IMPORTANCE Ovarian cancer has the highest mortality rate among gynecologic malignant tumors. Data are lacking on the survival benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with ovarian cancer who underwent primary or interval cytoreductive surgery.OBJECTIVE To assess the clinical benefit of HIPEC after primary or interval maximal cytoreductive surgery in women with stage III or IV primary advanced ovarian cancer. DESIGN, SETTING, AND PARTICIPANTSIn this single-blind randomized clinical trial performed at 2 institutions in South Korea from March 2, 2010, to January 22, 2016, a total of 184 patients with stage III or IV ovarian cancer with residual tumor size less than 1 cm were randomized (1:1) to a HIPEC (41.5 °C, 75 mg/m 2 of cisplatin, 90 minutes) or control group. The primary end point was progression-free survival. Overall survival and adverse events were key secondary end points. The date of the last follow-up was January 10, 2020, and the data were locked on February 17, 2020. EXPOSURES Hyperthermic intraperitoneal chemotherapy after cytoreductive surgery.MAIN OUTCOMES AND MEASURES Progression-free and overall survival. RESULTSOf the 184 Korean women who underwent randomization, 92 were randomized to the HIPEC group (median age, 52.0 years; IQR, 46.0-59.5 years) and 92 to the control group (median age, 53.5 years; IQR, 47.5-61.0 years). After a median follow-up of 69.4 months (IQR, 54.4-86.3 months), median progression-free survival was 18.8 months (IQR, 13.0-43.2 months) in the control group and 19.8 months (IQR, 13.7-55.4 months) in the HIPEC group (P = .43), and median overall survival was 61.3 months (IQR, 34.3 months to not reported) in the control group and 69.5 months (IQR, 45.6 months to not reported) in the HIPEC group (P = .52). In the subgroup of interval cytoreductive surgery after neoadjuvant chemotherapy, the median progression-free survival was 15.4 months (IQR, 10.6-21.1 months) in the control group and 17.4 months (IQR, in the HIPEC group (hazard ratio for disease progression or death, 0.60; 95% CI, 0.37-0.99; P = .04), and the median overall survival was 48.2 months (IQR, 33.8-61.3 months) in the control group and 61.8 months (IQR, 46.7 months to not reported) in the HIPEC group (hazard ratio, 0.53; 95% CI, 0.29-0.96; P = .04). In the subgroup of primary cytoreductive surgery, median progression-free survival was 29.7 (IQR, 17.2-90.1 months) in the control group and 23.9 months (IQR, 12.3-71.5 months) in the HIPEC group, and the median overall survival was not reached in the control group and 71.3 months (IQR, 45.6 months to not reported) in the HIPEC group. CONCLUSIONS AND RELEVANCEThe addition of HIPEC to cytoreductive surgery did not improve progression-free and overall survival in patients with advanced epithelial ovarian cancer. Although the results are from a subgroup analysis, the addition of HIPEC to interval cytoreductive surgery provided an improvement of progression-free and overall survival.

Objective: The aim of the present study was to determine the prognostic significances of markers of preoperative systemic inflammatory response (SIR) in patients with ovarian clear cell carcinoma (OCCC).Methods: A total of 109 patients diagnosed with OCCC that underwent primary cytoreductive surgery and adjuvant platinum-based chemotherapy from 2009 to 2012 were enrolled in this retrospective study. SIR markers were calculated from complete blood cell counts determined before surgery. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). Prognostic significances with respect to overall survival (OS) and progression-free survival (PFS) were determined by Kaplan-Meier curve and multivariate Cox regression analysis.Results: The optimized NLR, LMR and PLR cut-off values as determined by ROC curve analysis for PFS and OS were 2.3, 4.2, and 123.6, respectively. When the cohort was divided using these optimized cut-offs, NLR and LMR were found to be significantly associated with clinicopathologic factors, NLR with FIGO stage, the presence of malignant ascites, and platinum response, and LMR with FIGO stage, lymph node metastasis, malignant ascites, and platinum response. Kaplan-Meier analysis revealed a high NLR (> 2.3) was significantly associated with low 5-year PFS and OS rates and that a high LMR was significantly associated with high 5-year PFS and OS rates. Multivariate analysis identified FIGO stage, residual mass, and platinum response as independent prognostic factors of PFS, and FIGO stage, residual mass, platinum response, and LMR as independent prognostic factors of OS.Conclusions: Markers of systemic inflammatory response provide useful prognostic information and lymphocyte-to-monocyte ratio is the most reliable independent prognostic factor of overall survival in patients with ovarian clear cell carcinoma.

