. The ELISA sensitivity and specificity to detect EOC were calculated using receiver operating curves. Survival data were calculated using Kaplan Maier curves.Median age at the time of diagnosis was 60years and follow-up ended with a mean of 44.8month. 188 (91%) patients were diagnosed at advanced stages (FIGO III/IV) and 188 patients (91%) suffered from high-grade serous ovarian carcinoma. YB-1/p18 levels were significantly decreased in older patients (p=0.021). Significantly lower serum levels of YB-1/p18 were detected in the EOC cohort when compared to the control group (p0.0001, AUC=0.827; 95% CI, 0.787-0.867). Using the expression of serum YB-1/p18 in early stages I and II cases these could be differentiated from control cases (p0.0001, AUC=0.816; 95% CI 0.704-0.929). No other significant associations between clinical prognostic factors and YB-1/p18 serum levels were detected. Immunoblotting results with serum samples suggest that masking of epitopes by the YB-1/p18 fragment in multiprotein-complexes under non reducing conditions leads to the observed reduced ELISA readings in the EOC cohort.The quantification of fragment YB-1/p18 derived from cold shock protein YB-1 in serum samples could be useful for the early diagnosis of EOC.

AIM This study aimed to analyze diaphragmatic interventions and their complications in primary cytoreductive surgery (PCS) and to study their impact on attaining complete tumor resection (CTR) in advanced ovarian cancer (AOC), which is purportedly reflected in better disease-free and overall survival. PATIENTS AND METHODS The study's collective consisted of 536 consecutive patients presenting a first diagnosis of AOC who underwent PCS between 2007 and 2013 at the Charite Medical University, Berlin. A total of 268 patients underwent diaphragmatic interventions, while 268 did not undergo any kind of diaphragmatic surgery. RESULTS Diaphragmatic interventions were indicated in 50% of cases with AOC. The surgical interventions varied between diaphragmatic partial resection (44.8%), stripping (53%) and only infrared coagulation (2.2%). The postoperative complication rate was higher in the diaphragm-intervention group in comparison to the group without any diaphragmatic intervention (49.6% vs. 38.8%), but most postoperative complications were not directly related to the diaphragmatic intervention itself but to the statically significant increase of other radical surgical procedures in this group. Pleura effusion was the only increased complication with a direct correlation with diaphragmatic surgery (25.4% vs. 14.2%). Preoperatively apparent stage IV (pleura effusion) disease, very high cancer antigen-125 value, serous papillary tumors and the presence of massive ascites (>500 ml) were statistically significant predictors of the need for diaphragmatic surgery in order to achieve CTR. CONCLUSION Our current findings consider diaphragmatic surgery as being acceptable, feasible and in many cases as an essential intervention to achieve CTR or suboptimal debulking with an acceptable complication rate.

The combination of carboplatin and topotecan in platinum-sensitive relapsed ovarian cancer could not improve progression-free survival or overall survival compared with established standard regimens. Background Randomized, phase III trial to evaluate safety and efficacy of topotecan and carboplatin (TC) compared with standard platinum-based combinations in platinum-sensitive recurrent ovarian cancer (ROC). Patients and methods Patients were randomly assigned in a 1:1 ratio to the experimental TC arm (topotecan 0.75 mg/m2/ days 1–3 and carboplatin AUC 5 on day 3 every 3 weeks) or to one of the standard regimes [(PC) paclitaxel plus carboplatin; (GC) gemcitabine plus carboplatin; (PLDC) pegylated liposomal doxorubicin and carboplatin] which could be chosen by individual preference but before randomization. The primary end point was progression-free survival (PFS) after 12 months. Overall survival (OS), response rate, toxicity, quality of life and treatment preference regarding standard treatment were defined as secondary end points. Results A total of 550 patients were recruited. The PFS rate after 12 months was 37.0% for TC compared with 40.2% in the standard combinations (P = 0.470). The overall response rate was 73.1% for TC versus 75.1% for standard combinations (P = 0.149). After a median follow-up of 20 months, the median PFS was 10 months [95% confidence interval (CI) 9.4–10.6] and did not differ between both arms (P = 0.414). The median OS was 25 months in the TC arm versus 31 months in the standard arm (95% CI: 22.4–27.6 resp. 26.0–36.0; P = 0.163). Severe hematologic toxicities (grade 3/4) were rare in the experimental arm (P Conclusion The combination of carboplatin and topotecan was well tolerated with significant lower rates of severe hematological toxicities but did not improve PFS or OS in platinum-sensitive relapsed ovarian cancer compared with established standard regimens.

