Patients' perspectives towards malignant ascites: results of a prospective observational trial regarding expectations, characteristics and quality of life-a study of the North-Eastern-German Society of Gynecological Oncology.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prognostic impact of neuroendocrine differentiation in high-grade serous ovarian carcinoma.

Neuroendocrine differentiation in high-grade serous ovarian carcinomas has only rarely been described. However, in our consultancy experience, we have been pointed at a case of neuroendocrine relapse in a patient with high-grade serous ovarian carcinoma where retrospectively, a minor neuroendocrine component in the primary tumor could be detected. Hypothesizing that immunohistochemical evidence of neuroendocrine differentiation might be more frequent in ovarian carcinoma than suspected by morphology, we immunophenotyped the tissue microarrays (TMAs) of a cohort of 178 high-grade serous carcinomas for chromogranin and synaptophysin expression. Synaptophysin expression was found in 12 (6.7 %) out of 172 patients, and chromogranin A expression was seen in 36 (20.7 %) out of 174 patients. Kaplan-Meier analysis revealed that carcinomas with synaptophysin expression of >20 % of positive cells (n = 4) had a significantly shorter survival time than those with 0-20 % of positive cells (p < 0.0001). Synaptophysin expression remained a significant prognostic factor in multivariate analysis (HR = 10.82, 95 % confidence interval 3.10-37.71, p < 0.0001), independently of age, FIGO stage, and residual tumor after surgery. A trend toward shorter survival was seen in patients with tumors that expressed chromogranin, irrespective of the amount of positive cells (p = 0.173). A neuroendocrine differentiation is important to keep in mind when a neuroendocrine tumor of unknown primary is detected in regional or temporal connection with an ovarian carcinoma. A minor neuroendocrine component in ovarian high-grade serous carcinomas might imply a dismal prognosis.

Prognostic role of early versus late onset of bone metastasis in patients with carcinoma of the ovary, peritoneum and fallopian tube.

BACKGROUND: Bone metastases are a rare manifestation in the management of ovarian cancer and thought to be associated with a poor prognosis as sign of distant spread. Only few data exist on this rare condition. The present study aimed to more information on this very distinct patient collective. PATIENTS AND METHODS: A retrospective chart review was carried out including all patients who had been treated from 1994 to 2009 for histologically confirmed ovarian, peritoneal and fallopian tube cancer. Overall, 1717 cases were detected and screened. Patients with bone metastasis were identified and analyzed regarding survival as well as various clinical variables. RESULTS: A total of 26 women who had been diagnosed with bone metastases ante mortem could be identified, resulting in an incidence of 1.50%. The majority of patients presented multiple bone lesions (80.8%) and bone spread was symptomatic in 62.5% of the cases. Mean overall survival from primary diagnosis of EOC was 50.5 months (range: 2.5-142.5 months). Median overall survival after diagnosis of bone metastases was 7.2 months. When divided into two subsets depending on timepoint diagnosis of bone metastases, there was a significant difference in overall survival. The mean overall survival from primary diagnosis of EOC in the early-onset group (n = 8), defined as occurence of bone manifestation within 12 months, was 11.2 months. The mean overall survival in the late-onset group (n = 15) was 78.4 months (P = 0.000001). CONCLUSIONS: The time interval from diagnosis to appearance of bone metastases is a prognostic factor in ovarian cancer. While early onset bone spread has a strong negative prognostic impact, late-onset bone diagnosis of bone metastases hardly influences the prognosis at all. This finding should be considered in the management of patients with bone metastases from ovarian cancer.

Quaternary cytoreductive surgery in ovarian cancer: does surgical effort still matter?

BACKGROUND: To evaluate surgical outcome and survival benefit after quaternary cytoreduction (QC) in epithelial ovarian cancer (EOC) relapse. METHODS: We systematically evaluated all consecutive patients undergoing QC in our institution over a 12-year period (October 2000-January 2012). All relevant surgical and clinical outcome parameters were systematically assessed. RESULTS: Forty-nine EOC patients (median age: 57; range: 28-76) underwent QC; in a median of 16 months (range:2-142) after previous chemotherapy. The majority of the patients had an initial FIGO stage III (67.3%), peritoneal carcinomatosis (77.6%) and no ascites (67.3%). At QC, patients presented following tumour pattern: lower abdomen 85.7%; middle abdomen 79.6% and upper abdomen 42.9%. Median duration of surgery was 292 min (range: a total macroscopic tumour clearance could be achieved. Rates of major operative morbidity and 30-day mortality were 28.6% and 2%, respectively.Mean follow-up from QC was 18.41 months (95% confidence interval (CI):12.64-24.18) and mean overall survival (OS) 23.05 months (95% CI: 15.5-30.6). Mean OS for patients without vs any tumour residuals was 43 months (95% CI: 26.4-59.5) vs 13.4 months (95% CI: 7.42-19.4); P=0.001. Mean OS for patients who received postoperative chemotherapy (n=18; 36.7%) vs those who did not was 40.5 months (95% CI: 27.4-53.6) vs 12.03 months (95% CI: 5.9-18.18); P<0.001.Multivariate analysis indentified multifocal tumour dissemination to be of predictive significance for incomplete tumour resection, higher operative morbidity and lower survival, while systemic chemotherapy subsequent to QC had a protective significant impact on OS. No prognostic impact had ascites, platinum resistance, high grading and advanced age. CONCLUSION: Even in this highly advanced setting of the third EOC relapse, maximal therapeutic effort combining optimal surgery and chemotherapy appear to significantly prolong survival in a selected patients 'group'.

Clinical experience of young patients with small cell ovarian carcinoma of the hypercalcemic type (OSCCHT).

OBJECTIVE: Small cell ovarian cancer of the hypercalcemic type (OSCCHT) is a very rare and highly aggressive disease which mainly affects young women, while optimal treatment guidelines have not yet been defined. The objective of this work is to present our experience with four OSCCHT patients. STUDY DESIGN: We evaluated the surgical course and clinical outcome of all OSCCHT patients treated in the European Competence Center for Ovarian Cancer, Charité, University Medicine of Berlin. Pathology was reviewed by specialized gynecological pathologists of our center. RESULTS: Four OSCCHT patients were identified between 2008 and 2011 (median age: 24.5 years; range: 18-29) out of 845 ovarian cancer patients being operated on within this timeframe. Two patients were diagnosed at a very early tumor stage (FIGO Ia), one in FIGO IIb, and one patient presented with advanced stage disease FIGO IIIc. Treatment of choice was surgery followed by adjuvant platinum-based chemotherapy. In all patients the uterus was preserved and also the contralateral ovary in three out of the four patients. Within a median follow-up time of 22 months (range: 8-47) only the FIGO IIIC-patient relapsed twice and died 15 months after initial diagnosis. The other three patients are all alive and with no signs of relapse at 8, 29 and 47 months after initial diagnosis. CONCLUSION: OSCCHT is a rare tumor entity which usually affects young women with hopes of childbearing. The clinical course varies widely and although it is associated with an overall dismal prognosis, fertility-sparing surgery followed by platinum-based adjuvant chemotherapy may be considered in early stages of the disease.

Extraperitoneal response to intraperitoneal immunotherapy with catumaxomab in a patient with cutaneous lymphangiosis carcinomatosa from ovarian cancer: a case report and review of the literature.

Cutaneous metastasation is a very rare manifestation of ovarian cancer. We present the case of a 64-year-old woman with recurrent platinum-refractory ovarian cancer and skin metastasis. The patient was treated with intraperitoneal catumaxomab due to massive refractory malignant ascites. Clinical response of the skin metastasis was observed during the intraperitoneal treatment with catumaxomab. Even though response of extraperitoneal tumor sites can be explained with intravascular uptake and a possible vaccination effect, this phenomenon has not been reported up to this point to the best of our knowledge.

Feasibility of surgery after systemic treatment with the humanized recombinant antibody bevacizumab in heavily pretreated patients with advanced epithelial ovarian cancer.

BACKGROUND: The aim of this study was to assess operative feasibility and outcome after bevacizumab treatment (BT) in ovarian cancer (OC) patients. PATIENTS AND METHODS: We retrospectively identified all OC patients operated between April 2006 and September 2010 after BT. RESULTS: We identified 733 OC operations, 10 of which (1.36%) were performed in a mean time of 134 days (range, 10-288) after BT. Indication was secondary cytoreduction in 3 patients (mean days after BT, 181; range, 82-256) and palliation in 7 due to bowel obstruction and/or intestinal perforation or fistula (mean days after BT, 114; range, 10-288). All but 1 acutely operated patients developed a secondary wound healing, but none of the 3 patients after planned cytoreduction did. Of these 3 patients, 1 suddenly died on the 36th postoperative day, presumably of thromboembolism. None of the patients developed postoperatively a gastrointestinal morbidity; however, in 1 patient operated 21 days after BT due to a vesicointestinal fistula the bladder reconstruction could not heal and developed a permanent fistula. CONCLUSIONS: Emergency surgery after BT due to bowel obstruction and/or fistulas seems to be associated with an impaired wound healing in advanced heavily pretreated platinum-resistant OC patients, while this does not appear the case in planned cytoreduction. Prospective evaluations are warranted to assess surgical safety after BT in this special patients' collective.

The Prescription of the Morning-After Pill in a Berlin Emergency Department Over a Four-Year Period - User Profiles and Reasons for Use.

Questions: There are no current health care studies from Germany regarding the "morning-after pill". This paper will use routine data to analyse details regarding the users' profiles, reasons for using it and the utilisation of hospital outpatient facilities. Patient Collective and Methods: Retrospective analysis of all triage sheets in the emergency department of the Virchow Hospital Campus/Charité University Hospital, Berlin, over a four-year period from 2007 to 2010 that were coded with the ICD diagnosis Z30 (= contraception advice) and statistical processing of the associated administrative data. Results: 860 triage sheets were included in the analysis. The emergency department is used most frequently for the prescription of the "morning-after pill" at the weekend. The average age of the users was 25.1 years. The most common reason cited for needing emergency contraception was unprotected sexual intercourse, with the second-most common being "condom failure". Around half of the women attended the department within 12 hours of having unprotected sex. Less than 2 % (n = 14) of all women decided against a prescription of emergency contraceptive after counselling. Conclusions: The user profile and reasons for using emergency oral contraception correlate largely with the information contained in international literature. Although the "morning-after pill" is probably prescribed mainly in general practices in Germany, and despite the availability of new drugs with a permitted post-exposure interval of up to 120 hours after unprotected sex, there appears to still be a high demand for counselling and prescriptions of the "morning-after pill" in the context of the emergency department.

Role of histological type on surgical outcome and survival following radical primary tumour debulking of epithelial ovarian, fallopian tube and peritoneal cancers.

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<0.001). Median CA125 values (438 vs 93 U ml(-1); P=0.001); operative time (258 vs 237 min; P=0.001); and incidence of incomplete tumour resection (34.4% vs 15%; P<0.001) were significantly higher in patients with Type II. During a mean follow-up time of 23 months (range: 1-106), 17% of patients with type I vs 34.8% of patients with type II tumours relapsed and/or died (P<0.001). Overall survival (P=0.021) and progression-free survival (P=0.003) were also significantly higher in patients with type I tumours. Multivariate analysis, while identifying postoperative tumour residuals, positive lymph nodes and extrapelvic dissemination as independent predictors of survival, failed to demonstrate any prognostic significance of histological type. CONCLUSION: Type I EOC patients appear to present at earlier stages have significantly higher survival and more optimal surgical outcome compared with type II patients. However, in advanced stages, histology loses significance as an independent prognosticator.

