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Objective: This study aims to evaluate the effect of the COVID-19 pandemic and related restrictions on patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer., Methods: We retrospectively evaluated ovarian cancer patients who underwent HIPEC following complete cytoreductive surgery performed during the outbreak of the COVID-19 pandemic in three different centers specializing in gynecological oncology. All patients who underwent cytoreduction plus HIPEC for a primary, interval, and recurrent surgery were evaluated. Primary outcomes was postoperative 30-day morbidity and mortality. The secondary outcome was infection of patient and/or related staff with COVID-19 during the perioperative or early postoperative period., Results: We performed a total of 35 HIPEC procedures during the pandemic: 15 (42.9%) patients underwent primary/interval surgery, while 20 (57.1%) patients had recurrent disease. Grade 3-4 complications occurred in one patient (2.9%) (chronic renal failure), while mortality did not occur in any patient. Neither the patients nor related staff were infected with the coronavirus during the perioperative or early postoperative period. One patient, who was diagnosed with COVID-19 pneumonia on postoperative day 80 died from the infection. Another patient died on postoperative day 85 due to progressive ovarian cancer, a disorder in vital functions, and organ failure., Conclusion: HIPEC during the COVID-19 pandemic seems a safe and feasible procedure, with acceptable morbidity and mortality rates. Careful selection of patients is important and precautions should be taken before the procedure., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: The aim of this study was to analyze the factors affecting recurrence-free (RFS) and overall survival (OS) rates of women diagnosed with low-grade serous ovarian cancer (LGSOC)., Methods: Databases from 13 participating centers in Turkey were searched retrospectively for women who had been treated for stage I-IV LGSOC between 1997 and 2018., Results: Overall 191 eligible women were included. The median age at diagnosis was 49 years (range, 21-84 years). One hundred seventy-five (92%) patients underwent primary cytoreductive surgery. Complete and optimal cytoreduction was achieved in 148 (77.5%) and 33 (17.3%) patients, respectively. The median follow-up period was 44 months (range, 2-208 months). Multivariate analysis showed the presence of endometriosis (p = .012), lymphovascular space invasion (LVSI) (p = .022), any residual disease (p = .023), and the International Federation of Gynecology and Obstetrics (FIGO) stage II-IV disease (p = .045) were negatively correlated with RFS while the only presence of residual disease (p = .002) and FIGO stage II-IV disease (p = .003) significantly decreased OS., Conclusions: The maximal surgical effort is warranted for complete cytoreduction as achieving no residual disease is the single most important variable affecting the survival of patients with LGSOC. The prognostic role of LVSI and endometriosis should be evaluated by further studies as both of these parameters significantly affected RFS., (© 2021 Wiley Periodicals LLC.)

Ovarian cancer remains one of the most frequent causes of cancer-related death in women. Many patients with ovarian cancer suffer from de novo or acquired resistance to chemotherapy. Here, we report that RAB25 suppresses chemotherapy-induced mitochondrial apoptosis signaling in ovarian cancer cell lines and primary ovarian cancer cells. RAB25 blocks chemotherapy-induced apoptosis upstream of mitochondrial outer membrane permeabilization by either increasing antiapoptotic BCL-2 proteins or decreasing proapoptotic BCL-2 proteins. In particular, BAX expression negatively correlates with RAB25 expression in ovarian cancer cells. BH3 profiling assays corroborated that RAB25 decreases mitochondrial cell death priming. Suppressing RAB25 by means of RNAi or RFP14 inhibitory hydrocarbon-stapled peptide sensitizes ovarian cancer cells to chemotherapy as well as RAB25-mediated proliferation, invasion and migration. Our data suggest that RAB25 is a potential therapeutic target for ovarian cancer.

