Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are surrogate markers of the systemic immune-inflammatory response proposed as perioperative prognostic biomarkers in epithelial ovarian cancer (EOC), yet their performance across subgroups remains unexamined. In 373 EOC patients undergoing primary cytoreductive surgery, postoperative day-1 changes (ΔSII, ΔNLR, ΔPLR) were compared for overall survival (OS) and progression-free survival (PFS) across 10 subgroups, and a Clinical-Inflammatory Risk Score (CIRS) combining inflammation with stage and residual disease was developed. Individual markers showed modest discrimination (area under the curve [AUC] 0.579–0.615); the marker with the highest AUC varied by context, with ΔPLR ranking first most often, notably in non-serous tumors, though none was statistically superior. Seeking a molecular counterpart, two public transcriptomic cohorts were re-analyzed: VWF was consistently higher in clear cell than serous carcinoma, whereas IL6–STAT3-related differences were cohort-dependent. The CIRS achieved AUCs of 0.752 (OS) and 0.764 (PFS), a six-fold mortality gradient (7.2% vs. 44.4%), and remained independently associated with OS and PFS (hazard ratio 2.55 and 2.24 per standard deviation), though discrimination was not significantly better than stage and residual disease alone. These biomarkers show subgroup-dependent prognostic value, and the CIRS provides an exploratory risk-stratification framework warranting prospective validation.

e17587 Background: Progression-free survival (PFS) is widely used as a surrogate endpoint for overall survival (OS) in ovarian cancer, but its validity varies across clinical contexts. To evaluate PFS–OS surrogacy using individual-level agreement in a large real-world cohort and trial-level correlation across randomized studies. Methods: An institutional cohort of 4,269 patients was analyzed to compare factor-specific hazard ratios (HRs) for PFS and OS and to quantify individual-level surrogacy using censored Kendall’s τ. Trial-level HRs were extracted from phase II/III ovarian cancer trials. Surrogacy was assessed using Spearman correlation, Bland–Altman agreement, and weighted meta-regression, with stratified analyses by disease setting, treatment modality, publication era, maintenance therapy, and HR_PFS thresholds. Results: In the institutional cohort, HR_PFS and HR_OS showed near-perfect concordance (R = 0.98) with minimal bias. Censored Kendall’s τ indicated strong individual-level correlation (τ = 0.78; p < 0.001), with 89% concordant event ordering. Across trials, PFS and OS demonstrated moderate correlation (ρ ≈ 0.62) with small mean bias but wide limits of agreement. Surrogacy was strongest in platinum-resistant disease and first-line cytotoxic chemotherapy, and weaker in platinum-sensitive and targeted therapy settings. Maintenance-therapy trials showed more stable agreement than non-maintenance trials. Temporal analyses revealed the most robust surrogacy in the 2010s, with attenuation in the 2020s as treatment heterogeneity increased. Conclusions: PFS is a practical but context-dependent surrogate for OS in ovarian cancer. Strong individual-level and HR-level concordance supports its use, although trial-level surrogacy varies by disease setting, treatment modality, and therapeutic era. Continued validation is essential as modern treatments reshape post-progression outcomes.

OBJECTIVE:The aim of this study was to validate a new Japanese risk grouping in the Korean population and to identify the group benefit from adjuvant treatment. METHODS:A total of 561 patients with stage IB cervical cancer who underwent radical hysterectomy with lymphadenectomy from 2000 to 2008 across 9 Korean Gynecologic Oncology Group-affiliated institutions were included in this study. Patients had at least one intermediate-risk factor: lymphovascular space invasion, outer one-third of the deep cervical stromal invasion, or a tumor 4 cm or larger. Disease-free survival (DFS) was analyzed based on adjuvant therapies: no treatment, radiation therapy, concurrent chemoradiation therapy or systemic chemotherapy. RESULTS:Patients were classified into 3 groups based on their histologically-incorporated intermediate risk factors. Group 1 included patients with limited risk factors (n=385, 68.6%), group 2 (n=106, 18.9%), and group 3 (n=70, 12.5%) had increasing risk. DFS differed across groups (group 1 vs. group 2, p=0.048; group 2 vs. group 3, p=0.030). Group 1 showed no DFS benefit from adjuvant treatment, while in groups 2 and 3, receiving radiation therapy improved DFS (group 2: adjusted hazard ratio [aHR]=0.09; 95% confidence interval [CI]=0.01-0.80; p=0.031 and group 3: aHR=0.21; 95% CI=0.04-1.08; p=0.047). In group 3, receiving concurrent chemotherapy treatment did not significantly affect DFS compared to radiation alone (aHR=0.84; 95% CI=0.11-6.30; p=0.861). CONCLUSION:This study revealed the prognostic value of histology-incorporated intermediate-risk stratification for early-stage cervical cancer in the Korean population. Unlike the results seen in Japanese populations, adjuvant treatment benefited higher-risk patients in terms of DFS.

OBJECTIVE:To introduce the temporary dual artery ligation (TDAL) technique and evaluate its. effectiveness in reducing intraoperative blood loss during laparoscopic myomectomy (LM). METHODS:We retrospectively reviewed 178 patients: 83 in the TDAL group and 95 in the Non-TDAL group. Leiomyoma burden indexes (dominant size, sum of diameters, total weight, and volume), surgical outcomes (operation time and hemoglobin [Hb] change), and perioperative complications were compared. Multivariate regression and receiver operating characteristic (ROC) curve analyses were performed to identify the optimal leiomyoma burden thresholds where TDAL was most effective. RESULTS:Total operative time was significantly longer in the TDAL group than in the Non-TDAL group (165.14 ± 53.08 vs. 144.21 ± 83.94 min, p = 0.036). However, the mean decrease in serum Hb level was significantly lower in the TDAL group (1.74 ± 0.92 vs. 2.08 ± 1.12 g/dL, p = 0.027). Multivariate analysis confirmed that TDAL was independently associated with a smaller perioperative Hb decline (β = -0.396, 95 % CI: -0.684 to -0.107, p = 0.007). Subgroup analyses using ROC-derived cut-off values revealed that TDAL significantly reduced blood loss in patients with a dominant leiomyoma ≥ 8 cm, a total sum of diameters ≥ 15 cm, or a resected weight ≥ 250 g. CONCLUSION:TDAL during LM effectively reduces intraoperative blood loss, particularly in patients with a high leiomyoma burden.

OBJECTIVE:To compare the oncologic outcomes of minimally invasive surgery (MIS) and abdominal hysterectomy in patients with low-risk, early-stage cervical cancer, based on the SHAPE trial eligibility criteria. METHODS:This retrospective study analyzed data from the Korean Gynecologic Oncology Group (KGOG) 1028 cohort, including patients with 2009 FIGO stage IB1 cervical cancer who met SHAPE trial criteria and underwent MIS or abdominal hysterectomy. Disease-free survival (DFS) was the primary outcome, whereas secondary outcomes included pelvic recurrence rates and prognostic factors influencing DFS. RESULTS:A total of 508 patients were included (82 in the MIS group and 426 in the abdominal hysterectomy group). The MIS group had significantly shorter DFS (median, 55.4 vs. 66.5 months, P = 0.024) and a higher pelvic recurrence rate (6.10 % vs. 1.88 %, P = 0.024). Multivariable Cox regression analysis identified MIS as an independent predictor of recurrence (HR, 3.26; 95 % CI, 1.054-10.061; P = 0.040), along with a larger tumor size (HR, 3.65 per 1 cm increase; 95 % CI, 1.300-9.854; P = 0.011) and older age (HR, 1.05 per year; 95 % CI, 1.002-1.096; P = 0.043). CONCLUSIONS:Even in low-risk, early-stage cervical cancer patients meeting SHAPE trial criteria, MIS was associated with shorter DFS and a higher pelvic recurrence risk than abdominal hysterectomy. These findings are consistent with concerns raised by the LACC trial, suggesting a potential oncologic disadvantage of MIS. Further prospective, randomized studies with standardized patient selection are needed to validate these results and guide decision-making.

BACKGROUND:Epithelial ovarian cancer is an aggressive malignancy with poor prognosis despite advances in multimodal treatment. The systemic immune-inflammation index (SII) has emerged as a prognostic biomarker in various cancers; however, the impact of surgery-induced inflammatory changes remains unclear. METHODS:This study evaluated the prognostic significance of postoperative changes in SII among patients with epithelial ovarian cancer undergoing primary surgery. Data from 374 patients treated at Samsung Medical Center and Kangbuk Samsung Hospital between 2016 and 2021 were retrospectively reviewed. SII was calculated from complete blood counts obtained within one month before surgery and on postoperative day 1. The percentage change in SII was analyzed, and the optimal cutoff was determined using receiver operating characteristic curve analysis. Survival outcomes were assessed using Kaplan-Meier and multivariable Cox regression models. RESULTS:Patients with a postoperative SII increase > 98.4% (Group 2) had significantly poorer overall (HR = 1.86, p = 0.009) and progression-free survival (HR = 1.30, p = 0.112) compared with those with smaller changes (Group 1). DISCUSSION:High-grade histology, serous subtype, and greater intraoperative blood loss were associated with higher postoperative SII. A marked postoperative increase in SII independently predicted poor survival, suggesting that dynamic inflammatory responses rather than static baseline levels provide additional prognostic information. CONCLUSIONS:Perioperative SII monitoring, easily obtainable from routine blood tests, may help identify high-risk patients who could benefit from intensified surveillance or adjuvant treatment. Prospective multicenter studies are warranted to validate these findings and explore whether perioperative modulation of systemic inflammation can improve outcomes.

Paclitaxel (PTX) is a widely used anticancer drug for ovarian cancer treatment, but its clinical application is limited by poor water solubility and dose-limiting toxicities. To overcome these challenges, we developed a thermoresponsive, multistep drug delivery system, pNIB/PTX, designed to improve PTX solubility and provide controlled drug release. The pNIB/PTX-3 complex exhibited an initial rapid drug release phase followed by sustained slow release, optimizing both short-term and long-term therapeutic efficacy. At physiological temperatures, the complex demonstrated a precisely controlled drug release mechanism driven by changes in the polymeric micelle structure. In vitro studies showed that pNIB/PTX-3 significantly enhanced therapeutic effects in human ovarian cancer cell lines HeyA8 and SKOV3ip1, compared to PTX alone. In orthotopic ovarian cancer mouse models, a single intraperitoneal injection of pNIB/PTX-3 led to a substantial reduction in tumor size and prolonged survival. This multistep, thermoresponsive delivery system shows strong potential as a promising therapeutic option for dose-dense ovarian cancer treatments, providing improved drug stability, controlled release, and minimized side effects.

Background: The aim of this study was to determine whether continuous wound infiltration (CWI) can replace intravenous patient-controlled analgesia (IV PCA) and to investigate effective pain control strategies after a single-port access (SPA) laparoscopy for adnexal disease. Methods: A total of 470 patients (the CWI group [n = 109], the IV PCA group [n = 198], and the combined group [n = 163]) who underwent an SPA adnexal laparoscopy and who received CWI or IV PCA for postoperative pain management were retrospectively reviewed. The numeric rating scale (NRS) pain score at 6, 12, 24, and 48 h (h) after surgery and the total amount of fentanyl administered via IV PCA were collected. The incidence of postoperative nausea and vomiting (PONV) and the total amount of rescue antiemetic drugs administered were also evaluated. Results: The mean NRS pain scores at 6 h (combined vs. PCA vs. CWI, 3.08 vs. 3.44 vs. 3.96, p < 0.001), 12 h (2.10 vs. 2.65 vs. 2.82, p < 0.001), and 24 h (1.71 vs. 2.01 vs. 2.12, p < 0.001) after surgery were significantly lower in the combined group. CWI showed a similar pain-reduction effect after surgery compared to IV PCA, except for the acute phase (within 6 h after surgery). The incidence of PONV during the entire hospitalization period was significantly lower in the CWI group compared to the groups using IV PCA (p < 0.05). The combined group had a significantly lower incidence of PONV and use of rescue antiemetics than the IV PCA group (p < 0.05). The combined group required significantly less total PCA fentanyl compared to the IV PCA group (combined vs. PCA, 622.1 μg vs. 703.1 μg, p < 0.001). Conclusions: CWI is an effective alternative to IV PCA and has fewer side effects. Combined use of CWI and IV PCA may be an ideal pain management strategy, offering a strong pain-reduction effect and only moderate side effects.

IntroductionSingle-port access (SPA) laparoscopy requires only one incision, unlike conventional laparoscopy. However, its umbilical incision is larger than that of conventional laparoscopy and can be vulnerable to postoperative pain. This study aimed to evaluate whether simultaneous use of a continuous wound infiltration (CWI) system and intravenous patient-controlled analgesia (IV PCA) effectively decreases surgical site pain in patients who underwent SPA laparoscopy due to gynecologic adnexal disease.MethodsA total of 371 patients who underwent SPA laparoscopy and who received IV PCA or CWI was retrospectively reviewed (combined group [CWI + IV PCA, n = 159] vs. PCA group [IV PCA only, n = 212]). To evaluate postoperative pain management, the numeric rating scale (NRS) pain score after surgery, total amount of fentanyl administered via IV PCA, and additional pain killer consumption were collected.ResultsThe NRS scores at 12 h (1.90 ± 1.11 vs. 2.70 ± 1.08, p < 0.001) and 24 h (1.82 ± 0.82 vs. 2.11 ± 1.44, p = 0.026) after surgery were significantly lower in the combined group than in the PCA group. The total amount of PCA fentanyl was significantly smaller in the combined group than in the PCA group (p < 0.001). The total quantity of rescue analgesics was smaller in the combined group than in the PCA group (p < 0.05).ConclusionCombined use of the CWI system and IV PCA is an effective postoperative pain management strategy in patient who underwent SPA laparoscopy for adnexal disease.

Among ovarian cancer patients with BRCA mutation or homologous recombination deficiency (HRD), the efficacy of Poly-ADP-ribose polymerase (PARP) inhibitors such as olaparib, niraparib, veliparib, and rucaparib has been proven in a number of clinical trials. BRCA mutation and HRD are currently indicated for PARP inhibitor maintenance treatment in ovarian cancer. HRD diagnostic tests examine various components, resulting in different HRD status definitions and, as a result, different treatment decisions. A number of HRD diagnostic tests exist, but test results provided by different companies may differ as they use different methods and different cutoffs. HRD prevalence difference was shown between PARP inhibitor maintenance trials. It is important to select an appropriate method that can present accurate HRD phenotypes to predict sensitivity to PARP inhibitors so that patients who are most likely to benefit from treatment are selected. Additionally, in the subset data of the PARP inhibitor maintenance trials, there was a difference in HRD prevalence by race as higher HRD prevalence in Japanese and Chinese ovarian cancer patients was shown. Further large-scale investigations on racial differences in HRD prevalence are needed and this may contribute to changes in determining the treatment plan and personalized treatment in ovarian cancer patients.

Background: Reduced-Port Robotic Surgery (RPRS) for myomectomy is feasible alternate method to overcome disadvantages of multiport and single-site platforms of robotic surgery with better cosmetic results. We demonstrated operative outcomes and long-term outcomes after RPRS. Methods: This is analysis of a prospective, non-randomized study of 115 patients who underwent RPRS from April 2016 through July 2021. Results: Overall 115 patients were included for analysis. Patients’ median age was 42 years (range, 28–52). The largest myoma was mostly located on the anterior uterine wall in 59 patients. The median myoma size and weight were 7.5 cm (range, 3–12) and 163 g (range, 42–753), respectively. The median myoma enucleation time and suture time were 10 minutes (range, 4–82) and 14 minutes (range, 5–63). Trend of shorter docking time and console time was shown with experience. The procedure was successfully performed via RPRS in 104 patients (91.5%); 10 patients required placement additional ports, conversion to open surgery was conducted in one case. There were 6 patients (5.2%) with postoperative complication with surgical wound infection (1.7%), bleeding (0.9%), peritonitis (1.7%), and pneumonia (0.9%). For long-term outcomes, 12 recurrences (10.4%) were observed in median follow-up of 25 months (range, 6–62 months). Total of 4 patients became pregnant after RPRS, and three patients had delivered with Caesarean section without complications. Conclusions: Our long-term results demonstrate the safety and feasibility of RPRS for uterine myomectomy as a valid treatment modality.

Abstract As an anti-cancer drug, paclitaxel (PTX) is known to be effective for treating patients with ovarian cancer. Not only do dose density and side effects of PTX represent a certain difficulty in chemotherapy, but also cause problems related to its poor water solubility during the administration. From the dose-density concept, we hypothesized that continuous release of PTX could increase the duration of exposure to tumor cells and may be an effective ovarian cancer treatment for patients. Herein, we developed highly water-soluble and multi-temperature-responsive PTX delivery systems to treat ovarian cancer. This was accomplished by entrapping the hydrophobic PTX in poly(NIPAAm-co-BVIm) micelles engineered to deliver drugs (pNIB/PTX). Specifically, the pNIB/PTX-3 complex containing 74 μg PTX loaded at 25 °C showed a rapid release of PTX initially (5.9 %/day) during the first five days at 37 °C. The release rates decreased (1.1 %/day) over the following month, indicating a multi-step release. In orthotopic ovarian cancer mouse models, the pNIB/PTX complex resulted in a six-fold greater therapeutic effect with a single intraperitoneal injection than weekly PTX treatment alone in vitro using two human ovarian cancer cell lines, HeyA8 and SKOV3ip. Moreover, the tumor weights in HeyA8 and SKOV3ip1 models were remarkably decreased with the pNIB/PTX complex compared to the controls. The good water solubility and temperature-dependent release of PTX carriers are highly effective for short-term and long-term delivery. This multi-step drug delivery may be used as a potential candidate for the treatment of patients with ovarian cancer.

BACKGROUND Although lysyl-tRNA synthetase (KARS1) is predominantly located in the cytosol, it is also present in the plasma membrane where it stabilizes the 67-kDa laminin receptor (67LR). This physical interaction is strongly increased under metastatic conditions. However, the dynamic interaction of these two proteins and the turnover of KARS1 in the plasma membrane has not previously been investigated. OBJECTIVE Our objective in this study was to identify the membranous location of KARS1 and 67LR and investigate if this changes with the developmental stage of epithelial ovarian cancer (EOC) and treatment with the inhibitor BC-K01. In addition, we evaluated the therapeutic efficacy of BC-K01 in combination with paclitaxel, as the latter is frequently used to treat patients with EOC. METHODS Overall survival and prognostic significance were determined in EOC patients according to KARS1 and 67LR expression levels as determined by immunohistochemistry. Changes in the location and expression of KARS1 and 67LR were investigated in vitro after BC-K01 treatment. The effects of this compound on tumor growth and apoptosis were evaluated both in vitro and in vivo. RESULTS EOC patients with high KARS1 and high 67LR expression had lower progression-free survival rates than those with low expression levels of these two markers. BC-K01 reduced cell viability and increased apoptosis in combination with paclitaxel in EOC cell xenograft mouse models. BC-K01 decreased membranous KARS1 expression, causing a reduction in 67LR membrane expression in EOC cell lines. BC-K01 significantly decreased in vivo tumor weight and number of nodules, especially when used in combination with paclitaxel. CONCLUSIONS Co-localization of KARS1 and 67LR in the plasma membrane contributes to EOC progression. Inhibition of the KARS1-67LR interaction by BC-K01 suppresses metastasis in EOC.