Optimizing the clinical management of gynecological and breast cancer via online tumor conferences.

BACKGROUND: The therapy of gynecological malignancies and breast cancer requires a multimodal therapy approach based on current individualized and risk adapted state of the art therapy concepts. The aim of this online tumor conference project is to reach a broad interdisciplinary and cross-sectoral participation of specialists in order to develop high-quality therapy recommendations for complex casuistics. PATIENTS AND METHODS: The concept of the interdisciplinary online tumor conference was established in 2004 at the Department of Gynecology, Charité Campus Virchow, University Hospital of Berlin to conduct online tumor board meetings of specialists in the field of gynecological cancer from different hospitals and gynecological and oncological practitioners from the outpatient sector. Following a systematic approach, patient data, relevant external clinical evidence and therapy preference are presented to the participants. An individual therapy recommendation for each patient is reached by consensus discussion. RESULTS: By July 2009, 131 online tumor conferences had been performed with a total of 275 participants were developed. Per session, a median of 14 participants logged in online. Additionally 398 second opinion recommendations were performed. In an anonymous survey, carried out at the beginning of 2009, 95% of the participating physicians reported being satisfied with the information content and 50% were stimulated to seek more second opinions by the possibility of the online tumor conference. All contributors attested to a high comprehension of the developed therapy recommendations; 70% confirmed further that the conference presents an optimal possibility for fast and detailed exchange of information between disciplines and care sectors (in- and out-patient) and improves advanced educational training (81%). CONCLUSION: The online tumor conference provides a time saving and high quality possibility for receiving a treatment recommendation based on the best available clinical and scientific evidence and contributes to continuously advanced training for therapists in the field of gynecological cancer.

Cervical manifestation of a borderline type ovarian cancer with pseudomyxoma peritonei - a case report.

Borderline tumours of the ovary (BOTs) are rare tumour entities that do not show any destructive or invasive growth in the majority of cases, even though they can display characteristics of malignant tumours The mucinous subtype can also originate from the appendix, and ovarian metastases can mimic primary ovarian BOTs, often accompanied by peritoneal manifestation in terms of pseudomyxoma peritonei. In cases where a concomitant appendiceal tumour is present, it may prove difficult to determine the primary tumour. This report describes a special case of BOT with a specific example of the complexity of the differential diagnosis of pseudomyxoma peritonei. Especially the case was simultaneously linked to appendiceal and ovarian cancer. Moreover, this case was exceptional for its unusual manifestation of BOT in the cervix.

Prognostic role of platinum sensitivity in patients with brain metastases from ovarian cancer: results of a German multicenter study.

BACKGROUND: Ovarian cancer is the leading cause of death in women with gynecological malignancies. Brain metastases are considered an uncommon metastatic site. Only few data exist on prognostic factors for this patient collective. PATIENTS AND METHODS: A multicenter retrospective chart review was carried out including all patients with histologically confirmed ovarian cancer from six different German hospitals from 1981 to 2008. Overall, 4277 cases of patients with ovarian cancer were screened and patients with brain metastasis were identified and analyzed regarding various clinical variables and survival. RESULTS: A total of 74 women with brain metastases were identified, resulting in an incidence of 1.73%. In multivariate analysis, the following clinical parameters had a significant impact on overall survival: multiple lesions [hazard ratio (HR) 4.4, 95% confidence interval (CI) 2.0-9.7] and low grading (HR 3.1, 95% CI 1.7-5.8) were associated with a negative impact. Platinum sensitivity (HR 0.23, 95% CI 0.12-0.48) was significantly associated with a favorable outcome. Good performance status (60%-80% HR 0.48, 95% CI 0.23-0.99 and 90%-100% HR 0.21, 95% CI 0.08-0.53) also had a positive impact on overall survival. CONCLUSIONS: Platinum sensitivity is the most important prognostic factor in patients with ovarian cancer metastatic to the brain. This novel finding should be considered in the strategy of multimodal therapy for brain metastases in ovarian cancer.