Search

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.

In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and update on sentinel lymph node mapping were reviewed for uterine corpus cancer. For ovarian cancer, 5 topics were selected including poly(ADP-ribose) polymerases inhibitors and immunotherapy. The other potential practice changers covered in this review were lymphadenectomy in advanced disease, secondary cytoreductive surgery in recurrent disease, weekly dose-dense regimen for first-line chemotherapy, incorporation of bevacizumab maintenance in platinum-sensitive recurrent disease, and effect of platinum-free interval prolongation. Conflicting opinions of academic societies on periodic pelvic examination were introduced in conjunction with relevant literature review. For the field of radiation oncology, results of 2 big trials, The Postoperative Radiation Therapy in Endometrial Carcinoma-3 and Gynecologic Oncology Group-258, for endometrial cancer and recent advance in high-dose-rate brachytherapy for cervical cancer were reported. Topics for breast cancer covered adjuvant capecitabine after preoperative chemotherapy, adjuvant pertuzumab and trastuzumab in early human epidermal growth factor receptor 2-positive disease, olaparib for metastatic cancer in patients with a germline BRCA mutation, 20-year risks of recurrence after stopping endocrine therapy at 5 years, and contemporary hormonal contraception and the risk of breast cancer.

Objective To evaluate survival impact of low anterior resection (LAR) in patients with epithelial ovarian cancer (EOC) grossly confined to the pelvis. Methods We retrospectively reviewed 397 patients who underwent primary staging surgery for treatment of 2014 International Federation of Gynecology and Obstetrics (FIGO) stage II–IIIA EOC: 116 (29.2%) IIA, 212 (53.4%) IIB, and 69 (17.4%) IIIA. Patients with grossly enlarged retroperitoneal lymph nodes positive for metastatic carcinoma were excluded. Of 92 patients (23.2%) with gross tumors at the rectosigmoid colon, 68 (73.9%) underwent tumorectomy and 24 (26.1%), LAR for rectosigmoid lesions. Survival outcomes between patients who underwent tumorectomy and LAR were compared using Kaplan-Meier curves. Results During the median follow-up of 55 months (range, 1–260), 141 (35.5%) recurrences and 81 (20.4%) deaths occurred. Age (52.8 vs. 54.5 years, p=0.552), optimal debulking (98.5% vs. 95.0%, p=0.405), histologic type (serous, 52.9% vs. 50.0%, p=0.804), FIGO stage (p=0.057), and platinum-based adjuvant chemotherapy ≥6 cycles (85.3% vs. 79.2%, p=0.485) were not different between groups. No significant difference in 5-year progression-free survival (PFS; 57.9% vs. 62.5%, p=0.767) and overall survival (OS; 84.7% vs. 63.8%, p=0.087), respectively, was noted between groups. Postoperative ileus was more frequent in patients subjected to LAR than those who were not (4/24 [16.7%] vs. 11/373 [2.9%], p=0.001). The 5-year PFS (60.3% vs. 57.9%, p=0.523) and OS (81.8% vs. 87.7%, p=0.912) between patients who underwent tumorectomy and those who did not were also similar. Conclusion Survival benefit of LAR did not appear to be significant in EOC patients with grossly pelvis-confined tumors.

Since after 2006 when the first edition of practice guidelines for gynecologic oncologic cancer treatment was released, the Korean Society of Gynecologic Oncology (KSGO) has published the following editions on a regular basis to suggest the best possible standard care considering updated scientific evidence as well as medical environment including insurance coverage. The Guidelines Revision Committee was summoned to revise the second edition of KSGO practice guidelines, which was published in July 2010, and develop the third edition. The current guidelines cover strategies for diagnosis and treatment of primary and recurrent ovarian cancer. In this edition, we introduced an advanced format based on evidence-based medicine, collecting up-to-date data mainly from MEDLINE, EMBASE, and Cochrane Library CENTRAL, and conducting a meta-analysis with systematic review. Eight key questions were raised by the committee members. For every key question, recommendations were developed by the consensus meetings and provided with evidence level and strength of the recommendation.