This study was performed to investigate the prevalence, clinical characteristics, and treatment response according to BRCA1 and BRCA2 (BRCA) mutations in Korean patients with epithelial ovarian cancer (EOC). Two-hundred and ninety-eight Korean women diagnosed with high-grade serous and/or endometrioid EOC from 2010 to 2015 were tested for germline and 86 specimens for somatic BRCA mutations, regardless of the family history. Clinical characteristics including survival outcomes were compared in patients with and without BRCA mutations (NCT02963688). A total of 43 different germline BRCA mutations were identified in 78 patients among 298 patients (26.2%). Somatic BRCA mutations were identified in 11 (12.8%) patients among patients without germline BRCA mutations. Haplotype analysis demonstrated no founder mutations in our Korean patient cohort. Insignificant differences in age at diagnosis, primary site, and residual disease after surgery were observed between patients with and without BRCA mutations. In multivariate analysis for overall survival (OS), the presence of BRCA mutation was significantly associated with OS (P = .049) in addition to platinum sensitivity (P < .001), indicating it is an independent prognostic factor for survival regardless of platinum sensitivity to first-line chemotherapy. In addition, a higher response rate to subsequent chemotherapy after recurrence was observed in EOC patients with BRCA mutations resulting in better OS. In the current study, the prevalence of BRCA mutations in Korean patients with EOC was higher than previously reported in other ethnic groups. We demonstrated characteristics and treatment response in Korean EOC patients with BRCA mutations. These findings may provide valuable information to be considered in future clinical trials including Asian patients.

Objective: Uterine artery ligation (UAL) at the time of myomectomy has shown to decrease blood loss during the operation. However, little is known about the efficacy and feasibility of UAL during single-port access (SPA) myomectomy. The present study was performed to investigate the clinical benefits of UAL in SPA myomectomy and to provide details of the surgical techniques. Materials and methods: A retrospective and comparative review on the surgical outcomes of the patients who underwent SPA myomectomy with UAL and those who underwent SPA myomectomy without UAL was conducted. UAL was performed at its origin from the internal iliac artery via a retroperitoneal approach. Results: A total of 56 women who received SPA myomectomy were reviewed (24 patients received SPA myomectomy with UAL while 32 patients received SPA myomectomy only). The median weight of total resected leiomyomas was heavier for the patients who received UAL than those who did not receive UAL [210.0 g (range: 171.5-335.0 g) vs. 119.0 g (62.5-265.0 g), p = 0.023]. However, no differences in total operative time, estimated blood loss, perioperative hemoglobin changes, use of postoperative analgesics and postoperative complications between the two groups were seen. Conclusion: Obtaining similar surgical outcomes between the patients who received UAL with larger leiomyomas and those who did not receive UAL with smaller leiomyomas suggests that UAL is a feasible surgical approach to reduce blood loss during SPA myomectomy. Detailed descriptions of the surgical techniques are provided in the present report. (C) 2021 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V.

ObjectiveBRCA1 expression can be lost by a variety of mechanisms including germline or somatic mutation and promotor hypermethylation. Given the potential importance of BRCA1 loss as a predictive and prognostic biomarker in several cancers, the objective of this study was to investigate BRCA1 expression using immunohistochemistry (IHC) in cervical cancer and its possible prognostic relevance.MethodsSeventy patients with cervical cancer were enrolled in this study. Samples from each tumor were stained for BRCA1 and reviewed independently by gynecologic pathologists blinded to the BRCA status. Kaplan–Meier methods were used to estimate overall survival according to BRCA1 expression. Differentially expressed genes (DEGs) by BRCA1 expression were selected using GSE44001 dataset, which included 300 samples treated with radical hysterectomy. In addition, cox regression analysis with backward elimination was performed to select independent prognostic markers. Gene set enrichment analysis (GSEA) was done using these DEGs.ResultsBRCA1 IHC was positive in 62.9% (44/70) of cases. Patients with BRCA1 expression showed better overall survival (100% vs. 76.2%, HR 0.20, 95% CI 0.04 – 0.99, p = 0.028) than those without BRCA1 expression. Analysis of gene expression profiles according to BRCA1 expression identified 321 differentially expressed mRNAs. Gene set enrichment analysis results showed two dysregulated pathways (VEGF_A_UP.V1_DN and E2F1_UP.V1_UP). Of these DEGs, alterations of 20 gene signatures were found to be independently associated with survival outcomes of patients.ConclusionsBRCA1 expression in cervical cancer tissue is associated with survival. In addition, the identification of specific gene alterations associated with BRCA1 expression could help to provide individualized prediction in these patients.

Overcoming drug-resistance is a big challenge to improve the survival of patients with epithelial ovarian cancer (EOC). In this study, we investigated the effect of chloroquine (CQ) and its combination with cisplatin (CDDP) in drug-resistant EOC cells. We used the three EOC cell lines CDDP-resistant A2780-CP20, RMG-1 cells, and CDDP-sensitive A2780 cells. The CQ-CDDP combination significantly decreased cell proliferation and increased apoptosis in all cell lines. The combination induced expression of γH2AX, a DNA damage marker protein, and induced G2/M cell cycle arrest. Although the CQ-CDDP combination decreased protein expression of ATM and ATR, phosphorylation of ATM was increased and expression of p21 WAF1/CIP1 was also increased in CQ-CDDP-treated cells. Knockdown of p21 WAF1/CIP1 by shRNA reduced the expression of γH2AX and phosphorylated ATM and inhibited caspase-3 activity but induced ATM protein expression. Knockdown of p21 WAF1/CIP1 partly inhibited CQ-CDDP-induced G2/M arrest, demonstrating that knockdown of p21 WAF1/CIP1 overcame the cytotoxic effect of the CQ-CDDP combination. Ectopic expression of p21 WAF1/CIP1 in CDDP-treated ATG5-shRNA/A2780-CP20 cells increased expression of γH2AX and caspase-3 activity, demonstrating increased DNA damage and cell death. The inhibition of autophagy by ATG5-shRNA demonstrated similar results upon CDDP treatment, except p21 WAF1/CIP1 expression. In an in vivo efficacy study, the CQ-CDDP combination significantly decreased tumor weight and increased expression of γH2AX and p21 WAF1/CIP1 in A2780-CP20 orthotopic xenografts and a drug-resistant patient-derived xenograft model of EOC compared with controls. These results demonstrated that CQ increases cytotoxicity in combination with CDDP by inducing lethal DNA damage by induction of p21 WAF1/CIP1 expression and autophagy inhibition in CDDP-resistant EOC.

Objective: To compare laparoscopic surgery to laparotomy for harvesting para-aortic lymph nodes in presumed stage I-II, high-risk endometrial cancer patients. Methods: Patients with histologically proven endometrial cancer, presumed stage I-II with high-risk tumor features who had undergone hysterectomy, bilateral salpingoophorectomy, or pelvic and para-aortic lymphadenectomy by either laparoscopy or laparotomy in Samsung Medical Center from 2005 to 2017 were retrospectively investigated. The primary outcome was para-aortic lymph node count. Secondary outcomes were pelvic lymph node count, perioperative events, and postoperative complications. Results: A total of 90 patients was included (35 for laparotomy, 55 for laparoscopy) for analysis. The mean (±SD) para-aortic lymph node count was 10.66 (±7.596) for laparotomy and 10.35 (±5.848) for laparoscopy (p = 0.827). Mean pelvic node count was 16.8 (±6.310) in the laparotomy group and 16.13 (±7.626) in the laparoscopy group (p = 0.664). Lower estimated blood loss was shown in the laparoscopy group. There was no difference in perioperative outcome between the groups. Additional multivariate analysis showed that survival outcome was not affected by surgical methods in presumed stage I-II, high-risk endometrial cancer patients. Conclusions: Study results demonstrate comparable para-aortic lymph node count with less blood loss in laparoscopy over laparotomy. In women with presumed stage I-II, high-risk endometrial cancer, laparoscopy is a valid treatment modality.