When and how should peritoneal endometriosis be operated on in order to improve fertility rates and symptoms? The experience and outcomes of nearly 100 cases

Purpose: To analyze the follow-up results of patients suffering from symptomatic early-stage endometriosis after a consistent laparoscopic peritoneal stripping of the altered peritoneum (peritoneal endometriosis and surrounding inflamed tissue) was performed. This type of endometriosis is resistant to medical therapy and/or impairs fertility. Methods: Using our prospectively maintained database, we were able to identify all symptomatic women with the suspicion of only peritoneal endometriosis who underwent laparoscopy at our endometriosis center over a period of 5 years. All procedures were carried out in a standardized fashion by one single surgeon, who is highly experienced in minimal invasive surgery, and included a suspended hormonal pretreatment for 2 months. Postoperative outcomes including complications, fertility and recurrence rates were analysed. Results: Laparoscopic peritonectomy was performed on 94 women. Follow-up data were available in 87% of these cases. At the time of surgery, almost all patients tested showed signs of stage I or II endometriosis (44.7 and 48.9%, respectively). More than three-quarters of the women reported pain relief, inter alia, due to the post-surgical hormonal therapy. About one-third of the patients wanted to have children after the procedure. 62% of them became pregnant and the majority did so without the need for assisted reproductive therapy. In seven women a re-operation was performed. Conclusion: According to our data, a consistent excision of altered peritoneum followed by adjuvant hormonal therapy and multimodal concepts results in better outcomes for the patient, particularly in regards to pregnancy and recurrence rates

Dynamics of the intratumoral immune response during progression of high-grade serous ovarian cancer

PURPOSE: Tumor-infiltrating lymphocytes (TILs) have an established impact on the prognosis of high-grade serous ovarian carcinoma (HGSOC), however, their role in recurrent ovarian cancer is largely unknown. We therefore systematically investigated TIL densities and MHC class I and II (MHC1, 2) expression in the progression of HGSOC. EXPERIMENTAL DESIGN: CD3+, CD4+, CD8+ TILs and MHC1, 2 expression were evaluated by immunohistochemistry on tissue microarrays in 113 paired primary and recurrent HGSOC. TILs were quantified by image analysis. All patients had been included to the EU-funded OCTIPS FP7 project. RESULTS: CD3+, CD4+, CD8+ TILs and MHC1 and MHC2 expression showed significant correlations between primary and recurrent tumor levels (Spearman rho 0.427, 0.533, 0.361, 0.456, 0.526 respectively; P<.0001 each). Paired testing revealed higher CD4+ densities and MHC1 expression in recurrent tumors (Wilcoxon P=.034 and P=.018). There was also a shift towards higher CD3+ TILs levels in recurrent carcinomas when analyzing platinum-sensitive tumors only (Wilcoxon P=.026) and in pairs with recurrent tumor tissue from first relapse only (Wilcoxon P=.031). High MHC2 expression was the only parameter to be significantly linked to prolonged progression-free survival after first relapse (PFS2, log-rank P=.012). CONCLUSIONS: This is the first study that analyzed the development of TILs density and MHC expression in paired primary and recurrent HGSOC. The level of the antitumoral immune response in recurrent tumors was clearly dependent on the one in the primary tumor. Our data contribute to the understanding of temporal heterogeneity of HGSOC immune microenvironment and have implications for selection of samples for biomarker testing in the setting of immune-targeting therapeutics

Impact of brief prewarming on anesthesia-related core-temperature drop, hemodynamics, microperfusion and postoperative ventilation in cytoreductive surgery of ovarian cancer: a randomized trial

