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Background To compare the diagnostic accuracy of aspiration biopsy and dilatation and curettage (D&C) in patients diagnosed with endometrial hyperplasia prior to hysterectomy. Methods We retrospectively reviewed medical records of 250 patients diagnosed with endometrial hyperplasia by endometrial sampling between July 2003 and March 2020. Endometrial sampling was performed by aspiration biopsy (n = 150) or D&C (n = 100), followed by hysterectomy within 6 months. Pathological findings of hysterectomy specimens of the two groups were compared to preoperative findings. Results The overall diagnostic concordance between endometrial sampling specimen including D&C and aspiration biopsy, and hysterectomy specimen was 51.0% (51/100) and 41.3% (62/150), respectively. Patients whose preoperative specimen was obtained by D&C were upgraded less significantly than those who underwent aspiration biopsy (21.0% vs 36.7%; P = 0.008). In particular, significantly fewer patients were upgraded after D&C than after aspiration biopsy in hyperplasia without atypia (12.5% vs 29.0%; P = 0.028). In addition, when the final pathological upgrade rate to endometrial carcinoma was evaluated between the two methods of endometrial sampling, significantly fewer cases were noted after D&C than after aspiration biopsy (15.0% vs 27.3%; P = 0.022). Conclusions In our study, D&C more accurately reflected the final diagnosis in patients with endometrial hyperplasia than aspiration biopsy based on the histological examination of hysterectomy specimens. When considering the management strategy for women with an endometrial hyperplasia diagnosis obtained by aspiration biopsy, physicians should consider the significant rate of upgraded diseases with this method of endometrial sampling.

Background To determine if extended chemotherapy improves survival outcomes in patients with platinum-sensitive relapsed epithelial ovarian cancer (EOC) who have residual disease after six cycles of second-line chemotherapy. Methods In this study, 135 EOC patients who experienced platinum-sensitive recurrence after primary treatment between 2008 and 2018, and had a residual tumor ≥0.5 cm (detected on CT scans) after completing six cycles of second-line, platinum-based chemotherapy, were retrospectively reviewed. Based on the number of main therapy cycles (second-line chemotherapy), we divided patients into an extended group (>6 cycles, n = 52) or a standard group (6 cycles, n = 83) and compared patient characteristics and survival outcomes between these groups. Results The extended group had a shorter platinum-free interval after primary treatment than the standard group (median, 11.0 vs. 13.1 months; P = 0.018). Secondary debulking surgery was less frequently performed in the standard group (1.9% vs. 19.3%; P = 0.003). After six chemotherapy cycles, the extended and standard groups showed similar serum CA-125 levels (P = 0.122) and residual tumor sizes (P = 0.232). There was no difference in overall survival (OS) between the groups (P = 0.382), although the extended group had significantly worse progression-free survival (PFS) than the standard group (median, 13.9 vs. 15.1 months; P = 0.012). Multivariate analyses revealed that platinum-free interval was an independent prognostic factor for PFS and OS, but extended chemotherapy was not (PFS: HR, 1.25; 95% CI, 0.84–1.85; P = 0.279; and OS: HR, 1.36; 95% CI, 0.72–2.56; P = 0.342). We observed consistent results in the subset of patients who did not undergo secondary debulking surgery. Conclusions More than six cycles of platinum-based chemotherapy might not improve survival outcomes in patients with platinum-sensitive recurrent EOC who had a residual tumor ≥0.5 cm after six cycles of second-line chemotherapy.

Aim The aim of the study was to estimate the prevalence of pelvic insufficiency fractures (PIFs) after radiation therapy (RT) in patients with cervical cancer. Patients and methods A total of 3,633 patients from 15 cohort studies were included. Proportion meta-analysis was performed to estimate prevalence and subgroup analysis was performed according to imaging modalities for diagnosis of PIF. For continuous variables (age and length of follow-up), meta-regression analysis was performed. Results Pooled prevalence estimate of PIF was 14% (95% CI=10-19). Incidence of PIF was higher in studies that used MRI as a diagnostic tool (17%, 95% CI=12-22) than non-MRI (8%, 95% CI=2-14). In meta-regression, we found a significant association of prevalence of PIF with age (p=0.021) but not with length of follow-up (p=0.118). Conclusion PIF after RT in patients with cervical cancer is not rare. Physicians need to pay attention to PIFs, especially in patients with high-risk factors for osteoporotic fracture.

Background Human epididymis protein 4 (HE4) is a tumor marker that has been well-investigated in ovarian and endometrial cancers. The aim of this study was to evaluate the prognostic value of serum HE4 as a tumor marker in patients with cervical cancer. Methods Serum HE4 levels from 67 cervical cancer patients were measured by immunoassay before starting primary treatment between September 2014 and May 2018. A mean serum HE4 level of 72.6 pmol/L was used to divide the patients into low and high HE4 groups. The patient characteristics, clinicopathological variables, and survival outcomes were compared between the 2 groups. Results There were 55 (82.1%) patients in the HE4 72.6 pmol/L group at the date of diagnosis. Higher HE4 levels were significantly associated with older age at diagnosis (age

This study investigated the antitumor activity and safety of pembrolizumab in patients with recurrent cervical cancer in real-world practice. We conducted a multi-center retrospective study of patients with recurrent or persistent cervical cancer treated with pembrolizumab at sixteen institutions in Korea between January 2016 and March 2020. The primary endpoints were the objective response rate (ORR) and safety. Data were available for 117 patients. The median age was 53 years (range, 28&ndash, 79). Sixty-four (54.7%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of &ge, 2. Forty-nine (41.9%) patients were stage &ge, III at diagnosis. Eighty-eight (75.2%) patients had squamous cell carcinoma. The median number of prior chemotherapy lines was two (range, 1&ndash, 6). During the median follow-up of 4.9 months (range, 0.2&ndash, 35.3), the ORR was 9.4%, with three complete responses and eight partial responses. The median time to response was 2.8 months (range 1.3&ndash, 13.1), and the median duration of response (DOR) was not reached. In the population of patients with favorable performance status (ECOG &le, 1) (n = 53), the ORR was 18.9%, and the median DOR was 8.9 months (range, 7.3&ndash, 10.4). Adverse events occurred in 55 (47.0%) patients, including eight (6.8%) patients who experienced grade &ge, 3 events, and two of them were suspicious treatment-related deaths. Pembrolizumab had modest antitumor activity in patients with recurrent cervical cancer comparable to that found in previously reported clinical trials. However, in patients with favorable performance status, pembrolizumab showed effective antitumor activity. Some safety profiles should be carefully monitored during treatment.

The aim of the present study was to investigate the prognostic role of the pre-treatment complete blood count (CBC) profile as a predictive marker of survival, recurrence, and death in early stage squamous cell carcinoma and adenocarcinoma of the cervix. The pre-treatment CBC profiles of the patients from nine tertiary medical centers in South Korea who were treated surgically for early stage cervical cancer were reviewed. Statistical models by the Akaike&rsquo, s information criterion (AIC) were developed using CBC profiles to calculate individuals&rsquo, risk scores for clinical outcomes. A total of 1443 patients were included in the study and the median follow-up was 63.7 months with a range of 3&ndash, 183 months. Univariate analyses identified the components of CBC that were significantly related to clinical outcomes including white blood cell (WBC), hemoglobin, neutrophil, and platelet levels. The models developed using CBC profiles and the conventional clinical predictive factors provided individuals&rsquo, risk scores that were significantly better in predicting clinical outcomes than the models using the conventional clinical predictive factors alone. Pre-treatment CBC profiles including WBC, hemoglobin, neutrophil, lymphocyte, and platelet levels were found to be a potential biomarker for survival prognosis in early cervical cancer.

Autophagy is a catabolic process and has an important homeostatic role, mediating the removal of dysfunctional or superfluous proteins and organelles. Dysfunction of autophagy is involved in various physiologic and pathologic conditions, such as developmental cell death, clearance of pathogens, aging process, neurodegenerative diseases, and cancers. Cancer cells which are inherently vulnerable to metabolic stress and also defective in apoptosis are more dependent on autophagy for cell survival than normal cells. Autophagy might have a dual but conflicting role in carcinogenesis, tumor-suppressing and tumor-promoting role. The roles of autophagy in specific type cancers in vivo, however, have not been determined clearly. In this review, we discussed the role of autophagy especially in ovarian cancer cells in relation to cancer cell metabolism and its modulation by natural compounds.

IntroductionThe anterior vaginal wall is the segment most commonly affected by prolapse. Traditionally, anterior vaginal wall prolapse is repaired via anterior colporrhaphy, which is known to have a high recurrence rate. Several factors might affect the outcome of anterior colporrhaphy, and the use of absorbable sutures might also be associated with the high recurrence rate because the sutures might not be able to retain adequate strength until the plicated pubocervical fascia remodels and regains maximum tensile strength. Nonetheless, no comparative data exist about the relative efficacy and safety of anterior colporrhaphy using non-absorbable versus absorbable sutures. The objective of this study is to compare the surgical outcomes of anterior colporrhaphy using non-absorbable sutures with those of anterior colporrhaphy using absorbable sutures.Methods and analysisThis is a randomised, multicentre, superiority trial. Anterior colporrhaphy will be performed in a traditional manner with midline plication of the fibromuscular layer using either non-absorbable or absorbable sutures. The primary outcome is composite surgical success 1 year after surgery defined as the absence of all of the following: (1) anterior vaginal descent beyond the hymen, (2) the presence of vaginal bulge symptoms and (3) retreatment for recurrent anterior vaginal wall prolapse with either surgery or pessary. The secondary outcomes include the individual components of the composite primary end point, anatomical outcomes, condition-specific quality of life and adverse events related to anterior colporrhaphy. The planned number of participants is 192.Ethics and disseminationThis study was approved by the Institutional Review Board of Seoul National University Hospital (H-1810-037-977). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings.Trial registration numberNCT03736811

In 2019, 12 topics were selected as the major research advances in gynecologic oncology. Herein, we first opted to introduce the significant clinical activity of pembrolizumab in women with advanced cervical cancer based on the results of the phase 2 KEYNOTE-158 trial. Thereafter, we reviewed 5 topics, including systemic lymphadenectomy in the advanced stage with no gross residual tumor, secondary cytoreductive surgery in recurrent ovarian cancer according to the results of Gynecologic Oncology Group-213 trial, dose-dense weekly paclitaxel scheduling as first-line chemotherapy, the utility of intraperitoneal therapy in the advanced stage, and an update on poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Additionally, we conducted a thorough review of emerging data from several clinical trials on PARP inhibitors according to drug, target population, and combined usage. For uterine corpus cancer, we reviewed adjuvant therapy for high-risk disease and chemotherapy in advanced/recurrent disease. For the field of radiation oncology, we discussed the utility of neoadjuvant chemotherapy added to chemoradiotherapy and the treatment of radiation-induced cystitis using hyperbaric oxygen. Finally, we discussed the use of individualized therapy with humanized monoclonal antibodies (trastuzumab emtansine and sacituzumab govitecan-hziy) and combination therapy (fulvestrant plus alpesilib, fulvestrant plus anastrozole, and ribociclib plus endocrine therapy) for women with advanced breast cancer.

This corrects the article on p. e65 in vol. 31, PMID: 32342678.

IntroductionTransvaginal reconstructive surgery is the mainstay of treatment for symptomatic pelvic organ prolapse. Although adequate support for the vaginal apex is considered essential for durable surgical repair, the optimal management of anterior and posterior vaginal wall prolapse in women undergoing transvaginal apical suspension remains unclear. The objective of this trial is to compare surgical outcomes of pelvic organ prolapse quantification (POPQ)-based surgery with outcomes of simulated apical support-based surgery for anterior or posterior vaginal wall prolapse at the time of transvaginal apical suspension.Methods and analysisThis is a randomised, multicentre, non-inferiority trial. While women who are assigned to the POPQ-based surgery group will undergo anterior or posterior colporrhaphy for all stage 2 or greater anterior or posterior vaginal prolapse, those assigned to simulated apical support-based surgery will receive anterior or posterior colporrhaphy only for the prolapse unresolved under simulated apical support. The primary outcome measure is the composite surgical success, defined as the absence of anatomical (anterior or posterior vaginal descent beyond the hymen or descent of the vaginal apex beyond the half-way point of vagina) or symptomatic (the presence of vaginal bulge symptoms) recurrence or retreatment for prolapse by either surgery or pessary, at 2 years after surgery. Secondary outcomes include the rates of anterior or posterior colporrhaphy, the changes in anatomical outcomes, condition-specific quality of life and sexual function, perioperative outcomes and adverse events.Ethics and disseminationThis study was approved by the institutional review board of each participating centre (Seoul National University College of Medicine/Seoul National University Hospital, Chonnam National University Hospital, Seoul St. Mary’s Hospital, International St. Mary’s Hospital). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings.Trial registration numberNCT03187054

Objective: To investigate pathologic discrepancies between colposcopy-directed biopsy (CDB) of the cervix and loop electrosurgical excision procedure (LEEP) in women with cytologic high-grade squamous intraepithelial lesions (HSILs). Methods: We retrospectively identified 297 patients who underwent both CDB and LEEP for HSILs in cervical cytology between 2015 and 2018, and compared their pathologic results. Considering the LEEP to be the gold standard, we evaluated the diagnostic performance of CDB for identifying cervical intraepithelial neoplasia (CIN) grades 2 and 3, adenocarcinoma in situ, and cancer (HSIL+). We also performed age subgroup analyses. Results: Among the study population, 90.9% (270/297) had pathologic HSIL+ using the LEEP. The diagnostic performance of CDB for identifying HSIL+ was as follows: sensitivity, 87.8%; specificity, 59.3%; balanced accuracy, 73.6%; positive predictive value, 95.6%; and negative predictive value, 32.7%. Thirty-three false negative cases of CDB included CIN2,3 (n=29) and cervical cancer (n=4). The pathologic HSIL+ rate in patients with HSIL- by CDB was 67.3% (33/49). CDB exhibited a significant difference in the diagnosis of HSIL+ compared to LEEP in all patients (p

Aim To evaluate the effectiveness of adjuvant treatment for morcellated, uterus-confined leiomyosarcoma in a multicenter setting. Methods We identified patients with International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma primarily treated with surgery between 2003 and 2016. Among them, patients who underwent one of the following morcellation methods were included: (i) power morcellation; (ii) intracorporeal morcellation using scalpels or electrocautery; and (iii) vaginal morcellation. Patients' survival outcomes were compared according to the implementation of adjuvant treatment. Results From 13 institutions, 55 patients were included; 31 for adjuvant treatment group and 24 for surgery only group. The clinicopathological characteristics including the mass size, morcellation methods, extent of surgery, and mitotic count were similar between the groups. In the adjuvant treatment group, 67.7%, 19.4% and 12.9% of patients received chemotherapy, chemoradiation and radiation, respectively. After a median follow-up of 50.5 months, the adjuvant treatment and surgery only groups showed similar overall survival (5-year rate, 92.0% vs 90.4%; P = 0.959). No significant difference in progression-free survival was observed between the two groups (3-year rate, 46.1% vs 78.2%; P = 0.069). On multivariate analyses, adjuvant treatment did not affect progression-free survival (adjusted HR, 2.138; 95% CI, 0.550-8.305; P = 0.273). The adjuvant treatment group showed a trend towards more common distant metastasis, compared to the surgery only group (25.8% vs 4.2%; P = 0.062). The incidences of pelvic, retroperitoneal, and abdominal recurrences were not different between the groups. Conclusion Despite its frequent use in clinical practice, adjuvant treatment did not improve the survival outcomes of patients with morcellated, International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma.

The valorization of waste is of prime importance for sustainable chemistry and replacement of fossil fuel-derived counterparts. However, existing synthetic methods are critically hampered by complicated and uncontrollable chemistry arising from heterogeneous sources. Herein, we demonstrate a separation-free, straightforward, and controllable chemical approach for the valorization of lignocellulosic biomass by conversion to heteroatom-doped and undoped carbon dots (CDs) and nanoporous carbons (CNs) via a novel mechanism. The incorporation of heteroatoms such as phosphorus (P), sulfur (S), and nitrogen (N) into the CDs and steam-activated CNs (aCNs) leads to changes in the electronic and surface properties, and affords morphological control based on the doping agents, for application to CO2 capture and supercapacitors. Controlling the chemical composition and structure of the CDs results in shifts and variations in the splittings of the PL peaks and fluorescence wavelength owing to the distinct optoelectronic features. The P, N, and S-doped aCNs (P-aCN, S-aCN, and N-aCN) have robust honeycomb, entirely exfoliated reed-like, and hollow isolated reed-like structures, respectively, with unique hierarchical porosity. N-aCN exhibits the highest CO2 capacity and regeneration capability owing to the existence of basic N-containing groups and the associated structural integrity. In terms of the supercapacitive performance, P-aCN achieves the highest capacitance owing to the pseudocapacitance of the P˭O bonds, whereas S-aCN leads to the best rate and cyclic capabilities owing to the unique porous structure and S-containing group. These distinctive energy and chemical storage behaviors of the CNs highlight the importance of controlling hierarchical structure and heteroatoms for improved ultracapacitive performance.

Despite the significant impact of sodium (Na) storage systems in terms of natural abundance and environmental friendliness, high-performance pseudocapacitive mterials in organic electrolytes remain challenging. Here, we demonstrate the pseudocapacitive Na-ion storage of hierarchically structured, phosphorus-incorporating steam-activated nanoporous carbons (P-aCNs) with improved rate and cyclic capabilities in organic electrolytes. The P-aCNs with a hierarchical honeycomb structure are derived from lignocellulosic biomass via a proposed synthetic process. The prominent pseudocapacitive behaviors of the P-containing groups in organic Na-ion electrolytes are confirmed by the surface area-independent and surface-confined capacitances, distinctive redox waves, and strong binding with Na-ions. In particular, the P-aCN demonstrates the cyclic stability of 96.0% over 100 000 cycles in the full cell, achieving a high capacitance of 265.43 F g–1 and rate capability of 75%. These Na-ion pseudocapacitive features of ...

Objectives In sacrococcygeal teratoma, the presence of high-output cardiac failure resulting from arteriovenous shunting through the large tumor has been associated with an adverse outcome. The objective of this study was to determine whether the tumor size and cardiac biomarkers in cord blood can predict neonatal survival in sacrococcygeal teratoma. Methods The study population consisted of 25 neonates with sacrococcygeal teratoma. Tumor size was calculated by the ellipsoid formula using dimensions measured by antenatal ultrasound ([length × width × depth in cm] × 0.52= volume in cm3 ). To adjust the gestational age, the tumor volume index (tumor volume/biparietal diameter) was adopted in the analysis. Cardiac biomarkers for heart failure (N-terminal pro-B-type natriuretic peptide [NT-pro-BNP] and cardiac troponin T [cTnT]) were measured in cord blood taken at the time of delivery. Results The rate of neonatal death was 24% (6 of 25). The cases that resulted in neonatal death had a higher tumor volume index and higher concentrations of NT-pro-BNP and cTnT than those with survival. A tumor volume index of greater than 60 cm3 /cm, elevated NT-pro-BNP (>2000 pg/mL), and elevated cTnT (>0.08 ng/mL) had sensitivity of 100% for prediction of neonatal death. Conclusions The tumor volume index and cord blood biomarkers for heart failure can be promising prognostic markers for neonatal survival in sacrococcygeal teratoma.

Aim To investigate whether a concern for future pregnancy is reflected in the extent of large loop excision of the transformation zone (LLETZ) and to assess the clinical outcome. Methods We reviewed the medical records of 275 women who underwent LLETZ for precancerous lesions in cervix. We divided them into two groups according to pregnancy possibility in the future: nonpotential versus potential group. The potential group was arbitrarily defined as women who met one of the following: (i) regardless of marital status, younger than 41 years with less than two parities and (ii) regardless of parity, younger than 46 years and unmarried. After propensity score matching (1:1, 44 women in each group), we compared the extent of LLETZ with respect to short-term recurrence. Results After LLETZ, similar percentages of patients were finally diagnosed with ≥CIN3 (cervical intraepithelial neoplasia 3) in the two groups (27 [61.4%] vs 32 [72.7%], P = 0.257). Notably, the largest transverse diameter of LLETZ specimen was significantly larger in the nonpotential group (2.74 ± 1.06 vs 2.37 ± 0.62 cm, P = 0.047). There were more women with exocervical resection margin involvement in the potential group than in the nonpotential group (14 [31.8%] vs 6 [13.6%], P = 0.042). However, there was no significant difference in the incidence of short-term recurrence ≥HSIL (high-grade squamous intraepithelial lesion) within 24 months after LLETZ between the two groups (1 [2.3%] vs 1 [2.3%], P > 0.999). Conclusion Pregnancy possibility in the future may affect the extent of LLETZ, as assessed by the largest transverse diameter obtained. This finding may be associated with increased resection margin involvement in women with future pregnancy possibility.

The design of cost-effective and highly active catalysts is a critical challenge. Inspired by the strong points of stability and conductivity of carbon nanotubes (CNTs), high catalytic activity of Co nanoparticles, and rapid ion diffusion and large accessible area of three-dimensional (3D) graphene, we demonstrate a novel strategy to construct a hierarchical hybrid structure consisting of Co/CoOx nanoparticles-incorporated CNT branches onto the 3D reduced graphene oxide (rGO) architecture. The surface-modified 3D rGO by steam activation process has a large surface area and abundant defect sites, which serve as active sites to uniformly grow Co/CoOx nanoparticles. Furthermore, the CNTs preserve their performance stably by encapsulating Co nanoparticles, while the uniformly decorated Co/CoOx nanoparticles exhibit superior electrocatalytic activity toward oxygen evolution/reduction reaction due to highly exposed active sites. Employing the hybrid particle electrocatalyst, the seawater battery operates stably at 0.01 mA cm−2 during 50 cycles, owing to the good electrocatalytic ability.

Introduction: Based on molecular classification of endometrial cancer (EC) of The Cancer Genome Atlas (TCGA) and Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), EC has been classified into four novel prognostic groups: POLE-mutated (POLE-mt), mismatch repair-deficient (dMMR), copy number-high (p53abn), and copy number-low (no specific molecular profile, NSMP). We hypothesized that spatial distribution of tumor-infiltrating lymphocyte (TIL) using an artificial-intelligence (AI)-powered tissue analyzer, Lunit SCOPE, would be distinct according to the molecular classification. Methods: We analyzed EC of TCGA database (N=224) and EC tissues retrospectively collected from Seoul National University Bundang Hospital (SNUBH, N=236). EC from SHUBH were molecularly classified in which MMR and p53 status were determined by immunohistochemistry (IHC) and POLE mutation by digital droplet polymerase chain reaction of six hotspot mutations in exon 9, 13 and 14 (P286R, S297F, V411L, V424I, L424V, and A456P). Lunit SCOPE analysis to detect lymphocyte, cancer epithelium (CE), and cancer-associated stroma (CS) was performed using x40 scanned images of TCGA and SNUBH. Cox proportional hazard model were used for survival analysis. Results: Composition of molecular classification were comparable in both cohorts: 7.6%, 28.6%, 24.6%, and 39.3% for POLE-mt, dMMR, CN-high, and CN-low in TCGA cohort, and 8.9%, 19.5%, 17.4%, and 54.2% for POLE-mt, dMMR, p53abn, and NSMP in SNUBH cohort, respectively. CN-high subtype in TCGA and p53abn in SNUBH cohort significantly correlated with poor prognosis (TCGA: adjusted hazard ratio 2.54, p value 0.0383; SNUBH: adjusted hazard ratio 7.47, p value 2.38 x 10-4). TIL density calculated by total number of lymphocytes in CE and CS area was significantly increased in POLE and MSI groups of TCGA-cohort (p value = 2.24 x 10-4) and SNUBH-cohort (p value = 1.74 x 10-6). Moreover, uneven TIL enrichment in CS was observed in CN-high or TP53-expressor compared to CN-low or TP53-wildtype (ratio of TIL in CS/TIL in CE, TCGA: 6.96 versus 5.33; SNUBH: 11.4 versus 8.83). These findings suggested that the CN-high/p53abn and POLE/dMMR subtypes might be associated with immune-excluded and immune-inflamed tumor microenvironment (TME) phenotype, respectively. Conclusion:The distribution of TIL in EC differs according to the molecular subtypes. Our data suggest the possibility of predicting subtypes through TIL analysis, and provide insight into treatment through TME modulation. Citation Format: Hyojin Kim, Eun Sun Kim, Song Kook Lee, Jeong Hoon Lee, Kyunghyun Paeng, Chan-Young Ock, Dong Hoon Suh, Kidong Kim, Jae Hong No, Yong-Beom Kim. Artificial intelligence-powered tissue analysis reveals distinct tumor-infiltrating lymphocyte profile as a potential biomarker of molecular subtypes in endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 617.

Objective The purpose of this study is to estimate the risk of postoperative lymphocele development after lymphadenectomy in gynecologic cancer patients through establishing a nomogram. Methods We retrospectively reviewed 371 consecutive gynecologic cancer patients undergoing lymphadenectomy between 2009 and 2014. Association of the development of postoperative lymphocele with clinical characteristics was evaluated in univariate and multivariate regression analyses. Nomograms were built based on the data of multivariate analysis using R-software. Results Mean age at the operation was 50.8±11.1 years. Postoperative lymphocele was found in 70 (18.9%) patients. Of them, 22 (31.4%) had complicated one. Multivariate analysis revealed that hypertension (hazard ratio [HR], 3.0; 95% confidence interval [CI], 1.5 to 6.0; P=0.003), open surgery (HR, 3.2; 95% CI, 1.4 to 7.1; P=0.004), retrieved lymph nodes (LNs) >21 (HR, 1.8; 95% CI, 1.0 to 3.3; P=0.042), and no use of intermittent pneumatic compression (HR, 2.7; 95% CI, 1.0 to 7.2; P=0.047) were independent risk factors for the development of postoperative lymphocele. The nomogram appeared to be accurate and predicted the lymphocele development better than chance (concordance index, 0.754). For complicated lymphoceles, most variables which have shown significant association with general lymphocele lost the statistical significance, except hypertension (P=0.011) and mean number of retrieved LNs (29.5 vs. 21.1; P=0.001). A nomogram for complicated lymphocele showed similar predictive accuracy (concordance index, 0.727). Conclusion We developed a nomogram to predict the risk of lymphocele in gynecologic cancer patients on the basis of readily obtained clinical variables. External validation of this nomogram in different group of patients is needed.

// Dong Hoon Suh 1 , Miseon Kim 1 , Jin Young Choi 1 , Jiyoon Bu 2 , Yoon-Tae Kang 2 , Byung Su Kwon 3 , Banghyun Lee 4 , Kidong Kim 1 , Jae Hong No 1 , Yong-Beom Kim 1 and Young-Ho Cho 2 1 Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea 2 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea 3 Department of Obstetrics and Gynecology, Pusan National University Hospital, Busan, Korea 4 Department of Obstetrics and Gynecology, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea Correspondence to: Yong-Beom Kim, email: ybkimlh@snubh.org Keywords: ovarian neoplasm, circulating tumor cell, preoperative period, differential diagnosis, early stage cancer Received: January 02, 2017 Accepted: June 27, 2017 Published: August 24, 2017 ABSTRACT The aim of this study was to evaluate circulating tumor cell (CTC) detection in the differential diagnosis of adnexal masses. A total of 87 preoperative women with an indeterminate adnexal mass were prospectively enrolled. Preoperative diagnostic modalities including CTC detection, risk of ovarian malignancy algorithm, risk of malignancy index, and computed tomography or magnetic resonance imaging were compared. Forty-three (49.4%) benign tumors, 13 (14.9%) borderline malignant masses, and 31 (35.7%) cancers were pathologically confirmed. Forty-nine (56.3%) cases were positive for CTCs: 19/43 (44.2%) benign, 10/10 (100%) early-stage, and 14/21 (66.7%) advanced-stage cancer. CTC detection had sensitivities of 77.4%, 100%, and 100% for benign vs. all stage cancer (n = 74), benign vs. stage I–II cancer (n = 53), and benign vs. stage I cancer (n = 49), respectively. CTC detection had a specificity of 55.8% across all comparisons. The sensitivities of the other modalities assayed were decreased in stage I–II cancer and stage I cancer vs. benign masses. Receiver operating characteristic curves showed that CTCs, of which the area under the curve was modest in all stage cancer (0.655), had the widest area under the curve among the evaluated modalities in stage I–II cancer and stage I cancer (0.768 for both). In conclusion, our study findings suggest that preoperative CTCs could have a substantial role in differentiating early stage cancer from benign tumors for adnexal masses.

// Boyun Kim 1, 2 , Je Won Jung 3 , Jaeyoung Jung 1, 4 , Youngjin Han 1, 4 , Dong Hoon Suh 5 , Hee Seung Kim 7 , Danny N. Dhanasekaran 6 and Yong Sang Song 1, 4, 7 1 Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Korea 2 Nano System Institute, Seoul National University, Seoul 08826, Korea 3 Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea 4 WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea 5 Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam 13620, Korea 6 Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73012, United States of America 7 Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul 03080, Korea Correspondence to: Yong Sang Song, email: yssong@snu.ac.kr Keywords: ovarian cancer, ROS, PGC1α, chemoresistance, mitochondria Received: November 16, 2016 Accepted: June 10, 2017 Published: July 10, 2017 ABSTRACT Malignant cells are subjected to high levels of oxidative stress that arise from the increased production of reactive oxygen species (ROS) due to their altered metabolism. They activate antioxidant mechanisms to relieve the oxidative stress, and thereby acquire resistance to chemotherapeutic agents. In the present study, we found that PGC1α, a key molecule that both increases mitochondrial biogenesis and activates antioxidant enzymes, enhances chemoresistance in response to ROS generated by exposure of cells to ovarian sphere-forming culture conditions. Cells in the cultured spheres exhibited stem cell-like characteristics, and maintained higher ROS levels than their parent cells. Intriguingly, scavenging ROS diminished the aldehyde dehydrogenase (ALDH)-positive cell population, and inhibited proliferation of the spheres. ROS production triggered PGC1α expression, which in turn caused changes to mitochondrial biogenesis and activity within the spheres. The drug-resistant phenotype was observed in both spheres and PGC1α-overexpressing parent cells, and conversely, PGC1α knockdown sensitized the spheres to cisplatin treatment. Similarly, floating malignant cells derived from patient ascitic fluid included an ALDH-positive population and exhibited the tendency of a positive correlation between expressions of multidrug resistance protein 1 (MDR1) and PGC1α. The present study suggests that ROS-induced PGC1α mediates chemoresistance, and represents a novel therapeutic target to overcome chemoresistance in ovarian cancer.

This randomized trial investigated whether a 2-dose administration of intravenous ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective than a single-dose administration in preventing postoperative nausea and vomiting (PONV) in 89 patients who were scheduled to undergo laparoscopic operation for benign gynecologic diseases and to receive intravenous patient-controlled analgesia for relief of postoperative pain. After assignment at a ratio of 1:1, intravenous ramosetron (0.3 mg) was initially administered at the end of skin closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were administered to the study and control groups, respectively, at 4 hours after the operation. The baseline and operative characteristics were similar between the groups. The incidence of PONV during the 24-hour period after operation which was assessed as the primary endpoint did not differ between the groups. No serious adverse events occurred in either group. A 2-dose administration of intravenous ramosetron may not be superior to a single-dose administration in preventing PONV in patients undergoing laparoscopic operation for benign gynecologic diseases.

We demonstrate the microwave synthesis of tin oxide (SnO 2 ) nanoparticles and direct deposition on the surface of restacking inhibited reduced graphene oxide (rGO) nanosheets for an application into lithium ion battery anodes. The mesoporous rGO-SnO 2 nano-composite (G-SnO 2 ), where the SnO 2 nanoparticles are intercalated in the layer-by-layer structure of the restacking rGO nanosheets, can be synthesized within 10 min by microwave irradiation, simultaneously promoting the reduction of graphene oxides (GO). The size of SnO 2 nanoparticles ranges from 5 to 10 nm and they are highly crystalline structure along with the change in the oxidation states from Sn 2+ to Sn 4+ in the process of the microwave synthesis. The G-SnO 2 anodes show 1200 mAh g −1 at 50 mA g −1 and their specific capacity is preserved up to 1000 mAh g −1 during the 100 cycles. The coulombic efficiency keeps 97% after the 1st cycle and the high specific capacity of 747 mAh g −1 is maintained with 66.3% of capacity retention even when the current density increases from 50 mA g −1 to 300 mA g −1 . These results indicate that the improvement of specific capacity, rate capability and cycle stability is attributed to the mesoporous layer-by-layer structure of G-SnO 2 , where the well-defined SnO 2 nanoparticles are deposited on the restacking inhibited rGO nanosheets.

Background Management of atypical femoral fracture on bisphosphonate therapy still remains controversy and is reported high rate of complications. The aim of this study was to evaluate the outcome of intramedullary nailing in patients with atypical femoral fracture who took bisphosphonate more than one year through the multicenter retrospective study. Methods We gathered 75 atypical femoral fractures from seven institutions between 2009 and 2014. Among them 46 atypical femoral fractures which met the inclusion criteria was evaluated in this study. The average age was 70.1 years (53–80) and the average duration of bisphosphonate use was 5.1 years (1–15 years). Medical records and radiographs were reviewed to determine time to union, union rate, need for revision surgery, restoration of ambulatory function, and complications. Results Twenty-nine (63%) fractures healed within 6 months without complications. The average time to union except two non-union was 24.9 weeks (11–48 weeks). Two patients (4.3%) underwent revision surgery for non-union and there was no implant failure. Thirty-seven (80.4%) patients achieved their pre-fracture ambulatory function at the final follow up. Conclusions Although the incidence of delayed bone healing is high in atypical femoral fracture on bisphosphonate therapy even treated with intramedullary nailing, the incidence of revision surgery and implant failure was relatively lower than those of extramedullary devices.

To identify risk factors for lower extremity lymphedema (LEL) using computed tomographic (CT) scan in patients undergoing lymphadenectomy for gynecologic cancers.We retrospectively reviewed 511 consecutive gynecologic cancer patients undergoing lymphadenectomy. Mean difference (3.77±3.14mm) of subcutaneous layer thicknesses between preoperative and postoperative 1-year CT scans of 106 patients with clinical LEL was used as an objective criterion for regrouping all the patients into those with mean difference3.77mm and ≤3.77mm. Risk factors for clinical LEL and significant increase of subcutaneous layer thickness on CT were evaluated using a logistic regression model.A total of 106 (20.7%) patients were clinically diagnosed with LEL by a physician. Total number of lymph nodes (LNs) retrieved30 (Odds ratio [OR] 3.2; 95% Confidence interval [CI] 1.94-5.32; p0.001) and adjuvant pelvic radiotherapy (OR 3.1; 95% CI 1.75-5.52; p0.001) were risk factors for clinical LEL. One hundred-nineteen (23.3%) had subcutaneous layer thickness increase of3.77mm. In addition to number of LNs retrieved30 (OR 2.3; 95% CI 1.40-3.74; p=0.001) and adjuvant pelvic radiotherapy (OR 1.7; 95% CI 1.01-2.74; p=0.046), open surgery (OR 1.8; 95% CI 1.01-3.11; p=0.045), long operation time (OR 1.7; 95% CI 1.05-2.83; p=0.032), and no use of intermittent pneumatic compression (IPC) (OR 2.1; 95% CI 1.06-4.16; p=0.034) were risk factors for thick subcutaneous layer on postoperative CT.In addition to high LN retrieval and adjuvant pelvic radiotherapy, open surgery, long operation time, and no IPC use could be risk factors for occult LEL after lymphadenectomy in gynecologic cancers.

On the basis of emerging data and the current understanding of minimally invasive surgery (MIS) for radical hysterectomy (RH) in women with cervical cancer, the Korean Society of Gynecologic Oncology, Korean Society of Obstetrics and Gynecology, and Korean Society of Gynecologic Endoscopy and Minimally Invasive Surgery support the following recommendations: • According to the recently published phase III Laparoscopic Approach to Cervical Cancer (LACC) trial—a prospective randomized clinical trial—disease-free survival and overall survival rates of MIS RH are significantly lower than those of open RH.• Gynecologic oncologists should be aware of the emerging data on MIS RH for early-stage cervical cancer.• The results of the LACC trial, together with institutional data, should be discussed with patients before choosing MIS RH.• MIS RH should be performed for optimal candidates according to the current practice guidelines by gynecologic oncologists who are skilled at performing MIS.

Objective To compare survival outcomes of primary laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in patients with FIGO stage IB cervical cancer. Methods We retrospectively identified stage IB1–IB2 cervical cancer patients who received either LRH (n = 343) or ORH (n = 222) at two tertiary institutional hospitals between 2000 and 2018. To adjust for confounders, we conducted Mahalanobis distance-based sample matching for stage, histology, cervical mass size, parametrial invasion, and lymph node metastasis. Then, survival outcomes were compared between the matched groups. Through the independent matching processes, we narrowed the study population to stage IB1 patients and stage IB1 patients with tumor size ≤2 cm on pre-operative MRI. Results After matching, LRH group showed poorer progression-free survival (PFS) than ORH group (3-year: 85.4% vs. 91.8%; P = 0.036), whereas no significant difference in overall survival (OS) was found. Regarding recurrence patterns, no significant differences in the incidences of pelvic, retroperitoneal lymph node and abdominal recurrences, or distant metastasis were observed between the two groups. Among the matched patients with stage IB1 who had cervical mass size ≤2 cm, the LRH and ORH groups showed similar PFS (3-year: 90.0% vs. 93.1%; P = 0.8) and OS (5-year: 98.6% vs. 96.4%; P = 0.6). Conclusions Despite the retrospective design, our matched cohort study suggests that ORH might be preferable for the surgical treatment of FIGO stage IB cervical cancer. However, in stage IB1 patients with tumor size ≤2 cm, LRH might be applicable, as equivalent outcomes were found regardless of the surgical approach. Further prospective studies are warranted.

We compared two groups of early stage cervical cancer patients treated with different surgical methods without adjuvant treatment using retrospective multicenter data previously collected for Korean Gynecologic Oncology Group (KGOG) study designed for developing prognostic models.We initially assessed data from the multi-institutional cohort with early stage (IB-IIA) cervical cancer patients treated with radical hysterectomy without adjuvant treatment between 2000 and 2008. Propensity score matching was performed to compare disease-free survival (DFS) and overall survival (OS) of patients with laparoscopic to abdominal radical hysterectomy. Additionally, survival comparison was performed in patients with tumor size2 cm.After matching, 119 patients with laparoscopic radical hysterectomy were compared with 357 patients with abdominal radical hysterectomy (median follow-up of 63.9 months). Inferior DFS was observed in the laparoscopy group (HR 2.738 [95% CI 1.326-5.650], p = 0.005) with a significant difference in pelvic (HR 5.110 [95% CI 1.817-14.473], p 0.001) and hematogenous recurrence (HR 3.171 [95% CI 1.059-9.494], p = 0.03), but OS was not significantly different between two groups (p = 0.624). In subgroup analysis in the patient with tumor size2 cm (laparoscopy 62 vs. laparotomy 186, median follow-up of 69.1 months), laparoscopy was associated with lower rate of DFS (HR 12.987 [95% CI 1.451-116.244], p = 0.003), but no significant difference in OS was observed between groups. Regarding OS, number of events is lacking, and inferior DFS in the laparoscopy group may be compensated by better response to radiation therapy in pelvic recurrence.In this analysis, laparoscopic radical hysterectomy was associated with lower rates of DFS but not OS in early stage cervical cancer patients without adjuvant treatment. Further larger scale studies are needed.

The 34th Annual Meeting of Korean Society of Gynecologic Oncology (KSGO) was held in Busan, Korea from 26 to 27 April. Around 460 Korean and international clinicians gathered in Busan to share and discuss their latest work and key issues of gynecologic oncologic research and treatment. The scope of this meeting included recent clinical trials and updates in gynecologic oncology, advances in ovarian cancer treatment, targeted therapy and immunotherapy in gynecologic cancer, management of hereditary gynecologic cancer, and newly revised staging of cervical cancer. As expected, the ongoing debate regarding the recent clinical trial on minimally invasive surgery for early-stage cervical cancer was addressed throughout the congress and the initial outline of the KSGO position statement was open for discussion. The meeting was an opportunity for all participants to come together and explore scientific insights of gynecologic cancer.

Nineteen topics were selected as major clinical research advances in gynecologic oncology in 2018. For cervical cancer, the importance of human papillomavirus (HPV) testing alone as primary cervical cancer screening method and negative survival impact of minimally invasive surgery in early-stage cervical cancer were addressed. For ovarian cancer, cost-effectiveness of genetic testing to prevent cancer, use of analgesics and oral pill to reduce cancer risk, efficacy of secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, update in the use of poly (ADP-ribose) polymerase inhibitor, and efficacy of anti-angiogenic targeted treatments, including bevacizumab and tyrosine kinase inhibitors, were reviewed. For corpus cancer, sentinel lymph node mapping technique, adjuvant therapy in high-risk endometrial cancer (PORTEC-3), and targeted therapy in recurrent disease were covered. For the field of radiation oncology, survival outcomes of chemoradiation compared with chemotherapy alone in metastatic cervical cancer and new findings regarding the use of neoadjuvant chemotherapy in locally advanced cervical cancer were introduced. Lastly, for breast cancer, the use of talazoparib in patients with germline BRCA1/2 mutation, ovarian suppression for premenopausal patients, adjuvant chemotherapy guided by 21-gene assay, and combination therapy of atezolizumab and nab-paclitaxel for triple-negative cancer as well as promising overall survival results of palbociclib and fulvestrant in advanced breast cancer were briefly mentioned.

OBJECTIVE To investigate the incidence and trends of cervical (C53), endometrial (C54.1), and ovarian cancer (C56) among Korean females between 1999 and 2015. METHODS The incidence of the three major gynecological cancers between 1999 and 2015 was analyzed based on the data from the Korea Central Cancer Registry. The age-standardized rates (ASRs) and the annual percent changes (APCs) for each site were calculated. RESULTS The absolute incidence rates of the three major gynecological cancers increased from 6,394 in 1999 to 8,288 in 2015. ASR for gynecologic cancer decreased from 23.7 per 100,000 in 1999 to 21.1 in 2015. This was mainly due to a definitive decrease in the incidence of cervical cancer, which recorded an APC of -3.7%. The trends of APC for gynecologic cancer were variable, being -1.36% between 1999 and 2006 and -0.11% between 2006 and 2015. A definitive but variable increase was noted for endometrial cancer, and the APC for this cancer was 7.4% between 1999 and 2009 and 3.5% between 2009 and 2015. The incidence of ovarian cancer gradually increased, with an APC of 1.8% between 1999 and 2015. CONCLUSION Overall, ASRs and APCs for the three major gynecological cancers are decreasing, with a recent reduction in the width of the change. However, there has been a progressive increase in the incidence of endometrial and ovarian cancers.

This study was performed to evaluate the anticancer effects of tolerable doses of metformin with or without medroxyprogesterone (MPA) in endometrial cancer cells. Cell viability, cell invasion, and levels of matrix metallopeptidase (MMP) and transforming growth factor (TGF)-&beta, 1 were analyzed using three human endometrial adenocarcinoma cell lines (Ishikawa, KLE, and uterine serous papillary cancer (USPC)) after treatment with different dose combinations of MPA and metformin. Combining metformin (0, 100, 1000 &micro, M) and 10 &micro, M MPA induced significantly decreased cell viability in a time- and dose-dependent manner in Ishikawa cells, but not in KLE and USPC cells. In KLE cells, metformin treatment alone significantly inhibited cell invasion in a dose-dependent manner. The inhibitory effect of metformin was reversed when 10 &micro, M MPA was combined, which was significantly inhibited again after treatment of MMP-2/9 inhibitor and/or TGF-&beta, inhibitor. Changes of MMP-9 and TGF-&beta, 1 according to combinations of MPA and metformin were similar to those of invasion in KLE cells. In conclusion, the anticancer effects of tolerable doses of metformin varied according to cell type and combinations with MPA. Anti-invasive effect of metformin in KLE cells was completely reversed by the addition of MPA, this might be associated with MMP-9 and TGF-&beta, 1.

Most patients with advanced-stage epithelial ovarian cancer will experience a relapse of disease despite a complete response after surgical cytoreduction and platinum-based chemotherapy. Treatment of recurrent ovarian cancer mainly comprises various combinations of systemic chemotherapy with or without targeted agents. The role of cytoreductive surgery for recurrent ovarian cancer is not well established. Although the literature on survival benefit of cytoreductive surgery for recurrent disease has expanded steadily over the past decade, most studies were retrospective, single-institution series with small numbers of patients. Given the balance between survival benefit and surgery-related morbidity during maximum cytoreductive surgical effort, it is essential to establish the optimal selection criteria for identifying appropriate candidates who will benefit from surgery without worsening quality of life. Three phase III randomized trials for this issue are currently underway. Herein, we present contemporary evidence supporting the positive role of cytoreductive surgery and offer selection criteria for optimal candidates for surgery in the treatment of recurrent ovarian cancer.

The hierarchically sea urchin-like structured reduced graphene oxide (RGO)-manganese dioxide (MnO2) nanocomposites have been assembled through an electrochemical deposition. MnO2 particles are uniformly grown and directly deposited onto the surface of three dimensional (3D) RGO. The crystalline phase, size and composition of MnO2 nanoparticles are γ phase, about 6 nm and 60 wt%, respectively. The specific capacitance of 125.93 F g−1 of 3D RGO-MnO2 composite is higher than 38.45 F g−1 of MnO2. The composite reveals the good rate capability of 70.29% and cyclic stability of ∼80% after 5000 cycles.