This study aimed to determine the factors influencing patients’ choice of physician at the first visit through database analysis of a tertiary hospital in South Korea. We collected data on the first treatments performed by physicians who had treated patients for at least 3 consecutive years over 10 years (from 2003 to 2012) from the database of Seoul National University’s affiliated tertiary hospital. Ultimately, we obtained data on 524,012 first treatments of 319,004 patients performed by 115 physicians. Variables including physicians’ age and medical school and patients’ age were evaluated as influencing factors for the number of first treatments performed by each physician in each year using a Poisson regression through generalized estimating equations with a log link. The number of first treatments decreased over the study period. Notably, the relative risk for first treatments was lower among older physicians than among younger physicians (relative risk 0.96; 95% confidence interval 0.95 to 0.98). Physicians graduating from Seoul National University (SNU) also had a higher risk for performing first treatments than did those not from SNU (relative risk 1.58; 95% confidence interval 1.18 to 2.10). Finally, relative risk was also higher among older patients than among younger patients (relative risk 1.03; 95% confidence interval 1.01 to 1.04). This study systematically demonstrated that physicians’ age, whether the physician graduated from the highest-quality university, and patients’ age all related to patients’ choice of physician at the first visit in a tertiary university hospital. These findings might be due to Korean cultural factors.

Objectives The objective of this study was to evaluate the risk factors for the failure of iliococcygeus suspension (ICG) for uterine prolapse and estimate its long-term success rates using a clinically relevant criterion. Study design This retrospective cohort study included 144 women who underwent transvaginal reconstructive surgery including ICG for symptomatic pelvic organ prolapse. Surgical failure was defined as anatomic recurrence (descent of the vaginal apex beyond the halfway point of the vagina or descent of the anterior or posterior vaginal wall beyond the hymen), symptomatic recurrence (vaginal bulge symptoms), or retreatment for prolapse. Results During the median 4-year follow-up period, surgical failure was observed in 20 women (13.9%). Multivariate analysis with the Cox proportional hazard model showed that advanced prolapse (preoperative pelvic organ prolapse quantification [POP-Q] stage >II and point C >0) and uterus-saving techniques were independent risk factors for failure. When the ICG was performed as a vault suspension procedure together with hysterectomy, the estimated 4-year success rates were 100% for mild prolapse (POP-Q stage II or point C ≤0) and 91.2% for advanced prolapse. When the procedure was done as a hysteropexy, the corresponding success rates decreased to 75.3% and 48.0%, respectively. Conclusions This study indicates that the severity of prolapse and the uterus-saving technique affect the prognosis after ICG. The ICG provides a durable apical vaginal support when performed together with hysterectomy, irrespective of the severity of the prolapse. In addition, it appears to be an acceptable hysteropexy option for mild uterine prolapse.

The purpose of this study was to investigate the antiproliferative effect of active hexose correlated compound (AHCC), derived from basidiomycete mushroom culture, on ovarian cancer cell lines. An in vitro growth inhibition assay was performed using AHCC in ovarian cancer cell lines. Western blotting was performed to investigate the mechanism of the observed antiproliferative effect of AHCC. We identified that ovarian cancer cell viability was significantly reduced through treatment with AHCC compared to that in the control. AHCC inhibited constitutive signal transducer and activator of transcription 3 (STAT3) phosphorylation in ovarian cancer cell lines. In contrast, treatment with pervanadate, a protein tyrosine phosphatase inhibitor, reversed AHCC-induced STAT3 suppression. AHCC treatment induced the expression of SHP-1, a protein tyrosine phosphatase, and suppressed the expression of cyclin D1, Bcl-2, Mcl-1, survivin, and VEGF, which are STAT3-regulated gene products that are associated with cell proliferation or apoptosis. These results suggest that AHCC has an antiproliferative effect on ovarian cancer cell lines, via STAT3 phosphorylation; thus, this compound has the potential to be a complementary and alternative anticancer therapy for the treatment of ovarian cancer.