Purpose: Ovarian cancer is the fifth leading cause of cancer related death in women. Platin-based doublet regimens plus bevacizumab is standard treatment in relapse. Due to formal regulation of Turkish Ministry of Health, adjuvant bevacizumab has not been reimbursed and clinicians can use bevacizumab at a dose of 7.5 mg/kg/3wk in platin-resistant and sensitive relapse settings. The primary aim of this study was to evaluate 7.5 mg/kg/3wk bevacizumab dosing in platin-resistant and sensitive relapse ovarian cancer and compare these findings with the current literature., Methods: A total of 106 patients with relapsed ovarian cancer and treated with bevacizumab (bevacizumab is not reimbursed as a part of adjuvant treatment in Turkey) on their first relapse were included., Results: At a median follow-up of 32.1 months (5.3-110.8), 56 (52.8%) patients died. Progression-free survival (PFS) and overall survival (OS) were estimated at 18.8 months (14.4-23.3) vs 29.7 months (24.3-35.1) of the whole group overall survival. We observed that 78.4% of patients treated with primary surgery without neoadjuvant treatment and 59 (57.8%) out of the 102 patients with debulking surgery relapsed. A significant number of patients (81%) treated with primary surgery without neoadjuvant treatment and 59 (76.6 %) had secondary debulking surgery at relapse. In relapse, 38 patients were treated with single agent liposomal doxorubicin (LPD) plus bevacizumab. On the other hand, 68 patients were treated with carboplatin and LPD plus bevacizumab. Multivariate analysis failed to show any clinicopathological characteristics with significant effect on PFS. However, cytoreductive surgery at relapse showed significant effect on OS. Bevacizumab-related toxicities were detected in 23 (21.7%) patients; hypertension, pulmonary embolism, perforation, and other toxicities (nephrotic syndrome in 2, osteonecrosis in 2, cerebrovascular and cardiac ischemia in 3 patients) were seen in 12 (11.3%), 3 (2.8%), 1 (0.9%) and 7 (6.6%) patients, respectively., Conclusions: In conclusion, our findings showed that 7.5 mg/kg/3week dosing of bevacizumab in relapsed ovarian cancer could have similar effectiveness compared to standard 15 mg/kg/3week dosing. Increase of OS and PFS in patients treated with primary and secondary debulking surgery with no-visible disease was more pronounced. No new safety information was observed but lower rate of grade 3 or above hypertension with similar rate of severe vascular and intestinal complications were detected.

Objective: To identify factors predictive of poor prognosis in women with stage III nonserous epithelial ovarian cancer (EOC) who had undergone maximal or optimal primary cytoreductive surgery (CRS) followed by six cycles of intravenous carboplatin/paclitaxel chemotherapy., Methods: A multicenter, retrospective department database review was performed to identify patients with stage III nonserous EOC who had undergone maximal or optimal primary CRS followed by six cycles of carboplatin/paclitaxel chemotherapy at seven gynecological oncology centers in Turkey. Demographic, clinicopathological and survival data were collected., Results: A total of 218 women met the inclusion criteria. Of these, 64 (29.4%) patients had endometrioid, 61 (28%) had mucinous, 54 (24.8%) had clear-cell and 39 (17.9%) had mixed epithelial tumors. Fifty-five (25.2%) patients underwent maximal CRS, whereas 163 (74.8%) had optimal debulking. With a median follow-up of 31.5 months, the 5-year progression-free survival (PFS) and overall survival (OS) rates were 34.8% and 44.2%, respectively. Bilaterality (hazard ratio [HR] 1.44, 95% CI 1.01-2.056; P = 0.04), age (HR 2.25, 95% CI 1.176-4.323; P = 0.014) and maximal cytoreduction (HR 0.34, 95% CI 0.202-0.58; P < 0.001) were found to be independent prognostic factors for PFS. However, age (HR 2.6, 95% CI 1.215-5.591; P = 0.014) and maximal cytoreduction (HR 0.31, 95% CI 0.166-0.615; P < 0.001) were defined as independent prognostic factors for OS., Conclusion: The extent of CRS seems to be the only modifiable prognostic factor associated with stage III nonserous EOC. Complete cytoreduction to no gross residual disease should be the main goal of management in these women., (© 2018 Japan Society of Obstetrics and Gynecology.)

Background: The purpose of this study was to compare the prognoses of women with pure ovarian clear cell carcinoma (OCCC) arising from endometriosis to those of women with pure OCCC not arising from endometriosis treated in the same manner., Methods: A dual-institutional, retrospective database review was performed to identify patients with pure OCCC who were treated with maximal or optimal cytoreductive surgery (CRS) followed by paclitaxel/carboplatin chemotherapy between January 2006 and December 2016. Patients were divided into two groups according to the detection of cancer arising in endometriosis or not, on the basis of pathological findings. Demographic, clinicopathological, and survival data were collected, and prognosis was compared between the two groups., Results: Ninety-three women who met the inclusion criteria were included. Of these patients, 48 (51.6%) were diagnosed with OCCC arising in endometriosis, while 45 (48.4%) had no concomitant endometriosis. OCCC arising in endometriosis was found more frequently in younger women and had a higher incidence of early stage disease when compared to OCCC patients without endometriosis. The 5-year overall survival (OS) rate of the patients with OCCC arising in endometriosis was found to be significantly longer than that of women who had OCCC without endometriosis (74.1 vs. 46.4%; p = 0.003). Although univariate analysis revealed the absence of endometriosis (p = 0.003) as a prognostic factor for decreased OS, the extent of CRS was identified as an independent prognostic factor for both recurrence-free survival (hazard ratio (HR) 8.7, 95% confidence interval (CI) 3.15-24.38; p < 0.001) and OS (HR 11.7, 95% CI 3.68-33.71; p < 0.001) on multivariate analysis., Conclusion: Our results suggest that endometriosis per se does not seem to affect the prognosis of pure OCCC.