Background: Myocardial fibrosis is a common pathophysiological change in cardiovascular disease, which can cause cardiac dysfunction and even sudden death. Excessively activated fibroblasts proliferate and secret excessive extracellular matrix (ECM) components, resulting in normal cardiac structural damage and cardiac fibrosis. We previously found that human endothelial progenitor cell (EPC)-derived exosomes, after hypoxia/reoxygenation (H/R) induction, could significantly increase the mesenchymal-endothelial transition (MEndoT) compared to normal culture EPC-derived exosomes. Exosomes have been shown to carry different nucleic acids, including microRNAs. However, the effects of microRNAs in EPC-derived exosomes on MEndoT and myocardial fibrosis remain unknown. Methods: EPCs were isolated from human peripheral blood, and fibroblasts were isolated from rat hearts, then transfected with miR-133 inhibitor, si-YBX-1, and ov-YBX-1 into EPCs. After H/R induction for 48 h, isolation and characterization of exosomes derived from human EPCs were performed. Finally, fibroblasts were treated by exosome at 48 h. The expression of miR-133 was measured by qRT-PCR; YBX-1 expression was measured by qRT-PCR and western blot. Angiopoiesis was measured by tube formation assay. Endothelial markers and fibrosis markers were measured by western blot. Results: H/R treatment promoted miR-133 expression in EPCs and EPC-derived exosomes. miR-133 could be incorporated into exosomes and transmitted to cardiac fibroblasts, increasing the angiogenesis and MEndoT of cardiac fibroblasts. miR-133 silencing in H/R-induced EPCs could inhibit miR-133 expression in EPCs and EPCsderived exosomes. miR-133 silencing in H/R-induced EPCs could inhibit the angiogenesis and MEndoT of cardiac fibroblasts and reverse the effect of H/R treatment. Additionally, miR-133 was specially sorted into H/R-induced EPCderived exosomes via YBX-1. YBX-1 silencing inhibited miR-133 transfer and reduced fibroblast angiogenesis and MEndoT. Conclusion: miR-133 was specially sorted into H/R-induced EPC-derived exosomes via YBX-1 to increase fibroblast angiogenesis and MEndoT.

The objective of this review is to discuss the common surgical strategy of cytoreductive surgery after neoadjuvant chemotherapy, with an emphasis on incorporating extensive cytoreductive surgery to remove traces of regressed tumor. A review of the literature regarding cytoreductive surgery after neoadjuvant chemotherapy and cancer stem cells is given together with the authors’ own experience and comments. Most ovarian cancer cells consist of transformed cells that regress after neoadjuvant chemotherapy. Therefore, the extent of cytoreductive surgery usually tends to be limited because only visible tumors are removed. Scar tissue, which represents tumor after neoadjuvant chemotherapy, may contain cancer stem cells. This leads to chemotherapy-resistant cancer stem cells to persist in patients who have received neoadjuvant chemotherapy. If the extent of cytoreductive surgery is preserved based on initial images, and includes all scar tissue suggestive of previously existing ovarian cancer in patients who underwent interval debulking surgery after neoadjuvant chemotherapy, treatment outcome will be improved or be comparable to patients who underwent primary cytoreductive surgery with minimal morbidity. Further basic and clinical investigation is needed to serve as a standard surgical paradigm in the management of advanced ovarian cancer. Currently, the gynecologic oncologist should remove all traces of regressed tumor after neoadjuvant chemotherapy to eradicate potential cancer stem cells. Further investigation to clarify the role of cancer stem cell in the surgical management of ovarian cancer is warranted.

Human papillomavirus (HPV) DNA is considered as a hallmark of cervical cancer. We investigated whether persistent HPV DNA at the cervix is associated with local recurrence after radiotherapy in patients with locally advanced cervical cancer. A total of 156 patients with HPV-positive cervical cancer (International Federation of Gynecology and Obstetrics stage IB-IVB) treated with radiotherapy between July 2003 and December 2006 were analyzed. HPV DNA was measured prior to radiotherapy and after completion of radiotherapy. The results of HPV DNA test at postradiotherapy 1, 3, 6 and 12 months were analyzed individually for association with local recurrence-free survival (LRFS). In addition, the result of any last follow-up HPV test within 24 months postradiotherapy was defined as the overall status of HPV at 24 months and was also analyzed for association with LRFS. HPV DNA was cleared in 127 patients (81.4%) and persistent in 29 patients (18.6%) by 24 months. In 18 patients with local recurrences, 14 patients (78%) showed positive HPV tests at 1-3 months. Among the various time points analyzed, a positive HPV test at 3 months was the most accurate predictor of local recurrence. Multivariate analysis indicated that overall status of HPV at 24 months, low HPV viral load and histologic grade as being significantly related to poor LRFS. In HPV-positive cervical carcinoma treated primarily with radiotherapy, persistent HPV DNA within 24 months after treatment indicates a high risk of local recurrence. Diagnostic accuracy of HPV test was highest at 3 months.Cervical cancer is a significant health problem worldwide, ranking second highest in cancer incidence and fourth highest in site-specific cause of cancer death in women.1,2 While concurrent chemoradiotherapy is the main treatment modality for locally advanced cervical cancer, treatment failure in the central pelvis occurs in approximately 20-25% of patients. 3,4 Cytological tests are commonly inaccurate in detecting locally persistent or recurrent disease because the effect of radiation on the cells may result in ambiguous cell morphology in the early postradiotherapy period.5 Because positive high-risk human papillomavirus (HPV) DNA is considered as an important tool in the diagnosis of both preinvasive and invasive cervical cancer, the usefulness of the HPV test has often also been considered as a method of post-treatment surveillance. Previous studies have examined the effectiveness of the HPV DNA test as a clinically useful marker for detecting residual disease or recurrence after conservative surgical procedures for cervical intraepithelial neoplasia 6-8 and also after radiotherapy. [9][10][11][12] In terms of radiotherapy outcome, several past studies showed that HPV persistence is associated with high rates of local recurrence and poor overall survival in patients with cervical cancer. 10,11 However, the status of HPV DNA was only examined at a single time point after radiotherapy in those studies, and hence, the pattern of HPV clearance after radiotherapy and...