Objective A prospective, randomized controlled trial was conducted to evaluate the efficacy of nerve-sparing radical hysterectomy (NSRH) in preserving bladder function and its oncologic safety in the treatment of cervical cancer. Methods From March 2003 to November 2005, 92 patients with cervical cancer stage IA2 to IIA were randomly assigned for surgical treatment with conventional radical hysterectomy (CRH) or NSRH, and 86 patients finally included in the analysis. Adequacy of nerve sparing, radicality, bladder function, and oncologic safety were assessed by quantifying the nerve fibers in the paracervix, measuring the extent of paracervix and harvested lymph nodes (LNs), urodynamic study (UDS) with International Prostate Symptom Score (IPSS), and 10-year disease-free survival (DFS), respectively. Results There were no differences in clinicopathologic characteristics between two groups. The median number of nerve fiber was 12 (range, 6 to 21) and 30 (range, 17 to 45) in the NSRH and CRH, respectively (p

Metformin, an oral biguanide for the treatment of type II diabetes, has been shown to have anticancer effects in ovarian cancer. Energy starvation induced by metformin causes endoplasmic reticulum stress-mediated unfolded protein response (UPR) and autophagy. UPR and autophagy act as a survival or death mechanism in cells. In this study, we observed that metformin-induced apoptosis was relieved by autophagy and the PERK/eIF2α pathway in ovarian cancer cells, but not in peripheral blood mononuclear cells (PBMC) or 'normal' ovarian surface epithelial cells (OSE). Increased PARP cleavage and increased LC3B-II with ATG5-ATG12 complex suggested the induction of apoptosis and autophagy, respectively, in metformin-treated ovarian cancer cells. Accumulation of acidic vacuoles in the cytoplasm and downregulation of p62 further supported late-stage autophagy. Interestingly, metformin induced interdependent activation between autophagy and the UPR, especially the PERK/eIF2α pathway. Inhibition of autophagy-induced PERK inhibition, and vice versa, were demonstrated using small molecular inhibitors (PERK inhibitor I, GSK2606414; autophagy inhibitor, 3-MA, and BafA1). Moreover, autophagy and PERK activation protected ovarian cancer cells against metformin-induced apoptosis. Metformin treatment in the presence of inhibitors of PERK and autophagy, however, had no cytotoxic effects on OSE or PBMC. In conclusion, these results suggest that inhibition of autophagy and PERK can enhance the selective anticancer effects of metformin on ovarian cancer cells. © 2015 Wiley Periodicals, Inc.

Success factors of laparoscopic nerve-sparing radical hysterectomy (LNRH) to preserve bladder function are little known despite its widespread use. Thus, we conducted a protocol-based prospective cohort study to evaluate clinicopathologic factors for preserving autonomic nerves and its impact on duration of postoperative catheterization (DPC). From 2012 to 2014, 30 patients with stage IB1 to IIA2 cervical cancer were recruited prospectively to undergo LNRH. All procedures were performed on the left side of the patients by one gynecologic oncologist. Extent of resection and preservation of autonomic nerves were documented in the protocol during LNRH. All patients received laparoscopic type C1 radical hysterectomy, where extent of resection and preservation of autonomic nerves were not different between the right and left sides. Stage IB1 disease was associated with the reduced risk of injury of the left junctions between the hypogastric and the splanchnic nerves; between the splanchnic nerve and the vesical branch of the pelvic plexus (S–V junction) (adjusted odds ratios, 0.06 and 0.06; 95 % confidence intervals, 0.01–0.92 and 0.01–0.48); the right S–V junction with marginal significance (adjusted odds ratio, 0.18; 95 % confidence interval, 0.03–1.06). Furthermore, bilateral preservation of autonomic nerves decreased DPC significantly when compared with failure or unilateral preservation (median, 6 days vs. 34 days or 57 days; P

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.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.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).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.

Background/aim To investigate the abundance of programmed death-ligand 1 (PD-L1) expression and identify rational candidates for anti-PD-1/PD-L1 immunotherapies in cervical cancer. Patients and methods In 27 patients with FIGO stage IB1-IIA cervical cancer, paraffin-embedded tumors were immunohistochemically stained with PD-L1 antibody. The correlation of tumoral PD-L1 expression with clinicopathological factors and survival outcomes were evaluated. Results Overall, PD-L1 expression was primarily detected in 12 (44.4%) patients. All tumors with PD-L1 expression were squamous cell carcinomas (SqCC). In subgroup analysis of SqCC, higher PD-L1 expression was associated with low preoperative serum SqCC antigen level (p=0.030) and no parametrial invasion (p=0.048). The 5-year progression-free survival (83.3% vs. 50.0%. p=0.136) and overall survival rates (90.9% vs. 83.3%, p=0.615) were superior in patients with PD-L1 expression that in those without PD-L1 expression; however, neither was significant. Conclusion Patients with SqCC and favorable clinicopathological factors could be candidates for anti-PD-1/PD-L1 immunotherapy in cervical cancer.