Objective: The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in patients with stage III ovarian high-grade serous carcinoma (HGSC)., Methods: A multicenter, retrospective department database review was performed to identify patients with ovarian HGSC at 6 gynecologic oncology centers in Turkey. A total of 229 node-positive women with stage III ovarian HGSC who had undergone maximal or optimal cytoreductive surgery plus systematic lymphadenectomy followed by paclitaxel plus carboplatin combination chemotherapy were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 3 groups: LNR1 (<10%), LNR2 (10%≤LNR<50%), and LNR3 (≥50%). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models., Results: Thirty-one women (13.6%) were classified as stage IIIA1, 15 (6.6%) as stage IIIB, and 183 (79.9%) as stage IIIC. The median age at diagnosis was 56 (range, 18-87), and the median duration of follow-up was 36 months (range, 1-120 months). For the entire cohort, the 5-year overall survival (OS) was 52.8%. An increased LNR was associated with a decrease in 5-year OS from 65.1% for LNR1, 42.5% for LNR2, and 25.6% for LNR3, respectively (p<0.001). In multivariate analysis, women with LNR≥0.50 were 2.7 times more likely to die of their tumors (hazard ratio [HR]=2.7; 95% confidence interval [CI]=1.42-5.18; p<0.001)., Conclusion: LNR seems to be an independent prognostic factor for decreased OS in stage III ovarian HGSC patients., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology)

Objective: The objectives of this study were to examine demographic and clinicopathologic characteristics and to determine the effects of primary surgery, surgical staging and the extensiveness of staging., Methods: In a retrospective Turkish multicenter study, 539 patients, from 14 institutions, with borderline ovarian tumors were investigated. Some of the demographic, clinical and surgical characteristics of the cases were evaluated. The effects of type of surgery, surgical staging; complete or incomplete staging on survival rates were calculated by using Kaplan-Meier method., Results: The median age at diagnosis was 40 years (range 15-84) and 71.1% of patients were premenopausal. The most common histologic types were serous and mucinous. Majority of the staged cases were in Stage IA (73.5%). 242 patients underwent conservative surgery. Recurrence rates were significantly higher in conservative surgery group (8.3% vs. 3%). Of all patients in this study, 294 (54.5%) have undergone surgical staging procedures. Of the patients who underwent surgical staging, 228 (77.6%) had comprehensive staging including lymphadenectomy. Appendectomy was performed on 204 (37.8%) of the patients. The median follow-up time was 36 months (range 1-120 months). Five-year survival rate was 100% and median survival time was 120 months. Surgical staging, lymph node sampling or dissection and appendectomy didn't cause any difference on survival., Conclusion: Comprehensive surgical staging, lymph node sampling or dissection and appendectomy are not beneficial in borderline ovarian tumors surgical management., (© 2013.)

Objective: To investigate ghrelin and obestatin expression in serous ovarian tumours., Materials and Methods: Preparations of deparaffinized blocks obtained from the pathology archives of a total of 47 previously diagnosed cases of benign serous tumour (n = 20), borderline serous tumour (n = 7) and malignant serous tumour (n = 20) were subjected to immunohistochemical examination to find out ghrelin and obestatin expressions., Results: Mean ghrelin expressions decreased significantly in the benign group, relative to the malignant group (p < 0.05), while there was no significant change in mean obestatin expression. It was established that rates of preparations with moderate and severe ghrelin and obestatin expression displayed a significant increase from benign to malignant ones (p < 0.05)., Conclusion: The fact that rates of preparations with severe expression correlated with an increase in malignancy suggests that ghrelin and obestatin may be effective in the malignant transformation in at least some cases.

Ovulation-inducing drugs have been widely used for various types of infertility since the beginning of 1960s and their use increases day by day parallel to the success achieved in fertility treatment. However, the researches performed in the last two decades have begun to discuss about the safety of these drugs and the risks associated with their use. Especially, the potential neoplastic effects of these drugs are increasingly questioned. The studies have discussed whether there is an association between the exposure to ovulation-inducing drugs and the incidence of various cancers. Moreover, several studies have been performed to reveal whether there is an increased risk of childhood cancers in children conceived after fertility treatment. The point we reached through the available data is that the risk of breast, uterine and invasive ovarian cancers is not increased, but the risk of borderline ovarian tumors might increase after such a therapy. The risk of cancer has been found similar for children conceived after fertility treatment and those conceived naturally. It should also be kept in mind that cancers are overdiagnosed in infertile women population because of the close medical surveillance, which may also contribute to the early detection of cancers. Although it is still early to state the last words on this topic, the possible association should be addressed when obtaining an informed consent before starting treatment.