Current Treatments and New Possible Complementary Therapies for Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is one of the deadliest gynaecological malignancies. The late diagnosis is frequent due to the absence of specific symptomatology and the molecular complexity of the disease, which includes a high angiogenesis potential. The first-line treatment is based on optimal debulking surgery following chemotherapy with platinum/gemcitabine and taxane compounds. During the last years, anti-angiogenic therapy and poly adenosine diphosphate-ribose polymerases (PARP)-inhibitors were introduced in therapeutic schemes. Several studies have shown that these drugs increase the progression-free survival and overall survival of patients with ovarian cancer, but the identification of patients who have the greatest benefits is still under investigation. In the present review, we discuss about the molecular characteristics of the disease, the recent evidence of approved treatments and the new possible complementary approaches, focusing on drug repurposing, non-coding RNAs, and nanomedicine as a new method for drug delivery.

Immunotherapy in Ovarian Cancer: Thinking Beyond PD-1/PD-L1

Ovarian cancer (OC) is the most lethal gynecologic malignancy, affecting approximately 1 in 70 women with only 45% surviving 5 years after diagnosis. This disease typically presents at an advanced stage, and optimal debulking with platinum-based chemotherapy remains the cornerstone of management. Although most ovarian cancer patients will respond effectively to current management, 70% of them will eventually develop recurrence and novel therapeutic strategies are needed. There is a rationale for immune-oncological treatments (IO) in the managements of patients with OC. Many OC tumors demonstrate tumor infiltrating lymphocytes (TILs) and the degree of TIL infiltration is strongly and reproducibly correlated with survival. Unfortunately, results to date have been disappointing in relapsed OC. Trials have reported very modest single activity with various antibodies targeting PD-1 or PD-L1 resulting in response rate ranging from 4% to 15%. This may be due to the highly immunosuppressive TME of the disease, a low tumor mutational burden and low PD-L1 expression. There is an urgent need to improve our understanding of the immune microenvironment in OC in order to develop effective therapies. This review will discuss immune subpopulations in OC microenvironment, current immunotherapy modalities targeting these immune subsets and data from clinical trials testing IO treatments in OC and its combination with other therapeutic agents.

Behaviour and Prognosis of Ovarian Cancer With Rare Metastatic Sites

Purpose: Ovarian cancer is the commonest gynecologic malignancy in Egypt. Although metastasis from ovarian cancer is common, there are still sites with rarely reported deposits as non-regional nodes, bone, and brain. Methods: This is a chorort study were we retrospectively a group of patients over 7 years period recruited from the data system of a cancer centre. All the recruited patients suffered a rare distant metastasis from ovarian cancer. Results: Nearly half of the patients already had metastasis at the time of the initial presentation, while the rest developed during the disease course. Debulking was feasible in nearly half of the patients with long overall and progression-free survival. Tumours with non-regional nodal metastases tend to have excellent survival. Conclusion: we recommend offering these patients optimal debulking and considering those with a non-regional nodal spread as having a curable disease.

Total Colectomy as a Part of Ultra-Radical Surgery for Ovarian Cancer—Short- and Long-Term Outcomes

(1) Background: The aim of this study was to assess the outcomes for patients who underwent total colectomy (TC) as a part of surgery for ovarian cancer (OC). (2) Methods: We performed a retrospective analysis of 1636 OC patients. Residual disease (RD) was reported using Sugarbaker’s completeness of cytoreduction score. (3) Results: Forty-two patients underwent TC during primary debulking surgery (PDS), and four and ten patients underwent TC during the interval debulking surgery (IDS) and secondary cytoreduction, respectively. The median overall survival (mOS) in OC patients following the PDS was 45.1 months in those with CC-0 (21%) resection, 11.1 months in those with CC-1 (45%) resection and 20.0 months in those with CC-2 (33%) resection (p = 0.28). Severe adverse events were reported in 18 patients (43%). In the IDS group, two patients survived more than 2 years after IDS and one patient died after 28.6 months. In the recurrent OC group, the mOS was 6.9 months. Patient age above 65 years was associated with a shortened overall survival (OS) and the presence of adverse events. (4) Conclusions: TC as a part of ultra-radical surgery for advanced OC results in high rates of optimal debulking. However, survival benefits were observed only in patients with no macroscopic disease.