Background: General (GA)- and epidural-anesthesia may cause a drop in body-core-temperature (BCT(drop)), and hypothermia, which may alter tissue oxygenation (StO(2)) and microperfusion after cytoreductive surgery for ovarian cancer. Cell metabolism of subcutaneous fat- or skeletal muscle cells, measured in microdialysis, may be affected. We hypothesized that forced-air prewarming during epidural catheter placement and induction of GA maintains normothermia and improves microperfusion. Methods: After ethics approval 47 women scheduled for cytoreductive surgery were prospectively enrolled. Women in the study group were treated with a prewarming of 43 °C during epidural catheter placement. BCT (Spot on®, 3 M) was measured before (T(1)), after induction of GA (T(2)) at 15 min (T(3)) after start of surgery, and until 2 h after ICU admission (T(ICU2h)). Primary endpoint was BCT(drop) between T(1) and T(2). Microperfusion-, hemodynamic- and clinical outcomes were defined as secondary outcomes. Statistical analysis used the Mann-Whitney-U- and non-parametric-longitudinal tests. Results: BCT(drop) was 0.35 °C with prewarming and 0.9 °C without prewarming (p < 0.005) and BCT remained higher over the observation period (ΔT(4) = 0.9 °C up to ΔT(7) = 0.95 °C, p < 0.001). No significant differences in hemodynamic parameters, transfusion, arterial lactate and dCO(2) were measured. In microdialysis the ethanol ratio was temporarily, but not significantly, reduced after prewarming. Lactate, glucose and glycerol after PW tended to be more constant over the entire period. Postoperatively, six women without prewarming, but none after prewarming were mechanical ventilated (p < 0.001). Conclusion: Prewarming at 43 °C reduces the BCT(drop) and maintains normothermia without impeding the perioperative routine patient flow. Microdialysis indicate better preserved parameters of microperfusion. Trial registration: ClinicalTrials.gov; ID: NCT02364219; Date of registration: 18-febr-2015

Biological Impact of Unilateral Oophorectomy. Does the Number of Ovaries Really Matter? [Biologische auswirkungen der einseitigen ovarektomie: Kommt es wirklich auf die anzahl der eierstöcke an?]

Although unilateral oophorectomies are performed more often than bilateral ones in women of reproductive age, their clinical consequences have been less intensively investigated. Experimental models in animals have shown that compensa- tory mechanisms occur after a unilateral oophorectomy (UO). This review aims to summarize the available evidence on the biological effects of unilateral oophorectomy on wom- en. Evaluated outcomes include age at onset of menopause, risk of cardiovascular and neurological disease, risk of mortal- ity and fertility outcome after spontaneous conception or in vitro fertilization (IVF). Results were compared with findings reported after bilateral oophorectomy and/or ovarian excision and/or women with intact ovaries. An electronic database search was performed using PubMed and Scopus, followed by a manual search to identify controlled studies that com- pared women after UO with women with two intact ovaries. In particular, a systematic review of fertility outcomes after IVF was performed, and the data were summarized in a table. Women who underwent UO had a similar age at menopause and similar clinical pregnancy rate compared to women with two ovaries. However, decreased ovarian reserve affecting the quantity but not the quality of the ovarian pool after IVF was observed in the UO group. Furthermore, an increased risk of neurological disease and even an increased risk of mortality was observed in women with single ovary. These data need to be confirmed by further studies, and a plausible mecha- nism of action must be identified. At present, patients who undergo UO can be reassured with regard to their reproduc- tive potential and their age at onset of menopause

The systemic treatment of recurrent ovarian cancer revisited

Treatment approaches for relapsed ovarian cancer have evolved over the past decade from a calendar-based decision tree to a patient-oriented biologically driven algorithm. Nowadays, platinum-based chemotherapy should be offered to all patients with a reasonable chance of responding to this therapy. The treatment-free interval for platinum is only one of many factors affecting patients' eligibility for platinum re-treatment. Bevacizumab increases the response to chemotherapy irrespective of the cytotoxic regimen and can be valuable in patients with an urgent need for symptom relief (e.g. pleural effusion, ascites). For patients with recurrent high-grade ovarian cancer, which responds to platinum-based treatment, maintenance therapy with a poly(ADP-ribose) polymerase inhibitor can be offered, regardless of the BRCA mutation status. Here we review contemporary decision-making processes in the systemic treatment of relapsed ovarian cancer

Management of malignant dysgerminoma of the ovary

The evolution of treatment for malignant ovarian germ cell tumors has been one of the most successful in the history of gynecologic oncology, with dysgerminoma as the most common type of malignant ovarian germ cell tumors. Since the introduction of platinum-based chemotherapy in the 1980s, 5-year survival rates for early-stage dysgerminomas have been close to 100%, and as high as 98% for advanced stages. Despite this remarkable achievement, many questions remain in routine treatment. By performing a literature review, we aim to highlight both the current treatment of malignant dysgerminoma and unanswered questions in the modern management of this disease. These issues relate firstly to surgical therapy, such as the role of routine omentectomy and lymphadenectomy, the value of complete surgical resection, and the possibility of fertility-sparing surgery. Second, chemotherapy and the question of the possibility of de-escalation in early stages and the potential of neoadjuvant chemotherapy in advanced stages will be addressed. Finally, a brief overview of the current developments of new drug treatment regimens will be given

preoperative c reactive protein and thrombocyte count as potential markers for longterm survival in ovarian cancer

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Maintenance therapy of patients with recurrent epithelial ovarian carcinoma with the anti-tumor-associated-mucin-1 antibody gatipotuzumab: results from a double-blind, placebo-controlled, randomized, phase II study

BACKGROUND: Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced epitope of the tumor-associated mucin-1 (TA-MUC1). This study aimed to evaluate the efficacy and safety of switch maintenance therapy with gatipotuzumab in patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer. PATIENTS AND METHODS: In this double-blind, randomized, placebo-controlled, phase II trial, patients with at least stable disease (SD) following chemotherapy were randomized 2:1 to receive intravenous gatipotuzumab (500 mg followed by 1700 mg 1 week later) or placebo every 3 weeks until tumor progression or unacceptable toxicity occurred. Stratification factors were the number of prior chemotherapy lines (2 versus 3-5), response versus SD after the most recent chemotherapy, and progression-free survival (PFS) <6 versus 6-12 months following the prior therapy. Primary endpoint was PFS according to modified immune-related RECIST 1.1 response criteria. Secondary endpoints were PFS at 6 months, safety, overall response rate, CA-125 progression, overall survival, quality of life, and pharmacokinetics. RESULTS: Overall, 216 patients were randomized to gatipotuzumab (n  =  151) or placebo (n  =  65). Median PFS with gatipotuzumab was 3.5 months as compared with 3.5 months with placebo (hazard ratio 0.96, 95% confidence interval 0.69-1.33, P  =  0.80). No advantage for gatipotuzumab over placebo was seen in the secondary efficacy endpoints or in any stratified subgroups. Gatipotuzumab was well tolerated, with mild to moderate infusion-related reactions being the most common adverse events. CONCLUSIONS: Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients. TRIAL REGISTRATION: ClinicalTrials.govNCT01899599; https://clinicaltrials.gov/ct2/show/NCT01899599

Clinical management of borderline tumours of the ovary: results of a multicentre survey of 323 clinics in Germany

The aim of this survey was to analyse the standard of care in diagnostic, surgery, chemotherapy and aftercare management for patients with borderline tumours of the ovary (BOTs) in Germany. A structured questionnaire comprising different dimensions was sent to all 1114 gynaecological departments. The questionnaire could be returned anonymously. The overall response rate was 29.0% (323 departments). Most departments were on secondary care (71.8%), tertiary care (23.2%) or university hospital (5.0%) level. Most clinicians performed not more than five BOT operations (89.2%) per year. Most departments (93.2%) used in addition to classical bimanual examination and vaginal ultrasound, tumour marker CA-125 detection, CT scan, MRI or PET-CT techniques. Departments in university and tertiary care hospitals performed more often a fresh frozen section (87 vs 64%). In young women, clinicians performed much seldom unilateral salpingo-oophorectomy (92%) and only in 53% biopsies of the contralateral ovary. Generally, biopsies of the contralateral ovary were performed in 4–53% of the patients. Chemotherapy was mostly favoured in ‘high-risk' patients with tumour residual, microinvasion or invasive implants. Thus, a high grade of insecurity in diagnostic and therapy of BOT exists in some gynaecological departments and underlines the need for more educational and study activities