Despite advances in surgical techniques and chemotherapy, ovarian cancer is still a leading cause of death among gynecological cancers. In addition to the late detection of the disease, the main reason for poor prognosis is resistance to pharmacotherapy, mostly platinum compounds. About a third of patients do not respond to primary platinum-based chemotherapy treatment, and over time, eventually, 80% of other patients develop chemoresistance, which makes the recurrence of disease incurable. In this review, we describe a difficult clinical hurdle faced in ovarian cancer therapy as a result of platinum resistance, as well as resistance to newer targeted therapy with PARP inhibitors and bevacizumab. We, furthermore, give attention also to the role of the tumor microenvironment as it is less well understood than the tumor cell-intrinsic mechanism. Because a central goal in ovarian cancer research is the development of novel strategies to overcome chemoresistance, treatment for cancer is moving toward personalized therapy.

In parallel to medical treatment of ovarian cancer, methods for the early detection of cancer tumors are being sought. In this contribution, the use of non-invasive static (SLS) and dynamic light scattering (DLS) for the characterization of extracellular nanoparticles (ENPs) in body fluids of advanced serous ovarian cancer (OC) and benign gynecological pathology (BP) patients is demonstrated and critically evaluated. Samples of plasma and ascites (OC patients) or plasma, peritoneal fluid, and peritoneal washing (BP patients) were analyzed. The hydrodynamic radius (R_h) and the radius of gyration (R_g) of ENPs were calculated from the angular dependency of LS intensity for two ENP subpopulations. R_h and R_g of the predominant ENP population of OC patients were in the range 20–30 nm (diameter 40–60 nm). In thawed samples, larger particles (R_h mostly above 100 nm) were detected as well. The shape parameter ρ of both particle populations was around 1, which is typical for spherical particles with mass concentrated on the rim, as in vesicles. The R_h and R_g of ENPs in BP patients were larger than in OC patients, with ρ ≈ 1.1–2, implying a more elongated/distorted shape. These results show that SLS and DLS are promising methods for the analysis of morphological features of ENPs and have the potential to discriminate between OC and BP patients. However, further development of the methodology is required.

Background: Osteopontin (sOPN) is a promising blood tumour marker for detecting epithelial ovarian cancer (EOC). However, other clinical uses of sOPN as a tumour marker in EOC are still lacking. Since sOPN concentrations in serum are not associated with those in ascites, we compared clinical value of sOPN concentrations in the two body fluids. Patients and methods: The study included 31 women with advanced EOC and 34 women with benign gynaecological pathology. In the EOC group, serum for sOPN analysis was obtained preoperatively, after primary debulking surgery and after chemotherapy. In the control group, serum was obtained before and after surgery. Ascites and peritoneal fluid were obtained during surgery. sOPN concentrations were determined by flow cytometry bead-based assay. Results: The sensitivity and specificity of sOPN in detecting EOC was 91.2% and 90.3% (cut-off = 47.4 ng/ml) in serum, and 96.8% and 100% (cut-off = 529.5 ng/ml) in ascites. Kaplan-Meier analysis showed a significant association between higher serum sOPN concentration and overall survival ( p = 0.018) or progression free survival ( p = 0.008). Higher ascites sOPN concentrations were associated with suboptimally debulked tumour and unresectable disease. Higher serum sOPN concentrations were associated with refractory disease or incomplete response to platinum-based chemotherapy. Conclusions: The study showed that ascites sOPN level mirrors present disease and is superior to serum level for diagnostic purposes and surgical planning, although the end result of treatment is the response of the whole body in fighting the disease. The preoperative sOPN concentration in serum thus better reflects disease outcome.

Late rupture of external iliac artery pseudo-aneurysm is an uncommon complication in patients who undergo extensive gynecologic radical surgeries. A 28-year-old woman with stage IB cervical cancer underwent pelvic lymphadenectomy and extrafascial trachelectomy. Two months after surgery, massive bleeding from ruptured pseudo-aneurysm of the external iliac artery occurred. Endovascular management with covered stent placement was feasible and safe to stop bleeding.

Sertoli - Leydig cell tumors (SLCTs) are sex-cord stromal tumors that account less than 0.5 % of primary ovarian neoplasms. They are mostly benign and occur in reproductive age women. Variants with heterologous mesenchymal elements are exceptionaly rare. The usual presentation of SLCTs is with signs of androgen excess as majority of them produce androgens. We present a case of a SLCT occurring in a 70 year old woman. Her presenting complaint was abdominal distension and pain. She had no signs of androgen or estrogen excess. Transvaginal ultrasound (TVUS) and CT scan showed a multilocular adnexal tumor and level of CA 125 was raised. A complete cytoreduction was achieved with surgical procedure. Histopathological examination revealed moderately differentiated SLCT with retiform areas and owergrowth of heterologous component in form of embrional rhabdomyosarcoma (RMS). She returned 7 months after the surgery with a large abdominal mass, ascites, right- sided hydronephrosis and massive pulmonary embolism. Due to the widespread disease and her poor general condition, she received only palliative care. She died 15 days after the admission. No autopsy was performed. Due to the rarity of SLCTs, especially those with retiform areas and heterologous elements, their management remains challenging. There is no firm evidence that adjuvant chemotherapy is effective in improving survival in SLCTs with malignant heterologous elements. Further studies with a higher number of cases and a longer follow-up are needed to better predicting the prognosis and determine the role of chemotherapy in such cases.

Background: Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods: We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results: Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions: Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery.