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PURPOSE Here, we compared the operative and perioperative outcomes between robot-assisted laparoscopic myomectomy (RALM) and abdominal myomectomy (AM) in patients with large (>10 cm) or heavy myomas (>250 g). MATERIALS AND METHODS We included 278 patients who underwent multi-port RALM (n=126) or AM (n=151) for large or heavy myomas in a tertiary care hospital between April 2019 and June 2020. The t-test, chi-square, Bonferroni's test, and multiple linear regression were used. RESULTS No differences were observed in age, body mass index, parity, or history of pelvic surgery between the two groups. Myoma diameters were not different (10.8±2.52 cm vs. 11.2±3.0 cm, p=0.233), but myomas were lighter in the RALM group than in the AM group (444.6±283.14 g vs. 604.68±368.35 g, respectively, p=0.001). The RALM group had a higher proportion of subserosal myomas, fewer myomas, fewer large myomas over >3 cm, lighter myomas, and longer total operating time. However, the RALM group also had shorter hospital stay and fewer short-term complications. Estimated blood loss (EBL) was not different between the two groups. The number of removed myomas was the most significant factor (coefficient=10.89, p

Study Objective To investigate the prognostic factors and impact of minimally invasive surgery (MIS) in surgically treated early-stage high-grade (HG) neuroendocrine cervical carcinoma (NECC). Design Retrospective cohort study. Setting Asan Medical Center, Seoul, Korea. Patients Patients with International Federation of Obstetrics and Gynecology (2009) stages IB1 to IIA HG NECC. Interventions All patients underwent radical hysterectomy (RH) with a laparotomy or an MIS approach. Measurements and Main Results Between 1993 and 2017, 47 patients with International Federation of Obstetrics and Gynecology stages IB1 to IIA1 HG NECC were initially treated with RH. Clinicopathologic variables of patients were retrospectively reviewed from electronic medical records. The median follow-up period was 28.2 months (interquartile range, 17.1–42). Stage IB1 disease was the most common (70.2%). Twenty-nine patients (61.7%) underwent RH by MIS. The overall survival (OS) and disease-free survival (DFS) rates were 63.8% and 38.3%, respectively. Lymph node metastasis and resection margin involvement were significant risk factors for DFS (hazard ratio [HR], 2.227; 95% confidence interval [CI], 1.018–4.871; p =.045 and HR, 6.494; 95% CI, 1.415–29.809; p =.016, respectively) and OS (HR, 3.236; 95% CI, 1.188–8.815; p =.022 and HR, 12.710; 95% CI, 1.128–143.152; p =.040, respectively). The Kaplan-Meier survival curves revealed no significant differences in OS and DFS between the laparotomy and MIS groups (50% vs 72.4% log-rank p =.196, 38.9% vs 37.9% p =.975). Conclusion Lymph node metastasis and resection margin involvement were poor prognostic factors of survival outcomes in initially surgically treated early-stage HG NECC. No difference was observed in the survival outcomes between the MIS and laparotomy approaches.

본고는 한국의 민주화 과정에서 대중의 인식과 선호가 외교정책 결정 과정에 어떠한 영향을 끼치는지 살펴보았다. 특히 한국 민주주의에서 점점 뚜렷해지는 좌우 진영논리와 그로 인한 여론의 양분화와 정치화가 외교정책의 딜레마로 이어진 대표적인 세 가지 사례, 즉 i) 2008년 광우병 파동과 촛불시위로 인한 한미협상 결과; ii) 2015년 한일 ‘위안부합의’에 대한 여론의 반대와 그 결과; 그리고 iii) 2017년 THAAD 배치와 그에 따른 중국과의 관계에 대한 상충되는 주장을 비교 고찰하였다. 이들 사례를 통해 살펴볼 수 있듯이, 극도로 정치화･양분화된 여론 및 잘못된 포퓰리즘에 기반한 전략은 국익을 최우선시 해야하는 한국 외교에 커다란 걸림돌이 되어왔다. 따라서 정치지도자는 국익에 근거한 엄격한 외교정책원칙을 준수하며 불안정하고 자칫 감정에 치우칠 수 있는 여론에 휘둘리지 않는 인지적 분별력과 강단이 필요하다. 이와 동시에 민주적 책임을 진 지도자는 국민의 일상에 지대한 영향을 미칠 외교정책을 결정하기 전에 시민사회와의 ‘건설적인’ 대화를 지속해야 한다. 대중적 또는 당파적 선호 때문에 쉽게 흔들리지 않는 책임감 있고, 반응하고, 합법적인 외교정책을 수립·이행하기 위해 정부는 여론을 존중하고 국민은 국익이 무엇인지 이해하고 우선시하는 상호 윈-윈(win-win) 접근이 중요하다.

There are few studies between postoperative neutrophil to lymphocyte ratio (NLR) and survival in cervical cancer. We compared postoperative changes in NLR according to surgical methods and analyzed the effect of these changes on 5-year mortality of cervical cancer patients. A total of 929 patients were assigned to either the laparoscopic radical hysterectomy (LRH) (n = 721) or open radical hysterectomy (ORH) (n = 208) group. Propensity score matching analysis compared the postoperative NLR changes between the two groups, and multivariate logistic regression analysis evaluated the association between NLR changes and 5-year mortality. Surgical outcomes between the two groups were also compared. In the LRH group, NLR changes at postoperative day (POD) 0 and POD 1 were significantly lower than in the ORH group after matching (NLR change at POD 0, 10.4 vs. 14.3, p &lt, 0.001, NLR change at POD 1, 3.5 vs. 5.4, p &lt, 0.001). In multivariate logistic regression analysis, postoperative NLR change was not associated with 5-year mortality (2nd quartile: OR 1.55, 95% CI 0.56–4.29, p = 0.401, 3rd quartile: OR 0.90, 95% CI 0.29–2.82, p = 0.869, 4th quartile: OR 1.40, 95% CI 0.48–3.61, p = 0.598), whereas preoperative NLR was associated with 5-year mortality (OR 1.23, 95% CI 1.06–1.43, p = 0.005). After matching, there were no significant differences in surgical outcomes between the two groups. There were significantly fewer postoperative changes of NLR in the LRH group. However, the extent of these NLR changes was not associated with 5-year mortality. By contrast, preoperative NLR was associated with 5-year mortality.

Immunoprofiling has an established impact on the prognosis of several cancers, however, its role and definition in high-grade serous ovarian cancer (HGSOC) are mostly unknown. This study is to investigate immunoprofiling which could be a prognostic factor in HGSOC. We produced tumor microarrays of 187 patients diagnosed with HGSOC. We performed a multiplexed immunofluorescence staining using Opal Multiplex IHC kit and quantitative analysis with Vectra-Inform system. The expression intensities of programmed death-ligand 1 (PD-L1), CD4, CD8, CD20, FoxP3, and CK in whole tumor tissues were evaluated. The enrolled patients showed general characteristics, mostly FIGO stage III/IV and responsive to chemotherapy. Each immune marker showed diverse positive densities, and each tumor sample represented its immune characteristics as an inflamed tumor or noninflamed tumor. No marker was associated with survival as a single one. Interestingly, high ratios of CD8 to FoxP3 and CD8 to PD-L1 were related to the favorable overall survival (77 vs. 39 months, 84 vs. 47 months, respectively), and CD8 to PD-L1 ratio was also a significant prognostic factor (HR 0.621, 95% CI 0.420–0.917, p = 0.017) along with well-known clinical prognostic factors. Additionally, CD8 to PD-L1 ratio was found to be higher in the chemosensitive group (p = 0.034). In conclusion, the relative expression levels of CD8, FoxP3, and PD-L1 were significantly related to the clinical outcome of patients with HGSOC, which could be a kind of significant immunoprofiling of ovarian cancer patients to apply for treatment.

We aimed to compare the perioperative outcomes of single-incision robotic myomectomy (SIRM) and multiport robotic myomectomy (MPRM) and provide surgical tips. We retrospectively analyzed the medical records of 462 patients with symptomatic leiomyoma who underwent MPRM or SIRM between March 2019 and April 2021. Demographic characteristics and surgical outcomes, including the&nbsp, total operative time (OT), estimated blood loss (EBL), and surgical complication rate, were compared between the two groups. Patients in the SIRM group had lower a body mass index and rate of previous pelvic surgery and were younger than those in the MPRM group. The myoma type was not different between groups, however, the MPRM group had larger, and more myomas than the SIRM group. After propensity score matching, these variables were not significantly different between the groups. The total OT, EBL, difference in hemoglobin levels, transfusion rate, and postoperative fever were not different between the groups. No postoperative complications occurred in the SIRM group. In the MPRM group, one patient needed conversion to laparotomy, and two patients had postoperative complications (umbilical incisional hernia and acute kidney injury). In conclusion, both MPRM and SIRM are feasible and effective surgical options for symptomatic myomas with cosmetic benefits and minimal risk of laparotomy conversion.

Objective To assess the clinical usefulness and diagnostic accuracy of ultrasonographic measurement of endometrial thickness (ET) in women with endometrial hyperplasia or cancer (EH+). Methods This retrospective cohort study included 29,995 consecutive women who underwent transvaginal ultrasonography (TVS) for an incidental finding of a thickened endometrium at the health screening and promotion center at Asan Medical Center between 2006 and 2010. Among 959 patients with endometrial abnormalities, 92 patients were included in this study. A total of 867 patients were excluded: 416 were lost to follow-up; 263 did not undergo endometrial biopsy; 155 had endometrial polyps; 17 had submucosal myomas; and 16 had insufficient tissue samples. Endometrial histology was the reference standard for calculating accuracy. Results Of the 92 patients, 78 (84.8%) had normal pathology, while 14 (15.2%) had endometrial pathology (EH+), including 5 patients (35.7%) with simple hyperplasia without atypia, 3 (21.4%) with complex hyperplasia, and 6 (42.9%) with endometrial carcinoma, all stage Ia. The area under the receiver-operating characteristic curve was 0.75 (95% confidence interval [CI], 0.593-0.906). The cut-off value for ET was 8 mm, indicating that TVS ET had a fair accuracy in diagnosing carcinoma, had a sensitivity of 100% (95% CI, 62.9-100.0%) and a specificity of 24.3% (95% CI, 15.2-36.3%). Conclusion TVS is useful for detecting EH+, with a cut-off value for ET of 8 mm having a high sensitivity for detecting endometrial pathologies and the ability to identify women highly unlikely to have EH+, thereby avoiding more invasive endometrial biopsy.

Background We aimed to review the burden and the potential impact of human papillomavirus (HPV) vaccines on HPV-related diseases in the Republic of Korea and to discuss cervical cancer prevention practices in this country. Methods Cancer burden statistics were retrieved from GLOBOCAN-2018 and Statistics Korea. HPV disease burden was assessed via systematic review. Vaccine types relative contribution (RC) was estimated using data from an international project using formalin-fixed paraffin-embedded specimens. Results Despite a downtrend in cervical cancer in recent years, Korean rates remain high. In contrast, oropharyngeal cancer incidence has gradually increased and other anogenital cancers remain rare. In Korea, HPV prevalence in general population is around 20%. In cervical cancer, RC of HPVs 16/18 (74.0%) increased to 92.0% when including HPVs 31/33/45/52/58. Limited information was available for other HPV-related cancer sites. Regarding prevention, since the inclusion of the HPV vaccine into the National Immunization Program, almost half (49%) of the target cohort in 2016 had received the first dose of vaccine. Further, percentage of women screened with pap has increased from 41.1%-2009 to 53.0%-2016. Conclusions HPV-related disease burden in Korea is significant. Results suggest that the combination of effective and high coverage HPV vaccination and screening programmes could substantially impact on HPV-related disease in Korea., Highlights • HPV-related disease burden (cancer and genital warts) in Korea is significant. • HPV16 is the most frequent genotype, causing itself more than 60% of HPV-related cancers. • HPV vaccine types 16/18/31/33/45/52/58/6/11 cause 92.0% of cervical cancers. • HPV vaccines could significantly impact on the HPV-related disease burden.

Since the human papillomavirus (HPV) vaccine guidelines were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2011, 2016, and 2019, several recent studies on the efficacy and safety of HPV vaccines in middle-aged women and men have been reported. Furthermore, there has been an ongoing debate regarding the efficacy of the HPV vaccine in women with prior HPV infection or who have undergone conization for cervical intraepithelial neoplasia (CIN). We searched and reviewed studies on the efficacy and safety of the HPV vaccine in middle-aged women and men and the efficacy of the HPV vaccine in patients infected with HPV and those who underwent conization for CIN. The KSGO updated their guidelines based on the results of the studies included in this review.

We aimed to investigate the effectiveness of continuing medical therapy in patients who did not achieve complete response (CR) despite 9 months of progestin treatment. We also sought to determine the prognostic factors associated with achieving CR among these patients.We retrospectively analyzed 51 patients with presumed stage IA, grade 1 or 2 endometrioid adenocarcinoma who had persistent disease on biopsy performed at 9-12 months after at least 9 months of progestin-based therapy. Data on clinicopathological factors and oncological and obstetrical outcomes following continuous hormonal treatment were extracted from the patients' medical records and analyzed. Univariate and multivariate analyses for predicting CR were performed.Thirty-seven (72.5%) of 51 patients achieved CR after prolonged fertility-sparing treatment. Median time to CR from starting initial progestin was 17.3 months (range, 12.1-91.7 months). On univariate analysis, history of polycystic ovarian syndrome, histologic grade 2, and not achieving partial response (PR) until 12 months were significantly associated with failure to CR (odds ratio [OR], 6.188, 95% confidence interval [CI], 1.405-27.244, p = 0.018; OR, 9.722, 95% CI, 1.614-58.581, p = 0.013; and OR, 21.750, 95% CI, 4.016-117.783, p 0.001, respectively). Multivariate analysis revealed that not achieving PR until 12 months was an independent prognostic factor predicting failure to CR after prolonged progestin therapy (OR, 21.803, 95% CI, 3.601-132.025, p = 0.001).Continued medical treatment is effective for persistent early endometrial carcinoma after at least 9 months of progestin therapy in young women who want to preserve their fertility.

Background Distant metastasis occasionally occurs in patients who have been diagnosed with colorectal cancer (CRC), but it occurs in a few patients with stage I CRC. The vagina as a metastasis site has also been reported, albeit rarely. Most reported cases of vaginal metastasis (VM) report their origin from advanced CRC. We encountered a patient who was diagnosed with isolated VM originating from stage I colon cancer (T2N0) and herein present the case of this patient. Case summary A 63-year-old woman visited the outpatient clinic because of a positive result from a stool occult blood test. She underwent laparoscopic anterior resection and was pathologically diagnosed with stage I (T2N0) sigmoid colon cancer. Neither lymphovascular invasion nor perineural invasion was observed. Ten months following the surgery, isolated vaginal metastases were detected on gynecologic examination. The examination was performed due to vaginal spotting. A transvaginal wide excision was performed, and no other adjuvant treatment was provided after discussion with a multidisciplinary team and the patient. Subsequently, a new VM was discovered after 33 mo. An additional transvaginal excision was performed. To date, there has been no evidence of further disease progression. From the time of diagnosis of VM, the patient's overall survival has been 54 mo. Conclusion VM can occur as a result of early-stage colorectal cancer. Surgeons should consider the possibility of VM following complaints of gynecologic symptoms following surgery.

Objective Circulating cell-free tumor DNA (cfDNA) is the DNA released by apoptotic and necrotic cells of the primary tumor into the blood during the period of tumor development. The cfDNA reflects the genetic and epigenetic alterations of the original tumor. TP53 mutations are a defining feature of high-grade serous ovarian carcinoma. We optimized the methods for detecting TP53 mutations in cfDNA from blood samples. We confirmed the correlation of TP53 mutation in primary ovarian cancer tissue and it in cfDNA using digital polymerase chain reaction (dPCR). Methods We found 12 frequent mutation sites in TP53 using The Cancer Genome Atlas and Catalogue of Somatic Mutations in Cancer data and manufactured 12 primers. The mutations in tissues were evaluated in fresh-frozen tissue (FFT) and formalin-fixed paraffin-embedded tissue (FFPET). We performed a prospective analysis of serial plasma samples collected from 4 patients before debulking surgery. We extracted cfDNA and calculated its concentration in blood. dPCR was used to analyze TP53 mutations in cfDNA, and we compared TP53 mutations in ovarian cancer tissue with those in cfDNA. Results Ten primers out of 12 detected the presence of TP53 mutations in FFT, FFPET, and cfDNA. In FFT and FFPET tissue, there were no significant differences. The average cfDNA concentration was 2.12±0.59 ng/mL. We also confirmed that mutations of cfDNA and those of FFT were all in R282W site. Conclusion This study developed detection methods for TP53 mutations in cfDNA in ovarian cancer patients using dPCR. The results demonstrated that there are the same TP53 mutations in both ovarian cancer tissue and cfDNA.

Purpose Genexol-PM is a biodegradable cremophor EL-free polymeric micelle formulation of paclitaxel. Here,we compared efficacy and safety of Genexol-PM plus carboplatin versus Genexol plus carboplatin for ovarian cancer treatment. Materials and methods In this multicenter, randomized, phase II study, patients with International Federation of Gynecology and Obstetrics IC-IV epithelial ovarian cancer were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 with 5 area under the curve carboplatin every 3weeks (6 cycles). The primary endpointwas the carbohydrate antigen 125 and Response Evaluation Criteria In Solid Tumor composite overall response rate (ORR). Results Of 131 enrolled patients, 98 were included in intention-to-treat analysis. Mean dosages were 260.00±0.00 mg/m2 Genexol-PM or 174.24±3.81 mg/m2 Genexol. Median followup was 18.0 months (range, 6.1 to 33.8 months). ORR was 88.0% (95% confidence interval [CI], 80.4 to 95.6) with Genexol-PM, and 77.1% (95% CI, 67.1 to 87.1) with Genexol (noninferiority threshold, 16.3%). Median time to progression was 14.8 months (95% CI, 11.3 to 20.2) with Genexol-PM and 15.4 months (95% CI, 13.2 to 29.6) with Genexol (p=0.550). Overall, six patients died. Neutropenia was the most common toxicity (incidences of 86.0% vs. 77.1%, p=0.120). Peripheral neuropathy incidences were 84.0% versus 64.6% (p= 0.148). Peripheral neuropathy of ≥ grade 3 occurred in one patient receiving Genexol. All toxicities were manageable. Conclusion Genexol-PM plus carboplatin as first-line treatment in patients with epithelial ovarian cancer demonstrated non-inferior efficacy and well-tolerated toxicities compared with the standard paclitaxel regimen. Further studies are warranted to optimize the dose and schedule, and to investigate long-term outcomes.

Objective The study aims to identify preoperative predictors of complete cytoreduction and early recurrence and death in epithelial ovarian, tubal, and peritoneal cancer after neoadjuvant chemotherapy (NACT). Methods We performed a retrospective analysis of 85 patients who underwent 3 cycles of NACT. Patients were divided into 2 groups according to residual tumor at interval debulking surgery (IDS), and clinicopathologic, surgical, and follow-up data were compared. Results Cancer antigen 125 (CA-125) levels before the IDS after completion of NACT were higher in the residual tumor group (42.0 vs 116.6 U/mL, P = 0.006). The drop rate of CA-125 after NACT was higher in the no residual tumor group (96.8% vs 89.9%, P = 0.001). Patients with residual tumor showed lower disease-free and overall survival outcomes than patients with no residual tumor. In univariate analysis, CA-125 of 100 U/mL or less before IDS and a drop rate after NACT greater than 80% were preoperative predictive factors for complete cytoreduction. In multivariate analysis, a drop rate of CA-125 after NACT greater than 80% was an independent preoperative predictive factor for complete cytoreduction (P = 0.002). Progressive disease on follow-up image during NACT was an independent preoperative predictive factor for early recurrence and death (P Conclusions A significant drop of CA-125 after NACT and progressive disease on follow-up image are independent preoperative predictors for complete cytoreduction and early recurrence and death.

Objective To identify risk factors for distant recurrence in node-positive cervical cancer patients who underwent radical hysterectomy and pelvic lymph node dissection (PLND) with para-aortic lymph node sampling (PALNS) or para-aortic lymph node dissection (PALND). Methods A total of 299 patients in whom lymph node metastasis was confirmed after radical surgery at Asan Medical Center for stage IA2 to IIB cervical cancer from February 2001 to December 2012 were identified. In all, 72 (24.1%) patients underwent PLND only and 227 (75.9%) underwent PLND with PALNS or PALND. Four patients were excluded due to diagnosed with small cell carcinoma. The clinicopathologic data of 223 patients were retrospectively analyzed. Distant recurrence was defined as recurrence at a site over the pelvic radiation field. Results Among all 223 study patients, the mean number of positive lymph nodes was 4.46. There were 54 (24.2%) patients with distant metastasis. Multivariate analyses using the Cox proportional hazards model showed that histologic types (HR=3.031, P ≤0.001 for adenocarcinoma, HR=2.302, P =0.066 for adenosquamous carcinoma), number of positive lymph nodes (HR=1.077, P ≤0.001), and surgical stage (HR=1.264, P =0.022) were independent risk factors for distant recurrence of cervical cancer. A scoring system for the prediction of distant recurrence was generated by incorporating these factors and showed good discrimination and calibration (concordance index of 0.753). In an internal validation set, this scoring system showed good discrimination with a C-statistics of 0.777. According to the Hosmer-Lemeshow test, the chi-square was 0.650 and the P -value was 0.723. Conclusions We have developed a robust scoring system that can predict the risk of distant recurrence in node-positive cervical cancer patients after radical operation. This scoring system was used to identify a group of patients who required systemic control of distant micrometastasis. This group of patients is an appropriate target for consolidation chemotherapy after concurrent chemoradiation therapy.

The clinical utility of BRCA1/2 genotyping was recently extended from the selection of subjects at high risk for hereditary breast and ovary cancer to the identification of candidates for poly (ADP-ribose) polymerase (PARP) inhibitor treatment. This underscores the importance of accurate interpretation of BRCA1/2 genetic variants and of reducing the number of variants of uncertain significance (VUSs). Two recent studies by Findlay et al. and Starita et al. introduced high-throughput functional assays, and proactively analyzed variants in specific regions regardless of whether they had been previously observed. We retrospectively reviewed all BRCA1 and BRCA2 germline genetic test reports from patients with breast or ovarian cancer examined at Asan Medical Center (Seoul, Korea) between September 2011 and December 2018. Variants were assigned pathogenic or benign strong evidence codes according to the functional classification and were reclassified according to the ACMG/AMP 2015 guidelines. Among 3684 patients with available BRCA1 and BRCA2 germline genetic test reports, 429 unique variants (181 from BRCA1) were identified. Of 34 BRCA1 variants intersecting with the data reported by Findlay et al., three missense single-nucleotide variants from four patients (0.11%, 4/3684) were reclassified from VUSs to likely pathogenic variants. Four variants scored as functional were reclassified into benign or likely benign variants. Three variants that overlapped with the data reported by Starita et al. could not be reclassified. In conclusion, proactive high-throughput functional study data are useful for the reclassification of clinically observed VUSs. Integrating additional evidence, including functional assay results, may help reduce the number of VUSs.

This study was designed to analyze urinary proteins associated with ovarian cancer (OC) and investigate the potential urinary biomarker panel to predict malignancy in women with pelvic masses. We analyzed 23 biomarkers in urine samples obtained from 295 patients with pelvic masses scheduled for surgery. The concentration of urinary biomarkers was quantitatively assessed by the xMAP bead-based multiplexed immunoassay. To identify the performance of each biomarker in predicting cancer over benign tumors, we used a repeated leave-group-out cross-validation strategy. The prediction models using multimarkers were evaluated to develop a urinary ovarian cancer panel. After the exclusion of 12 borderline tumors, the urinary concentration of 17 biomarkers exhibited significant differences between 158 OCs and 125 benign tumors. Human epididymis protein 4 (HE4), vascular cell adhesion molecule (VCAM), and transthyretin (TTR) were the top three biomarkers representing a higher concentration in OC. HE4 demonstrated the highest performance in all samples with OC (mean area under the receiver operating characteristic curve (AUC) 0.822, 95% CI: 0.772&ndash, 0.869), whereas TTR showed the highest efficacy in early-stage OC (AUC 0.789, 95% CI: 0.714&ndash, 0.856). Overall, HE4 was the most informative biomarker, followed by creatinine, carcinoembryonic antigen (CEA), neural cell adhesion molecule (NCAM), and TTR using the least absolute shrinkage and selection operator (LASSO) regression models. A multimarker panel consisting of HE4, creatinine, CEA, and TTR presented the best performance with 93.7% sensitivity (SN) at 70.6% specificity (SP) to predict OC over the benign tumor. This panel performed well regardless of disease status and demonstrated an improved performance by including menopausal status. In conclusion, the urinary biomarker panel with HE4, creatinine, CEA, and TTR provided promising efficacy in predicting OC over benign tumors in women with pelvic masses. It was also a non-invasive and easily available diagnostic tool.

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.

In 2016, 9-valent human papillomavirus (HPV) vaccine has been newly introduced in Korea, thus the need to develop recommendations for the vaccine has raised. Until we decide to develop a guideline, no further studies on the bi-valent or quadri-valent HPV vaccine have been announced. We searched and reviewed the literatures focused on the efficacy of 9-valent HPV vaccine, the ideal age of 3-dose schedule vaccination, the efficacy of 9-valent HPV vaccine in middle-aged women, the efficacy of the 2-dose schedule vaccination, the safety of 9-valent HPV vaccine, the possibility of additional 9-valent HPV vaccination, and cross-vaccination of 9-valent HPV vaccine. So, Korean Society of Gynecologic Oncology (KSGO) developed a guideline only for 9-valent HPV vaccine.

Robot-assisted laparoscopic myomectomy (RALM) has broadened the indications even in com-plex myomas. However, the high cost of RALM remains the main disadvantage. Therefore, a surgical technique that can reduce the cost of RALM and still has the advantages of robotic sur-gery is required. We propose a “locking suture on myoma (LSOM)” technique and compared the operative and perioperative outcomes of patients who underwent RALM with or without the LSOM technique. We included 337 patients who underwent RALM with (n = 160) or without (n = 177) the LSOM technique between March 2019 and August 2020. The LSOM group had low parity and gravidity, with a low rate of Cesarean sections. Myoma type was not different between the groups, however, patients in the LSOM group had larger, heavier, and higher number of myo-mas, although fewer patients had multiple myomas and were discharged earlier. Total operating time, estimated blood loss, pre- and postoperative hemoglobin levels, transfusion rate, and postoperative fever were not different between the two groups. In conclusion, the LSOM tech-nique may be a viable surgical option for myomas, as it can reduce the cost of RALM by obviat-ing the need for robotic Tenaculum forceps.

Contrasting human security with national security, this chapter examines South Korea’s policies toward global refugees and North Korean defectors, an effective indicator of regime instability. It is argued that the security and welfare of individual persons, which are the very reason for the existence of a sovereign state, must be prioritized in human security practice. Policy development in this regard is essential for a middle-power nation. Some policy considerations are provided for the examination of refugee responses from the human security perspective, particularly regarding how to make stakeholder support more comprehensive and how to promote bottom-up engagement and empowerment.

Background Palliative chemotherapy should be used with caution when attempting to alleviate symptoms in patients with end-stage cancer. However, palliative chemotherapy continues to be utilized in cancer patients during their last stages of life. In this study, we analyzed the pattern of chemotherapy administered during the last 6 months of life in patients with end-stage gynecologic cancer who were treated with active palliative chemotherapy for the past 10 years. Method We retrospectively analyzed the data for patients with gynecologic cancer who died after undergoing active palliative chemotherapy without receiving hospice management at Asan Medical Center from 2006 to 2015. Patients were divided into two groups: those who died between 2006 and 2010, and those who died between 2011 and 2015. Based on the electronic medical records, the demographic and baseline characteristics of the patients, hospital admission during the last 6 months, invasive procedures, palliative chemotherapy patterns, and the time of the last chemotherapy session were confirmed. Results A total of 193 patients with gynecologic cancer were eligible for this study. 92 patients died during 2006 to 2010, and 101 patients died during 2011 to 2015. The mean frequency of admission during the last 6 months was 5.12 for those who died in 2006–2010 and 6.06 for those who died during 2011–2015 (p = 0.003); similarly, the mean frequency of palliative chemotherapy during the last 6 months was 3.84 (2006–2010) vs. 4.93 times (2011–2015; p

To compare the operative outcomes of patients undergoing either single-port or multiport laparoscopic hysterectomy (LH).Two hundred fifty-six women scheduled for LH for symptomatic myoma and/or adenomyosis from 8 tertiary teaching hospitals were randomized to single-port or multiport groups. Primary outcome was conversion and/or complication proportion of the planned procedure to determine whether the success proportion of the single-port approach was not inferior to that of the multiport approach. Secondary outcomes were postoperative pain and operative scar.Demographic parameters including age, body mass index, parity, and history of vaginal and cesarean delivery were comparable between the 2 groups. The primary outcome of a combined conversion and/or complication rate was similar between the single-port and multiport groups at 8% and 10.3%, respectively. Conversions were similar between the groups with 4% of single-port cases and .8% of multiport cases. Transfusions were the most frequent complication required in 4.0% of single-port cases and 7.9% of multiport cases, with no difference between the groups. Concerning secondary outcomes, postoperative pain score and patient and observer scar assessment were not different between the 2 groups. Although not a specific outcome measure, there was no difference between the groups in blood loss, operative time, and postoperative hospital stay.Single-port LH is not inferior to multiport LH in terms of conversion and/or complications rates, including transfusion. However, the single-port approach did not have any advantage over multiport LH with regard to pain or cosmetic outcomes. These findings were demonstrated by multi-institutional surgeons in Korea.

Objective Malignant Brenner tumors (MBTs) of the ovary are very rare, and their definition, biology, and treatment modality have not been established. This study investigated the clinical characteristics of MBTs and the importance of chemotherapy for recurrent disease. Materials and methods We conducted a retrospective analysis of 10 patients with MBT of the ovary treated at a single tertiary center from 1991 to 2013. Results The median age was 55.5 years (range, 37–68 years). Nine of the 10 patients were symptomatic. The median size of the ovarian tumors was 10.5 cm (range, 2.5–25.0 cm). The cancer antigen-125 level was elevated in three patients. Six patients had a stage I tumor, one had a stage II tumor, two had a stage III tumor, and one had a stage IV tumor. Six patients received systemic adjuvant chemotherapy after surgery. The mean follow-up duration was 54.5 months (range, 8–173 months). Disease recurrence occurred in four of the 10 patients. The median time to recurrence was 11 months (range, 9–18 months). Two patients with locoregional recurrence showed favorable results after chemotherapy, regardless of the initial stage of the tumor. The patient with the stage IIIC tumor is alive at 13 months after recurrence on current chemotherapy. The patient with the stage IV tumor showed no evidence of the disease > 12 years after the last chemotherapy. Lastly, two patients with distant recurrence died after showing a long-term survival of 49 months and 88 months, respectively, after recurrence and intensive chemotherapy. Conclusion Our results showed that systemic chemotherapy is beneficial in patients with recurrence of a primary MBT of the ovary, especially in the locoregional recurrence.

ObjectiveThe purpose of this study was to identify preoperative clinicopathological predictive factors for lymph node (LN) metastasis in women diagnosed with uterine papillary serous carcinoma (UPSC).MethodsWomen diagnosed with UPSC in our institution from 1997 to 2012 were identified. All patients underwent hysterectomy and bilateral salpingo-oophorectomy plus pelvic and/or para-aortic lymphadenectomy. The predictive values of the risk factors for LN metastasis were analyzed using χ2 and multivariate logistic regression analyses.ResultsA total of 94 patients met our study criteria. A CA-125 cutoff of 47.5 IU/mL on the receiver operating characteristic curve provided the best sensitivity and specificity (56.5% vs 90.1%, respectively) for LN metastasis prediction. The sensitivities and specificities of old age (≥60 years), body mass index of 25 kg/m2 or greater, deep myometrial invasion, tumor size greater than 2 cm, tumor size greater than 4 cm, preoperative CA-125 greater than 47.5 IU/mL, LN metastasis on imaging, and extrauterine spread on imaging for the presence of a positive LN were 39.1%, 34.8%, 30.4%, 34.8%, 21.7%, 56.5%, 43.5%, and 52.2%, and 52.1%, 45.1%, 78.9%, 57.7%, 83.1%, 90.1%, 93.0%, and 90.1%, respectively. Preoperative CA-125 (P < 0.001), LN metastasis on preoperative imaging (P < 0.001), and extrauterine spread on preoperative imaging (P = 0.009) were risk factors for LN metastasis on univariate analysis. Multivariate analysis revealed that preoperative CA-125 (P = 0.001) was the only independent risk factor for LN metastasis.ConclusionsPreoperative CA-125 is a preoperative predictive factor for LN metastasis in UPSC.

Aims: We investigated the prognosis of patients with small-cell neuroendocrine carcinoma of the uterine cervix (SCNEC) in relation to treatment modalities. Methods: We retrospectively reviewed the medical records and pathological reports of 102 patients who were histologically diagnosed with SCNEC at 5 different institutes. Time to progression (TTP) and overall survival (OS) were analyzed for each treatment modality. Results: Of the patients with early-stage [International Federation of Obstetrics and Gynecology (FIGO) stage IB2 or below] SCNEC, 57.8 and 79.3% underwent radical hysterectomy followed by adjuvant therapy. In advanced-stage SCNEC, concurrent chemoradiation therapy was given to 51.4% of the patients. The overall recurrence rate was 51.6%. In early- and advanced-stage SCNEC, the TTP was not different (22.3 vs. 13.3 months, p = 0.104), but the OS was different (40.7 vs. 21.4 months, p = 0.029). Parametrial involvement and lymph vascular space invasion were found to be associated with an unfavorable prognosis. Interestingly, survival was the most unfavorable in patients with early-stage SCNEC who had never received chemotherapy. FIGO stage and use of chemotherapy were identified as independent prognostic factors in SCNEC patients. Conclusions: SCNEC requires systemic chemotherapy as part of the initial treatment, along with surgery or radiation, even in patients with early-stage disease.

Clinical practice guidelines for gynecologic cancers have been developed by many organizations. Although these guidelines have much in common in terms of the practice of standard of care for uterine corpus cancer, practice guidelines that reflect the characteristics of patients and healthcare and insurance systems are needed for each country. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to produce the third edition of the guidelines as an advanced form based on evidence-based medicine, considering up-to-date clinical trials and abundant qualified Korean data. These guidelines cover screening, surgery, adjuvant treatment, and advanced and recurrent disease with respect to endometrial carcinoma and uterine sarcoma. The committee members and many gynecologic oncologists derived key questions from the discussion, and a number of relevant scientific literatures were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, together with other details. The objective of these practice guidelines is to establish standard policies on issues in clinical areas related to the management of uterine corpus cancer based on the findings in published papers to date and the consensus of experts as a KSGO Consensus Statement.

Objective This phase I study aimed to determine the maximum tolerated dose (MTD) of Genexol-PM, when combined with carboplatin, as a first-line treatment in patients with advanced ovarian cancer. Methods This open-label, multicenter, phase I, dose-escalation study included 18 patients (median age: 59.0 years, range: 40-75 years) diagnosed with advanced epithelial ovarian cancer. All patients had measurable residual disease after debulking surgery. Patients were assigned to groups (n=6 each group) that received different doses of Genexol-PM (220, 260, and 300 mg/m², once every 3 weeks) and 5 area under the curve (AUC) carboplatin. Safety and efficacy were analyzed for each dose group. Results In this intention-to-treat population, 3 out of 18 patients dropped out of the study: 1 due to dose-limiting toxicity (DLT), 1 due to hypersensitivity, and 1 was lost during follow-up. DLTs were not reported at 220 mg/m² or 260 mg/m², but at 300 mg/m², 1 patient experienced DLT (grade 3 general pain). The MTD of Genexol-PM was not determined, but a dose of 300 mg/m² or less could be recommended for the phase II study. Most patients (73.9%) with adverse events recovered without sequelae, and no death occurred that was related to the disease or treatment. The best overall response rate was 94.1%. Conclusion Genexol-PM combined with carboplatin was well tolerated as a first-line treatment, and good responses were observed in patients with advanced ovarian cancer. Based on these results, we recommended a dose of 300 mg/m² or less for a phase II study.

The Surgery Treatment Modality Committee of the Korean Gynecologic Oncologic Group (KGOG) has determined to develop a surgical manual to facilitate clinical trials and to improve communication between investigators by standardizing and precisely describing operating procedures. The literature on anatomic terminology, identification of surgical components, and surgical techniques were reviewed and discussed in depth to develop a surgical manual for gynecologic oncology. The surgical procedures provided here represent the minimum requirements for participating in a clinical trial. These procedures should be described in the operation record form, and the pathologic findings obtained from the procedures should be recorded in the pathologic report form. Here, we focused on radical hysterectomy and lymphadenectomy, and we developed a KGOG classification for those conditions.

Objective Most BRCA1/2 carriers do not undergo risk-reducing salpingo-oophorectomy (RRSO) by the recommended age. This study aimed to find the incidence of precursor lesions and cancer after RRSO. Methods We retrospectively reviewed breast cancer patients identified as BRCA mutation carriers who underwent RRSO at Asan Medical Center, Seoul, Korea, from 2010 to 2014. From 2013, all cases were examined according to the Sectioning and Extensively Examining the Fimbria (SEE/FIM) protocol and underwent immunohistochemically staining. RRSO was performed in 63 patients, 27 in 2010 to 2012 and 36 in 2013 to 2014. Results The median age at RRSO was 46.5 years (range, 32 to 73 years). Occult invasive cancer was detected in eight patients, of ovarian origin in five and of tubal origin in three. All occult invasive cancer cases with metastasis were detected in patients older than 40 years. Of the 36 patients from the 2013 to 2014 cohort, seven showed p53 overexpression, one showed Ki-67 overexpression, two showed serous tubal intraepithelial carcinoma, and three showed occult cancer. The detection rate of precursor lesions or cancer was 36.1% (13/36). In the analysis according to age, precursor lesions were more common in BRCA1 mutation carriers younger than 40 years old (66.7% vs. 20.0%). In BRCA2 mutation carriers, precursor lesions were only detected in those older than 40 years of age, indicating the possible faster occurrence of precursor lesions in BRCA1 mutation carriers. Conclusion Many patients still tend to delay RRSO until after they are 40 years old. Our findings support the significance of RRSO before the age of 40 in germline BRCA mutation carriers.

The purpose of this study was to evaluate the surgical feasibility of and survival outcome after laparoscopy in obese Korean women with endometrial cancer which has recently been increasing. We reviewed the medical records of the patients treated at our medical institution between 1999 and 2012. The patients were divided into three groups, non-obese (Body Mass Index [BMI]

The objective of this study was to assess whether the ratio of upper abdomen (UA) to lower abdomen (LA) (relative to the umbilicus) standardized fluorine 18 fluorodeoxyglucose uptake, as measured by preoperative positron emission tomography and computed tomography, is predictive of recurrence, survival, and suboptimal cytoreduction (residual tumor1.0 cm) in advanced-stage ovarian cancer (AOC).Positron emission tomography/computed tomography before surgical staging was performed in 159 AOC patients. The ratio between the highest maximum standardized uptake value (SUV(max)) in the UA and the LA was expressed as UA/LA SUV(max). Clinicopathological characteristics and follow-up information were collected retrospectively. Cox proportional hazards analysis was used to identify prognostic factors for recurrence and survival. Logistic regression analysis was used to identify predictors of suboptimal cytoreduction.The median age and follow-up period were 55 years (range, 27-80 years) and 32 months (range, 1-92 months), respectively; 133 and 26 patients had stage III and IV disease, respectively. There were 120 and 54 cases of recurrence and disease-specific death, respectively. Multivariate analysis showed that recurrence was associated significantly with high UA/LA SUV(max) (P0.05; hazard ratio [HR], 4.902; 95% confidence interval [CI], 2.521-9.531) and suboptimal cytoreduction (P0.05; HR, 2.431; 95% CI, 1.561-3.788), and that disease-specific death was significantly associated with high UA/LA SUV(max) (P0.05; HR, 2.777; 95% CI, 1.270-6.075), suboptimal cytoreduction (P0.05; HR, 1.951; 95% CI, 1.080-3.524), and histology (P0.05; HR, 4.134; 95% CI, 1.676-10.196). Upper abdomen/lower abdomen SUV(max) was the only independent predictor of suboptimal cytoreduction (P0.05; odds ratio, 4.644; 95% CI, 1.676-12.862).High preoperative UA/LA SUV(max) was significantly associated with poor prognosis and may be predictive of suboptimal cytoreduction in AOC. This parameter may be considered in the treatment of AOC patients.

Objective Laparoscopic management in patients with malignant nonepithelial ovarian tumors (MNEOTs) was unpopular owing to the solid nature and relatively large size of the tumors. The purpose of this study was to evaluate the role of laparoscopy for MNEOTs. Methods Between January 1989 and September 2010, 28 patients with MNEOTs underwent laparoscopic surgery at our institution. These patients’ clinicopathologic data were retrospectively reviewed from medical records. Results Cases included 20 sex cord–stromal tumors (18 granulosa cell and 2 Sertoli-Leydig cell) and 8 malignant germ cell tumors (4 dysgerminomas, 2 immature teratomas, 1 choriocarcinoma, and 1 yolk sac tumor). The patients’ median age was 27 years (range, 16–35 years) for those with malignant germ cell tumors and 42 years (range, 7–57 years) for those with stromal tumors. The median primary tumor diameter was 10.4 cm (range, 3.3–20.8 cm). Laparoscopic pelvic and para-aortic lymph node dissections were performed in 9 cases. Laparoscopic removal of primary tumor and omentectomy were performed in 26 and 6 cases, respectively. Hand-assisted laparoscopic surgery was performed for one huge tumor that could not be entered into the endobag. The median operating time was 102 minutes (range, 45–300 minutes), and the median postoperative hospital stay was 3 days (range, 2–10 days). All patients had stage I disease. Five patients received adjuvant chemotherapy, and the median interval to chemotherapy was 14 days (range, 2–21 days). No intraoperative complication or conversion to laparotomy was observed. Only one postoperative febrile morbidity occurred. The median follow-up was 34.5 months (1–185 months). One patient developed recurrence, which was treated with chemotherapy. No patient died of their disease. Conclusion This is the first case series report of laparoscopic surgery for MNEOTs. Laparoscopic management seems feasible and safe without compromising survival. With additional evidence, laparoscopic surgery could be a safe therapeutic option for management of early-stage MNEOTs.

Objective Concurrent chemoradiotherapy is usually administered to patients with locally advanced cervical cancer (LACC). Extended-field chemoradiotherapy is required if para-aortic lymph node (PALN) metastasis is detected. This study aimed to construct a prediction model for PALN metastasis in patients with LACC before definitive treatment. Methods Between 2009 and 2016, all consecutive patients with LACC who underwent para-aortic lymphadenectomy at two tertiary centers were retrospectively analyzed. A multivariate logistic model was constructed, from which a prediction model for PALN metastasis was developed and internally validated. Before analysis, risk grouping was predefined based on the likelihood ratio. Results In total, 245 patients satisfied the eligibility criteria. Thirty-four patients (13.9%) had pathologically proven PALN metastases. Additionally, 16/222 (7.2%) patients with negative PALNs on positron emission tomography/computed tomography (PET/CT) had PALN metastasis. Moreover, 11/105 (10.5%) patients with both negative PALNs and positive pelvic lymph nodes on PET/CT had PALN metastasis. Tumor size on magnetic resonance imaging and PALN status on PET/CT were independent predictors of PALN metastasis. The model incorporating these two predictors displayed good discrimination and calibration (bootstrap-corrected concordance index=0.886; 95% confidence interval=0.825–0.947). The model categorized 169 (69%), 52 (22%), and 23 (9%) patients into low-, intermediate-, and high-risk groups, respectively. The predicted probabilities of PALN metastasis for these groups were 2.9, 20.8, and 76.2%, respectively. Conclusion We constructed a robust model predicting PALN metastasis in patients with LACC that may improve clinical trial design and help clinicians determine whether nodal-staging surgery should be performed.

Background and Purpose: Ovarian cancer is the most frequent cause of death from gynecologic malignancy. Recently, immunotherapies have been suggested as ways to treat this malignancy. However, the ideal of immunotherapy has not been realized yet in ovarian cancer patients. Therefore, we investigated effects of monocyte-derived dendritic cells (mono DCs) and new-generation DCs subset (new DCs) on an ID8 orthotropic mouse model of ovarian cancer. Methods: Mono DCs were prepared from bone marrow of C57BL/6 mice. We isolated monocyte from bone marrow by monocyte isolation kit. Isolated monocyte was incubated for 7 days with IL-4 and GM-CSF. In addition, monocytes were pulsed with LPS and ID8 tumor lysate while incubating. Likewise new DCs were isolated from bone marrow of C57BL/6 mice. We isolated lineage negative cells from bone marrow using lineage cell depletion kit. Isolated cells were incubated with IL-4 and GM-CSF; also the cells were pulsed by ID8 tumor lysate and Rg3, which is a ginsenoside. Orthotropic model of ID8 was made on C57BL/6 mice. We injected 5x106 cells into peritoneal cavity. 4 weeks after cell injection, mice were grouped into three groups, which were vehicle, mono DCs and new DCs. Mice were injected with mono DCs and new DCs. 5x106 cells of DCs were injected 1 time/week for three weeks. One week later, mice were sacrificed and organs were harvested such as peritoneum, phren, ovary and tumor mass for histologic analysis. Results: DCs treated groups showed lower ascites formation than vehicle group. Ascites were fewest in new DCs group. Survival rate was lowest in vehicle group. Each survival rate is 0% in vehicle, 63% in new DCs and 80% in mono DCs. Also tumor growth at ovary was more decreased in mono DCs and new DCs group. In addition, mono DCs-treated mice showed low level of metastasis to other organs. Conclusion: Immunotherapy with dendritic cells showed inhibition of tumor growth and metastasis on mouse ovarian cancer. These results indicated that DCs treatments are able to be a potential therapy for ovarian cancer. It also could have synergy with the combined treatment of existing anticancer drugs. However, there are several limitations such as a relatively high dose of DCs and the procedure of isolating DCs needed large amount of bone marrow. We will continue to study and improve these issues. Citation Format: Min-Je Kim, Joo-won Kim, Ju-hyun Kim, Young-Jae Lee, Shin-Wha Lee, Yong-Man Kim. Immunotherapy with dendritic cells inhibited tumor growth on an ID8 orthotropic mouse model of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 119.

Background: The analysis of single parameters alone may not provide sufficient insights about complex immune system-tumor interactions. This study is to validate the immune contexture as prognostic biomarkers in high-grade serous ovarian cancer (HGS-OC) and to find new era of immunoscore in HGS-OC. Methods: We collected FFPE samples from 187 patients with HSOC and produced TMA samples. We accomplished the OPAL multiplex IHC assay for the quantitative analysis of immune markers, including CD4, CD8, CD20, FoxP3, PD-L1, and CK. Multiplex Biomarker Imaging and inForm® Image Analysis Software was used. Results: FIGO stage III and IV patients were 84.5% (158/187). The optimal debulking surgery was done in 66.8% (125/187). The 3-year disease-free survival and 5-year overall survival were 35.1% and 50.0%, respectively. Any single marker was not related to the survival, including CD8, FoxP3, and PD-L1. However, high CD8:FoxP3 and CD8:PD-L1 ratios were correlated with good survival. In Cox regression model, the risk factors for HGS-OC survival were FIGO stage (HR 1.784, 95% CI: 1.295-2.457, p Conclusion: These findings indicate that although any single immune marker is not related to the survival, CD8:FoxP3 and CD8:PD-L1 ratios provide the positive correlation with the prognosis in HGS-OC; especially, CD8:PD-L1 ratio is prognostic biomarker that is comparable to clinical biomarkers. The next study for immunoscore is necessary to define immunoscore in ovarian cancer. Citation Format: Shin-Wha Lee, Min-Je Kim, Ju-hyun Kim, Young-Jae Lee, Yong-Man Kim, Yong-Man Kim. Immunoscore as prognostic biomarkers in patients with epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5703.

Background: PARP inhibitors have demonstrated clinically meaningful increase in progression-free survival as a single agent in women with recurrent ovarian cancer following a response to platinum-based chemotherapy. However, there still needs more improvement in efficacy because PARP inhibitors have comparatively low efficacy in non-germline BRCA-mutated patients. We aimed to develop a novel PAPR inhibitor that may have potent antitumor efficacy against the non-germline BRCA-mutated patients in addition to the germline BRCA-mutated patients. Here, we describe a novel selective PARP inhibitor IDX-1197. Materials and Methods: We conducted in vitro assays to evaluate IDX-1197 as a PARP inhibitor using PARP enzyme assay and PARP-catalytic inhibition assay in Hela cells. We evaluated in vivo efficacy of IDX-1197 against ovarian and breast tumor growth using patient-derived xenograft models. To investigate PARP inhibition in tumors, tumor PAR levels were measured by ELISA in the PDX models. Results: In enzyme assay, IDX-1197 potently inhibited PARP1 and PARP2 activities with IC50 values of 1.4 nM and 1.0 nM, respectively. By contrast, IDX-1197 was not sensitive to PARP5A (Tankyrase-1), which belongs to the PARP family (IC50>10 μM). In DNA damage-induced Hela cells, IDX-1197 significantly inhibited PARP1-mediated PAR expression (EC50 = 0.5 nM). In the germline BRCA1-mutated ovarian cancer PDX model, oral administration of IDX-1197 exhibited significant PAR inhibition (>90%) in tumor tissues until 24 hr post dose. IDX-1197 also dose-dependently led to potent tumor growth inhibition compared to Olaparib treatment group. Furthermore, IDX-1197 showed improved antitumor activity against breast cancer PDX models, which included both germline BRCA-mutated and non-germline BRCA-mutated models. In these models, IDX-1197 exhibited greater tumor growth inhibition compared with olaparib and/or niraparib. Conclusions: IDX-1197 is a highly potent and selective inhibitor of PARP1/2 with significant in vitro and in vivo activities in multiple cancer models. These preclinical data demonstrate the efficacy of IDX-1197, which has the potential for a best-in-class profile, in non-germline BRCA-mutated patients as well as BRCA-mutated patients. Based on these findings, IDX-1197 has entered clinical phase 1 trial in Korea. Funded by National OncoVenture. Citation Format: Myongjae Lee, Joon-Tae Park, Ji-hun Yang, Dohee Kim, In-Gyu Je, Yoon Suk Lee, Jinah Jeong, Dong Keun Song, Soobong Park, Hong-Sub Lee, Yong-Man Kim, Shin-Wha Lee, Dong Woo Kang, Ha-Young Lee, Jung Yong Kim, Sungsook Lee, Nam Seok Baek, Jae-Hoon Kang. Development of IDX-1197, a novel, selective, and highly potent PARP inhibitor [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A106.

Objective. To investigate the efficacy of conization followed by conservative management for treating stage IA1 microinvasive carcinoma of the uterine cervix. Design/Setting. Retrospective study. Population. Seventy-five patients treated for stage IA1 microinvasive carcinoma of the cervix. Patients underwent conization followed by hysterectomy (Group 1, 53 patients), or were followed by conservative management (Group 2, 22 patients). Methods. Medical and histopathological record review. Results. For Group 1, pathology results showed that 30 had no residual tumor, one had cervical intraepithelial neoplasia (CIN) I, 11 had CIN III/cervical carcinoma in situ (CIS), nine had microinvasive carcinomas, and one had an invasive carcinoma (outcome for one patient not recorded). For Group 2, secondary procedures involved only cervical smears for 12 (48%) patients, of whom nine had normal cytology, one had low-grade squamous intraepithelial lesion and two had high-grade squamous intraepithelial lesions. For 13 (52%) patients in Group 2, secondary procedures involved repeat conization on whom six had no residual tumor, one had CIN II, four CIN III/CIS, and two microinvasive carcinoma and a negative resection margin. Therefore, conization followed by conservative management was an effective treatment for 90.9% (20/22) of Group 2. In neither group was recurrence recorded. There was no relation between lymphovascular invasion and follow-up cytology or pathology results, or between resection margin status and follow-up examination results. Conclusion. Conization alone with careful follow-up appears to be an effective and safe treatment for patients with stage IA1 microinvasive carcinoma of the uterine cervix, regardless of resection margins status or lymphovascular invasion.

Objective To evaluate the clinical role of adjuvant chemotherapy (AC) in FIGO stage IB-IIA cervical cancer patients. Study Design A cohort of 262 patients with cervical cancer who received radical hysterectomy (RH) and adjuvant therapy at Asan Medical Center between 1992 and 2012 was enrolled. In this cohort, 85 patients received adjuvant chemotherapy (AC), and 177 received adjuvant radiotherapy or concurrent chemoradiation therapy (AR). Oncologic outcomes and adverse events in both treatment arms were compared using weighted Cox proportional hazards regression models with inverse-probability-of-treatment weighting (IPTW) to reduce the impact of treatment selection bias and potential confounding factors. Results During a 46.8-month median follow-up duration, 39 patients (14.9%) had recurrences, and 18 patients (6.9%) died of disease. In multivariate analysis, the hazard ratio (HR) for recurrence and death was not significantly different in patients in either treatment arm (p=0.62 and 0.12, respectively). Also, after IPTW matching, the HR for recurrence did not significantly differ between the arms (HR 1.57, 95% CI 0.68-3.62, p=0.29). Similarly, disease-free survival and overall survival were not significantly different between the arms (p=0.47 and 0.13, respectively). In addition, patients with AC had a much lower prevalence of long-term complications (lymphedema: n=8 (9.4%) vs. 46 (26.0%), p=0.03; ureteral stricture: n=0 vs. 9 (6.2%), p=0.05). Conclusion Patients with FIGO stage IB-IIA cervical cancer can benefit from AC after RH with fewer long-term complications and non-inferior therapeutic effect to AR. Chemotherapy may therefore be an alternative adjuvant treatment option for cervical cancer, particularly in younger patients.

Congenital epulis is a benign intraoral tumor that has rarely been diagnosed prenatally. We report a fetus with congenital epulis diagnosed by three-dimensional (3-D) ultrasound and fetal magnetic resonance imaging (MRI) at 35 weeks' gestation. We show an image of congenital epulis using a new ultrasound technique, the 3-D multislice view, which shows images similar to CT or MRI. This is a short case report of congenital epulis diagnosed prenatally by 3-D ultrasound using multislice view and MRI.

Objective: Most BRCA1/2 carriers do not undergo risk-reducing salpingo-oophorectomy (RRSO) by the recommended age. This study aimed to find the incidence of precursor lesions and cancer after RRSO. Methods: We retrospectively reviewed breast cancer patients identified as BRCA mutation carriers who underwent RRSO at Asan Medical Center, Seoul, Korea, from 2010 to 2014. From 2013, all cases were examined according to the SEE/FIM protocol and underwent immunohistochemically (IHC) staining. RRSO was performed in 63 patients, 27 in 2010-2012 and 36 in 2013-2014. Results: The median age at RRSO was 46.5 years (32-73 years). Occult invasive cancer was detected in 8 patients, of ovarian origin in 5 and of tubal origin in 3. All occult invasive cancer cases with metastasis were detected in patients older than 40 years. Of the 36 patients from the 2013-2014 cohort, 7 showed p53 overexpression, 1 showed Ki-67 overexpression, 2 showed serous tubal intraepithelial carcinoma (STIC), and 3 showed occult cancer. The detection rate of precursor lesions or cancer was 36.1% (13/36). In the analysis according to age, precursor lesions were more common in BRCA1 mutation carriers younger than 40 years old (66.7% vs 20.0%). In BRCA2 mutation carriers, precursor lesions were only detected in those older than 40 years of age, indicating the possible faster occurrence of precursor lesions in BRCA1 mutation carriers. Conclusions: Many patients still tend to delay RRSO until after they are 40 years old. Our findings support the significance of RRSO before the age of 40 in germline BRCA mutation carriers. Citation Format: YoungJae Lee, YongMan Kim, ShinWha Lee. Pathologic findings at RRSO in germline BRCA mutation carriers with breast cancer: significance of bilateral RRSO at the optimal age in germline BRCA mutation carriers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 493. doi:10.1158/1538-7445.AM2017-493

e13046 Background: Most BRCA1/2 carriers do not undergo risk-reducing salpingo-oophorectomy (RRSO) by the recommended age of 40. Methods: We retrospectively reviewed breast cancer patients identified as BRCA mutation carriers who underwent RRSO at Asan Medical Center, Seoul, Korea, from 2013 to 2015. Both fallopian tubes of all cases were examined according to the SEE/FIM protocol and immunohistochemically (IHC) staining was performed when a precursor lesion was suspected. Results: RRSO was performed in 55 patients. The median age at RRSO was 44 years (32–73 years). Of the 36 patients with IHC staining, 7 showed p53 overexpression, 1 showed Ki-67 overexpression, 2 showed serous tubal intraepithelial carcinoma, 2 showed occult cancer, and 1 showed metastatic cancer of breast origin. All occult invasive cancer cases were tubal origin and detected in patients older than 40 years. The detection rate of premalignant lesions or cancer was 21.8% (12/55). Among patients who underwent RRSO under the age of 40, premalignant lesions were found only in BRCA 1 mutation carriers (40.0% vs 0%). In BRCA 2 mutation carriers, premalignant lesions were only detected in those older than 40 years of age, indicating the possible faster occurrence of premalignant lesions in BRCA1 mutation carriers. Conclusions: Many patients still tend to delay RRSO until after they are 40 years old. Our findings support the significance of RRSO before the age of 40 in germline BRCA mutation carriers, especially in BRCA 1 mutation carriers.

Supplemental Digital Content is available in the text, To identify prognostic factors for overall survival after recurrence (OSr) in endometrioid endometrial cancer (EC) patients and categorize patient subgroups that predict outcomes using these variables. Consecutive patients with recurrent endometrioid EC seen in our institution from 1989 to 2013 were retrospectively reviewed. Cox regression models were used to identify the clinicopathological factors associated with OSr. By summing scores proportionate to the hazard ratio (HR) for each significant variable, we stratified patients into 3 risk groups. Enrolled patients (n = 108) had a median time to recurrence of 15 (range, 3–163) months after initial treatment and a median OSr of 22 (range, 1–207) months. Twenty patients (18.5%) had locoregional recurrence, and 88 (81.5%) distant. One hundred three patients underwent salvage therapy; 51 (47.2%) received chemotherapy only, 22 (20.3%) received radiotherapy either alone or combined with chemotherapy, and 29 (26.9%) underwent salvage cytoreductive surgery. Multivariate regression analysis revealed that time to relapse after initial treatment, cancer antigen-125 level at recurrence, and the number of recurrent lesions were independent predictors of OSr. Incorporating these factors, we stratified patients into low-risk (n = 19), intermediate-risk (n = 43), and high-risk (n = 46) groups. The likelihood of cancer-specific death was higher in both the high-risk (HR = 8.948, 95% confidence interval [CI] = 3.498–22.893, P

OBJECTIVE This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) with or without carboplatin in Korean patients with recurrent ovarian cancer (ROC), fallopian tube, or primary peritoneal cancer. METHODS This retrospective study included 52 patients with ROC, fallopian tube, or primary peritoneal cancer who received PLD (50 mg/m2) between 1st December 2014 and 31th July 2016. RESULTS The mean number of chemotherapy cycles was 3.8 (range, 2 to 9) in the PLD monotherapy group and 7 (range, 2 to 13) in the PLD combined with carboplatin (PLD-C) group. In overall response rates and clinical beneficial rates, PLD monotherapy group shows 5.0% and 17.5%, and PLD-C group shows 33.3% and 75.0%. The mean progression-free survival (PFS) was 5 and 13 months in the PLD monotherapy and PLD-C groups, respectively. At 6 months after treatment initiation, absence of disease progression was confirmed in 6 (15%) and 10 (83.3%) patients in the PLD monotherapy and PLD-C groups. Hematological adverse events (e.g., neutropenia and thrombocytopenia) were more common in the PLD-C group (P

Objective To evaluate the safety and efficacy of prophylactic uterine artery embolization (UAE) before obstetrical procedures with high risk for massive bleeding. Materials and Methods A retrospective review of 29 female patients who underwent prophylactic UAE from June 2009 to February 2014 was performed. Indications for prophylactic UAE were as follows: dilatation and curettage (D&C) associated with ectopic pregnancy (cesarean scar pregnancy, n = 9; cervical pregnancy, n = 6), termination of pregnancy with abnormal placentation (placenta previa, n = 8), D&C for retained placenta with vascularity (n = 5), and D&C for suspected gestational trophoblastic disease (n = 1). Their medical records were reviewed to evaluate the safety and efficacy of UAE. Results All women received successful bilateral prophylactic UAE followed by D&C with preservation of the uterus. In all patients, UAE followed by obstetrical procedure prevented significant vaginal bleeding on gynecologic examination. There was no major complication related to UAE. Vaginal spotting continued for 3 months in three cases. Although oligomenorrhea continued for six months in one patient, normal menstruation resumed in all patients afterwards. During follow-up, four had subsequent successful natural pregnancies. Spontaneous abortion occurred in one of them during the first trimester. Conclusion Prophylactic UAE before an obstetrical procedure in patients with high risk of bleeding or symptomatic bleeding may be a safe and effective way to manage or prevent serious bleeding, especially for women who wish to preserve their fertility.

There are two opposing views regarding the prospects of establishing a regional environmental regime in Northeast Asia. The first view considers the environment as a dependent variable of progress towards regionalism and suggest that regional environmental cooperation is impeded by political rivalries, historical animosities and economic disparities among Northeast Asian countries. The opposing view treats the environment as an independent variable of sustainable regionalism. The premise of this view is that inter-state environmental cooperation can become a confidence building measure that will pave the way for improved regional relations. Regardless of which view proves in the end to be right, the high environmental interdependence of countries in Northeast Asia makes it imperative to create a framework to promote greater cooperation within the region. Given that the region lacks institutions for region-wide dialogue and cooperation, the formation of an effective regional environmental regime will be a long-term process. However, the process itself is pivotal as it can increase dialogue and exchanges from which a regional environmental regime can evolve, and hopefully, if given the political opportunity, will promote security and peace in the region.

In a world order characterized by ideological conflicts, low politics’ usually goes by the wayside. Policymakers focus on ‘high politics’ such as issues on state security, diplomacy and warfare. The September 11th attack was an epitome of terrorism that calls for not only the protection of territorial and political security of the state but also the safeguarding of the individual or group from all threats to human survival. This paper raises the issues on ‘environmental security’ and ‘human security,’ particularly in the context of East Asia and reviews the efforts of the United Nations to safeguard the global environment and human rights. Finally, this paper reflects on the future role of the United Nations in non‐traditional security arenas with special emphasis on its role in East Asia.

Background: Endometrial cancer is the most common malignancy of the female reproductive tract and the third most common cause of death from women's cancer. Risk factors of endometrial cancer include high levels of estrogen, obesity, diabetes mellitus, breast cancer, long term use of tamoxifen, late menopause, high blood pressure, and increasing age. Although the exact mechanisms in endometrial carcinogenesis due to chronic exposure are unclear, it is though that the pro-proliferative and DNA-damaging effects of estrogen and its metabolites, related with and insufficient counterbalance by progesterone, promote the hyper-proliferation and transformation of cells. Selective progesterone receptor modulator (SPRM) is an agent that acts on the progesterone receptor. Ulipristal acetate (UA) is one of SPRM and other SPRM, such as Mifepristone, showed inhibitory effect on various endometrial cancer cell lines. UA has been available as an emergency contraception and a treatment for uterine leiomyoma. The effect of UA on leiomyoma is decreasing neovascularization, proliferation, and viability. Objective: This study was undertaken to investigate antitumor effect of UA and to explore the effect of combination treatment with chemotherapy drug in endometrial cancer. Method: Inhibitory concentration (IC), proliferation assay, and migration assay were performed using Ishikawa, HEC-1-A, HEC-1-B, and/or patient-derived primary cancer cells (PCC). Different concentration of UA were treated in endometrial cancer cell lines and PCCs for the each assay. The CellTiter-Glo assay were performed to investigate IC50 in cell lines and PCCs. Crystal violet staining and wound healing assay were performed to examine cell proliferation and migration. Results: UA inhibited cell viability of endometrial cancer cell lines and PCCs at high concentration, most abviously 10uM in dose-dependent manner. In combination treatment assay with paclitaxel, UA showed synergistic anti-tumor effect with low-dose of paclitaxel on cell lines and PCCs. Conclusions: We showed that combination treatment of UA and paclitaxel effectively than single treatment by low dosage. In summary, we are actively exploring new effective applicable drugs for endometrial cancer, and our data suggest that UA may have therapeutic value with chemo-combination treatment of patients with endometrial cancer. Citation Format: Ha-Young Lee, A Ra Ko, Dong-Woo Kang, Yu-Seon Kim, Su-Min Kim, Tae-Wook Kang, Shin-Wha Lee, Yong-Man Kim. Anti-tumor effect of selective progesterone receptor modulator (ulipristal acetate) on endometrial cancer cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1191.