Gene Co-Expression Network Analysis Confirms Four Independent Predictors of Survival In Ovarian Cancer Patients Under Optimal Debulking Surgery

Background: Serious ovarian cancer (OvCa) is the most common histological type of epithelial OvCa with poor prognosis. Despite received optimal cytoreduction and standard chemotherapy, a large proportion of patients are forced to recurrence or death within three years. To identify exact prognostic biomarkers associated with overall survival (OS) is urgent requirements of exploring rapid tumor progression mechanisms and developing novel strategies for immunotherapy.Methods: The gene expression profiles of GSE49997, GSE9891 and TCGA were screened through rigorous criteria using R software and Bioconductor package. Weighted gene co-expression network analysis (WGCNA) was constructed to figure out gene clusters associated with OS. Protein-protein interaction (PPI) networks were built through STRING website. Prognostic values of potential biomarkers were validated using forest map and Kaplan-Meier analysis.Results: According to screening criteria, 788 samples and 10402 genes were reserved as the modeling dataset. We detected five modules related to OS and intersected 108 genes through WGCNA after random sampling. PPI network analysis, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed potential mechanisms of above biomarkers. Conclusions: Four exact biomarkers (CANT1, P4HB, DUS1L and SIRT7) were confirmed as independent predictors of survival in OvCa patients with success of debulking surgery, which might provide promising biomarkers for prognostic judgement in ovarian cancer.

The Role of Ultra-Radical Surgery in the Management of Advanced Ovarian Cancer: State or Art

The ovarian cancer, also known as “silent killer”, has remained the most lethal gynaecological malignancy. The single independent risk factor linked with improved survival is maximum cytoreductive effort resulting in no macroscopic residual disease. This could be gained through ultra-radical surgery which demands tackling significant tumour burden in pelvis, lower and upper abdomen which usually constitutes bowel resection, liver mobilisation, ancillary cholecystectomy, extensive peritonectomy, diaphragmatic resection, splenectomy, resection of enlarged pelvic, paraaortic, and rarely cardio-phrenic lymph nodes in order to achieve optimal debulking. The above can be achieved through a holistic approach to patient’s care, meticulous patient selection, and full engagement of the family. The decision needs to be carefully balanced after obtaining an informed consent, and an appreciation of the impact of such surgery on the quality of life against the survival benefit. This chapter will describe the complexity and surgical challenges in the management of advanced ovarian cancer.

Difficulty in Diagnosing Peritoneal Fluid Cytology in Ovarian Yolk Sac Tumor Cases

Objective : This article objective is to describe cytology diagnosis difficulties of yolk sac tumors of the ovary.Method : Case reports and literature review.Case : The author reports the case of a 24 year old woman who complained of an enlarged stomach. Serum AFP increased to 16,519.7 U/mL. Ultrasound examination revealed solid and irregular mass of ovarian, so the conclusion was suspect ovarian carcinoma. Conclusion of CT scan examination was a solid ovarian tumor. The working diagnosis was suspect ovarian carcinoma. Optimal debulking was performed, accompanied by taking a sample from the peritoneal rinse fluid. Microscopic examination of peritoneal fluid showed the distribution and group of cells with pleomorphic nuclei, partly hyperchromatic, partly vesicular with coarse chromatin and prominent nucleoli. There were also cells with polygonal nuclei, small nuclei, basophilic and vacuole cytoplasm with a mucoid background. These cells formed a solid arrangement. Conclusion from these features was carcinoma metastases to the peritoneal fluid. Microscopic examination from tumor tissue sample showed an ovarian yolk sac tumor appearance.Conclusion : Cytologic examination of peritoneal fluid in cases of ovarian yolk sac tumor is quite difficult to determine the diagnosis. This is due to the microscopic appearance of tumor cells which often looks like a carcinoma and limited literature about this tumors in the peritoneal fluid.Keywords: Yolk sac tumor, ovary,

Ovarian Clear Cell Carcinoma which Detected in Ascitic Fluid Smear

Objective: To report the case of ovarian clear cell carcinoma with involvement of both ovaries and metastatic to ascitic fluid and the label mass in the bladderMethod: Case Report Case: A 51 years old female presented with enlarging abdominal with gradual pain. The result of transabdominal sonography were multiple cysts with solid mass, suspected solid cystic ovarian neoplasm and ascites. The patient prepared for laparotomy; optimal debulking surgery, mass resection from bladder. Cytology examination was performed from ascitic fluid and it was confirmed by histopathology examination.Result: Microscopic features on cytology examination of ascitic fluid smear was suggest carcinoma. Histological examination was confirmed the diagnosis and the result was ovarian clear cell carcinoma. Discussion: Ovarian clear cell carcinoma is a rare subtype of epithelial ovarian cancer and comprises about 5-10% of ovarian carcinomas. Clear cell carcinoma tends to occur in the fifth to seventh decades. Cytology examination showed the cellular smear consists of groups of epithelial cells with large nucleus, hyperchromatic, pale-staining, vacuolated cytoplasm. There is also eosinophilic, extracellular substance. The presence of a tumor in ascitic fluid and the label mass in the bladder can categorize become IIB. This determined based on the FIGO’s ovarian tumor staging system.Keywords: ovarian clear cell carcinoma; ascitic fluid.