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.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 cmThe 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 cmThe tumor volume index and cord blood biomarkers for heart failure can be promising prognostic markers for neonatal survival in sacrococcygeal teratoma.

We evaluated the effect of red ginseng on toxicity, health-related quality of life (HRQL) and survival after adjuvant chemotherapy in patients with epithelial ovarian cancer (EOC). A total of 30 patients with EOC were randomly assigned to placebo (n = 15) and red ginseng groups (n = 15). All patients took placebo or red ginseng (3000 mg/day) for three months. Then, we compared changes of genotoxicity, HRQL and survival between the two groups. As a result, red ginseng reduced micronuclei yield in comparison with placebo despite no difference of binucleated cells index. Although red ginseng increased serum levels of alanine aminotransferase and aspartate aminotransferase significantly, they were within the normal value. Moreover, there were no differences in adverse events between placebo and red ginseng groups. In terms of HRQL, red ginseng was associated with improved emotional functioning and decreased symptoms of fatigue, nausea and vomiting, and dyspnea, reduced anxiety and interference affecting life and improved daytime somnolence. However, there was no effect of red ginseng on prognosis of EOC. Conclusively, red ginseng may be safe and effective to reduce genotoxicity and improve HRQL despite no benefit of survival in patients with EOC who received chemotherapy.

Background Anticancer effect of ginsenoside Rh2 has been found in various cancer cells. However, the anticancer effect of Rh2 in endometrial cancer cells is still unclear. We aimed to determine the anticancer effect of Rh2 and elucidate its mechanism in endometrial cancer cells, using HEC1A and Ishikawa cell lines, in this study. Methods Cell proliferation was assessed by MTT assay, and cell apoptosis was visualized by TdT mediated-dUTP Nick-End Labeling (TUNEL) method. Western blot were performed to detect the expression of apoptosis and epithelial-mesenchymal transition (EMT)-related proteins. Further, cell invasion and migration assays were conducted to estimate cell migration and invasion abilities. Results Rh2 treatment significantly suppressed cell proliferation in HEC1A and Ishikawa cells, in dose-dependent manner. Levels of cleaved poly adenosine diphosphate-ribose polymerase (PARP) and cleaved caspase-3 increased in the both cell lines with Rh2 compared with control. In Western blotting analysis after Rh2 treatment, the expression of E-cadherin increased, while the expression of EMT-related proteins including vimentin, TGF-β, and Snail markedly decreased in both cell lines. The cell invasion and migration assays results indicated that Rh2 inhibited the cell invasion and migration in HEC1A cells. Conclusions Our findings suggested that Rh2 exerts the anticancer effect in endometrial cancer cells through the apoptosis induction and EMT inhibition.

Objective This study aims to evaluate practice patterns for managing hereditary ovarian cancer among Korean gynecologic oncologic physicians. Methods Members of the Korean Society of Gynecologic Oncology participated in the inaugural Hereditary Gynecologic Cancer Symposium or were invited to this survey by e-mail from January to February 2016. The survey was conducted using a self-administered questionnaire. Results Most physicians (66.7%, 36/54) responded to draw a pedigree of patients with a family history. The rate of genetic test recommendations for patients at risk for ovarian cancer was high (96.3%, 52/54). Physicians tended to select appropriate candidates for the genetic test. Of the respondents, genetic counseling was commonly performed before the genetic test (76.6%, 36/47) and provided by the specialist consultant(s) (78.7%, 37/47) or the physician alone (12.8%, 6/47). Participants showed mature response to risk management for the BRCA carriers: at least annual gynecologic surveillance (89.4%, 42/47), recommendation for chemoprevention (76.6%, 36/47), and advice for risk-reducing salpingo-oophorectomy (85.1%, 40/47). Risk-reducing salpingectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy was considered to recommend in most of respondents (91.5%, 43/47). Conclusions Gynecologic oncologic physicians in Korea had high awareness to genetic risk assessment, candidate selection to genetic test, and risk-reducing strategies for the management of hereditary ovarian cancer.

In 2016, 13 topics were selected as major research advances in gynecologic oncology. For ovarian cancer, study results supporting previous ones regarding surgical preventive strategies were reported. There were several targeted agents that showed comparable responses in phase III trials, including niraparib, cediranib, and nintedanib. On the contrary to our expectations, dose-dense weekly chemotherapy regimen failed to prove superior survival outcomes compared with conventional triweekly regimen. Single-agent non-platinum treatment to prolong platinum-free-interval in patients with recurrent, partially platinum-sensitive ovarian cancer did not improve and even worsened overall survival (OS). For cervical cancer, we reviewed robust evidences of larger-scaled population-based study and cost-effectiveness of nonavalent vaccine for expanding human papillomavirus (HPV) vaccine coverage. Standard of care treatment of locally advanced cervical cancer (LACC) was briefly reviewed. For uterine corpus cancer, new findings about appropriate surgical wait time from diagnosis to surgery were reported. Advantages of minimally invasive surgery over conventional laparotomy were reconfirmed. There were 5 new gene regions that increase the risk of developing endometrial cancer. Regarding radiation therapy, Post-Operative Radiation Therapy in Endometrial Cancer (PORTEC)-3 quality of life (QOL) data were released and higher local control rate of image-guided adaptive brachytherapy was reported in LACC. In addition, 4 general oncology topics followed: chemotherapy at the end-of-life, immunotherapy with reengineering T-cells, actualization of precision medicine, and artificial intelligence (AI) to make personalized cancer therapy real. For breast cancer, adaptively randomized trials, extending aromatase inhibitor therapy, and ribociclib and palbociclib were introduced.

ObjectivesThe aims of study were to determine the predictive value of preoperative magnetic resonance imaging (MRI) for parametrial invasion (PMI) and to develop a predictive model for PMI in patients with stage IB1 to IIA2 cervical cancer.MethodsWe retrospectively analyzed patients with stage IB1 to IIA2 cervical cancer (n = 215) who underwent radical hysterectomy between 2003 and 2014. The presence of PMI from postoperative pathological reports and its association with preoperative MRI findings were evaluated. We developed a predictive model for PMI using independent predictive factors identified by logistic regression and estimated its predictive performance.ResultsThirty patients (14.0%) had PMI from postoperative pathological reports. Among the preoperative MRI findings, a greater tumor diameter (4.2 vs 2.0 cm;P <0.001), a larger tumor volume (92.6 vs 12.7 cm3;P< 0.001), the presence of PMI (53.3% vs 8.6%;P< 0.001), and upper vaginal involvement (73.3% vs 22.7%;P< 0.001) were significantly associated with PMI. Multivariate analysis identified tumor volume (odds ratio, 7.0; 95% confidence interval, 2.63–18.53;P< 0.001) and PMI (odds ratio, 6.1; 95% confidence interval, 2.31–15.97;P< 0.001) from preoperative MRI findings as independent predictive factors for PMI. Our predictive model demonstrates that the presence of PMI or a tumor volume of greater than 18.0 cm3has a higher sensitivity (86.7% vs 53.3%) and lower specificity (74.6% vs 91.4%) than the presence of PMI alone. Specifically, the model's negative predictive value was superior to that of PMI only (97.2% vs 92.3%). In the low-risk group, defined as preoperative MRI findings suggesting no PMI and a tumor volume of 18.0 cm3or less, the proportion of false negative cases was just 2.8%.ConclusionsWhen tumor volume with findings suggesting that PMI is considered, preoperative MRI is useful in excluding PMI. A predictive model based on preoperative MRI findings seems to be valuable in identifying potential candidates for less radical surgery in stage IB1 to IIA2 cervical cancer.