Objective Most interventions aimed at reducing bleeding during myomectomy lack sufficient evidence regarding their effectiveness. Recently, it was reported that intraoperative ascorbic acid administration effectively reduced blood loss during abdominal myomectomy. Therefore, this study aimed to investigate whether intravenous ascorbic acid infusion would affect intraoperative blood loss in women undergoing laparoscopic myomectomy. Study design A randomized, double-blind, parallel-group, placebo-controlled trial including 50 women undergoing laparoscopic myomectomy was conducted. Women with ≤4 myomas, ≤9 cm in maximum diameter were eligible. The study:control group ratio was 1:1. Starting 30 minutes before anesthesia, 2 g of ascorbic acid or a placebo were administered for 2 hours intraoperatively. Intraoperative blood loss, the primary endpoint, was calculated as the difference between the volume of fluids acquired from suction and that used for irrigation of the abdominal cavity during surgery using constant values. Results Among the 50 randomized women, 1 and 3 in the study and control groups, respectively, were excluded due to withdrawal of consent, cancelation of surgery, or non-measurement of the primary endpoint. The baseline and operative characteristics were similar between the study and control groups, as was the intraoperative blood loss (193 ± 204 mL vs. 159 ± 193 mL, P = 0.52). In addition, the operating time (95 ± 29 min vs. 110 ± 52 min; P = 0.50) and decrease in hemoglobin level after surgery (1.9 ± 1.31 g/dL vs. 1.4 ± 1.4 g/dL; P = 0.24) were similar between the study and control groups. Conclusions Intravenous ascorbic acid infusion did not reduce intraoperative blood loss in women undergoing laparoscopic myomectomy. Clinical trial registration ClinicalTrials.gov, www.clinicaltrials.gov , NCT01715597 .

Purpose We compared the predictive and prognostic values of leukocyte differential counts, systemic inflammatory (SIR) markers and cancer antigen 125 (CA-125) levels, and identified the most useful marker in patients with ovarian clear cell carcinoma (OCCC). Materials and Methods The study included 109 patients with OCCC who did not have any inflammatory conditions except endometriosis, and underwent primary debulking surgery between 1997 and 2012. Leukocyte differential counts (neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet), SIR markers including neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR), and CA-125 levels were estimated to select potential markers for clinical outcomes. Results Among potential markers (neutrophil, monocyte, platelet, NLR, MLR, PLR, and CA-125 levels) selected by stepwise comparison, CA-125 levels were best at predicting advanced stage disease, suboptimal debulking and platinum-resistance (cut-off values, ≥ 46.5, ≥ 11.45, and ≥ 66.4 U/mL; accuracies, 69.4%, 78.7%, and 68.5%) while PLR ≥ 205.4 predicted non-complete response (CR; accuracy, 71.6%) most accurately. Moreover, PLR < 205.4 was an independent factor for the reduced risk of non-CR (adjusted odds ratio, 0.17; 95% confidence interval [CI], 0.04 to 0.69), and NLR < 2.8 was a favorable factor for improved progression-free survival (PFS; adjusted hazard ratio, 0.49; 95% CI, 0.25 to 0.99) despite lack of a marker for overall survival among the potential markers. Conclusion CA-125 levels may be the most useful marker for predicting advanced-stage disease. Suboptimal debulking and platinum-resistance, and PLR and NLR may be most effective to predict non-CR and PFS in patients with OCCC.

Background Bmi1, a polycomb group gene, is essential for self-renewal of stem cells and is frequently upregulated in various cancer cells. We aimed to investigate the effect of Bmi1 silencing on cancer stemness and chemosensitivity in endometrial cancer using targeted siRNA approach in HEC1A and Ishikawa cells. Methods Cell viability after treatment with Bmi1 siRNA was assessed using the MTT assay, and cell apoptosis was visualized using the TdT-mediated dUTP nick-end labeling (TUNEL) method. Western blotting, migration assays and invasion assays were performed to detect changes in the stem-like properties of cancer cells. To evaluate the anticancer effect of Bmi1 silencing, HEC1A and Ishikawa cells were treated with 100 nM Bmi1 siRNA and/or 40 μM cisplatin. Results In the MTT assay, compared to control, viability of HEC1A and Ishikawa cells significantly decreased after Bmi1 siRNA treatment in a dose-dependent manner. Bmi1 silencing using siRNA increased the expression of cleaved caspase-3 and cleaved poly adenosine diphosphate-ribose polymerase polymerase (PARP) as observed in the western blot analysis. Apoptosis significantly increased in the HEC1A and Ishikawa cells treated with 100 nM Bmi1 siRNA for 48 h than in the control cells in TUNEL assay. SOX2 and Oct4 expression decreased in the HEC1A and Ishikawa cells treated with Bmi1 siRNA, while E-cadherin expression increased. Further, migratory and invasive properties were significantly inhibited by Bmi1 siRNA treatment in both cell lines. Notably, viability of HEC1A and Ishikawa cells decreased more when they were concurrently treated with Bmi1 siRNA and cisplatin compared to when they were treated with Bmi1 siRNA or cisplatin alone. Conclusion Bmi1 silencing suppresses cancer stemness in HEC1A and Ishikawa cells. Concurrent treatment with Bmi1 siRNA and cisplatin resulted in additive anticancer effect with a cell line-specific pattern, which was higher than that shown by cisplatin treatment alone.

Evidence has shown that multidisciplinary tumor board conferences (MTBCs) improve patient management for various cancer types. However, few retrospective studies have investigated MTBC efficacy for patients with gynecologic cancers. Here, we prospectively aimed to evaluate how MTBCs influence patient management in gynecologic oncology. This prospective study included 85 consecutive cases that were presented at gynecologic oncology MTBCs in our tertiary university hospital between January 2015 and April 2016. The primary endpoint was treatment plan change rate, which included both major and minor changes. Major changes were defined as exchange, addition, or subtraction of treatment modality. Minor changes included all other, such as intramodality changes or treatment time changes. The secondary endpoints were the change rates of diagnosis, diagnostic work-up, and radiological and pathological findings. The treatment plan change rate, irrespective of changes in diagnostic work-up, was 27.1%, which included 10.6% major and 16.5% minor changes. Among the treatment plan changes, changes in the treatment plan change rate alone were noted in 16.5% of cases, and changes in diagnosis and radiological findings occurred in 7.1% and 3.5% of cases, respectively. Diagnosis and radiological findings, irrespective of changes in diagnostic work-up, were also changed in 9.4% and 10.6% of cases, respectively. However, there were no changes in pathological findings. Moreover, there was a change of diagnostic method for further work-up in 23.5% of cases. The implementation rate of MTBC-determined treatment changes was 91.8%. Gynecologic oncology MTBCs resulted in considerable changes in treatment plans. Diagnosis, diagnostic work-up, and radiological findings were influenced by MTBCs. The data emphasize the importance of adopting a multidisciplinary team approach for gynecologic cancer management.