To gather standardized information of current perioperative management of gynecological oncology patients and to evaluate up to what extent the Enhanced Recovery after Surgery (ERAS) elements are established in the clinical routine of gynecologic oncology units in Germany.We performed a multi-centric nationwide survey among 654 primary, secondary and maximal health care gynecological departments in Germany. A multiple-choice questionnaire based on the principles of ERAS was developed to gather information about perioperative management of two fictional cases in gynecological oncology.One hundred four units (22%) have been taken the survey. Only 49.5% of surveyed hospitals claimed to be adherent to more than 70% of ERAS elements in managing perioperative period of primary cytoreductive surgery in ovarian cancer patients. 21% of these hospitals implemented more than 80% and only 8.4% implemented more than 90%. The results in border-line tumors operations did not differ from those of ovarian cancer operations.The implementation of ERAS elements in gynecologic oncology in Germany is still not satisfying as only half of the departments will now be able to apply 70% of these principles. Therefore, we plan the second step of this survey in order to be able to build a consistent structured reporting platform between gynecological oncology units in Germany to facilitate the wide implementation and standardization of ERAS protocol.

We aimed to identify the surgical-pathological risk factors separately for pelvic and para-aortic lymph nodes (LN) metastases in endometrial cancer (EC).The study cohort consisted of 179 patients with first diagnosis of EC, who were operated in our Institution between 2007 and 2014.Pelvic and para-aortic LN dissection was performed in 115 patients (64.2%). The positive pelvic and para-aortic LN were diagnosed in 11.3% and 16.1% of cases, respectively. Patients with bad differentiated tumors (G3) showed about 5-times more risk to have affected LN. Deep infiltration of myometrium elevated the risk of pelvic LN infiltration 5 times and of para-aortic LN infiltration 14 times. G3, myometrial infiltration50% and type II endometrial cancer correlated with a worse progression free survival (PFS) and overall survival (OS).Tumor grade and deep myometrial invasion were the only significant predictors of pelvic and para-aortic lymph node metastases.

Germline mutations in BRCA1 gene have been reported in up to 20 % of epithelial ovarian cancer (EOC) patients. Distinct clinical characteristics have been attributed to this special EOC population. We hypothesized that mutations in different BRCA1 gene exons may differently affect the clinical course of the disease. The aim of this study was to analyze, in a large cohort of primary EOCs, the clinical impact of mutations in BRCA1 gene exon 11, the largest exon of the gene sequence encoding the 60 % of BRCA1 protein. Two hundred sixty-three primary EOC patients, treated between 2000 and 2008 at Charite University Hospital of Berlin, were included. Patients’ blood samples were obtained from the Tumor Ovarian Cancer (TOC) Network ( www.toc-network.de ). Direct sequencing of BRCA1 gene exon 11 was performed for each patient to detect mutations. Based on their BRCA1 exon 11 mutational status, patients were compared regarding clinico-pathological variables and survival. Mutations in BRCA1 exon 11 were found in 18 out of 263 patients (6.8 %). Further 10/263 (3.8 %) cases showed variants of uncertain significance (VUS). All exon 11 BRCA1-positive tumors (100 %) were Type 2 ovarian carcinomas (p = 0.05). Age at diagnosis was significantly younger in Type 2 exon 11 mutated patients (p = 0.01). On multivariate analysis, BRCA1 exon 11 mutational status was not found to be an independent predictive factor for optimal cytoreduction, platinum response, or survival. Mutations in BRCA1 gene exon 11 seem to predispose women to exclusively develop a Type 2 ovarian cancer at younger age. Exon 11 BRCA1-mutated EOC patients showed distinct clinico-pathological features but similar clinical outcome with respect to sporadic EOC patients.

Neuroendocrine neoplasms (NEN) of the female genital tract account for 2% of gynecological cancers. The aim of this study was to share our experience of 11 primary neuroendocrine neoplasms of the ovary.All patients who presented and/or were treated at our Institution with histologically-confirmed NEN of the ovary were included. Clinical data including tumor stage, diagnostic and therapeutic management and survival were assessed. Pathological specimens were critically reviewed.We identified 11 patients with NEN of the ovary consisting of nine neuroendocrine cancers and two carcinoids. Median age was 55.9 years. NEN were mostly poorly differentiated (72.4%). Primary surgery was performed in all patients. Adjuvant chemotherapy was administered in five patients consisting of platinum-based regimens. Median overall survival was 20 months.We propose a diagnostic algorithm for NEN of the ovary and discuss possible treatments according to FIGO stages. Patients should be included in multicenter studies whenever possible.

Background: To assess the clinical impact of the two histological types as designated in the proposed model for ovarian tumourigenesis in primary epithelial ovarian, fallopian tube or peritoneal cancer (EOC) patients. Methods: All consecutive EOC patients (n=632) after primary tumour debulking in our institution (09/2000–08/2010) were classified into one of two groups: type I tumours (n=100; 15.8%) composed of low-grade serous, low-grade endometrioid, clear cell, mucinous and transitional carcinomas; and Type II tumours (n=532; 84.1%) composed of high-grade serous, high-grade endometrioid, undifferentiated and malignant mixed-mesodermal tumours. Kaplan–Meier and logistic/Cox-regression analyses were performed to assess the impact of histological type on surgical outcome and survival. Results: Type II patients had a significantly higher incidence of advanced disease (FIGO III/IV) than Type I patients (79.8% vs 38%, respectively; P