Objective The aim of this study is to evaluate the associations of pre- and intra-operative variables including comprehensive geriatric assessment (CGA) with surgical complications in elderly patients who underwent primary surgery for gynecologic cancer. Methods Sixty consecutive patients ≥70years of age who were scheduled to undergo elective surgery for the treatment of gynecologic cancer were preoperatively assessed by CGA. Every category of CGA, performance status (PS), and brief fatigue inventory (BFI) as well as surgical complexity were evaluated for 30-day surgical complications. Results The overall postoperative complication rate was 30.0% (18/60) including 9 (15.0%) major and 8 (13.3%) multiple complications. Univariate analysis revealed that dependent instrumental activity of daily living (IADL) was associated with any ( p =0.023) and multiple complications ( p =0.019). Poor PS was associated with major ( p =0.021) and multiple complications ( p =0.014). Multivariate logistic regression analysis revealed that high surgical complexity was the most independent predictor of any, major, and multiple complications, whereas poor PS was the independent predictor only for multiple complications (odds ratio 10.7, 95% confidence interval 1.7 to 90.2, p =0.043). There was no CGA component which could independently predict postoperative complications. Conclusion Surgical complexity can predict any, major, and multiple postoperative complications, while PS seems to be useful in predicting multiple complications in elderly patients with gynecologic cancer. In this small study, a CGA was not useful in predicting postoperative complications.

ObjectiveThe purpose of this study was to determine the prognostic factors in women with synchronous endometrial and ovarian cancers.MethodsMedical records of 3240 patients with endometrial cancer who had undergone primary surgery were collected from 7 institutions and were retrospectively reviewed. The progression-free survival (PFS) and overall survival (OS) curves and rates were calculated using the Kaplan-Meier method. Multivariate analysis to determine independent prognostic factors was performed using the Cox regression model.ResultsThe incidence of synchronous endometrial/ovarian cancer was 3.8% (123/3240 women). During the median follow-up period of 66 months, 33.3% and 26.1% of women developed recurrences and reported cancer-related deaths. The 5-year PFS and 5-year OS for all 123 women were 66.9% and 80.0%, respectively. In multivariate analysis, pretreatment CA-125 and tumor stage of the ovary showed prognostic significance about PFS (P = 0.043 and P = 0.027) and OS (P = 0.047 and P = 0.031), respectively.ConclusionsPretreatment CA-125 and tumor stage of the ovary were independent prognostic factors for recurrence and survival.

Ovarian cancer is the most lethal gynecologic malignancy among women worldwide and is presumed to result from the presence of ovarian cancer stem cells. To overcome the limitation of current anticancer agents, another anticancer strategy is necessary to effectively target cancer stem cells in ovarian cancer. In many types of malignancies, including ovarian cancer, metformin, one of the most popular antidiabetic drugs, has been demonstrated to exhibit chemopreventive and anticancer efficacy with respect to incidence and overall survival rates. Thus, the metabolic reprogramming of cancer and cancer stem cells driven by genetic alterations during carcinogenesis and cancer progression could be therapeutically targeted. In this review, the potential efficacy and anticancer mechanisms of metformin against ovarian cancer stem cells will be discussed.

In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7-9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review.

Circulating tumor cells (CTCs) have received enormous attention as a novel biomarker in various malignant diseases. We investigated the clinical association between the presence of perioperative CTCs and survival outcomes in women with ovarian cancer. In a total of 30 women who were scheduled to undergo a surgical treatment for ovarian cancer, peripheral blood samples were obtained before and after surgery. CTCs were isolated and counted using the optimized tapered-slit filter (TSF) platform. The association between the presence of perioperative CTCs and tumor features was evaluated. The impact of the presence of perioperative CTCs on progression-free survival (PFS) and overall survival (OS) rates were analyzed using a Kaplan–Meier method. The median age was 58 (range, 24–77) years, and the median follow-up period was 31.5 (range, 1–41) months. Overall, the CTC detection rate was not significantly different before and after surgery (76.7% vs 57.1%, P = .673). The presence of postoperative CTCs was not significantly associated with 3-year PFS (29.1% vs 58.3%, P = .130) and OS (84.4% vs 80.0%, P = .559) rates in the whole study population. In advanced stage, PFS rate in patients with postoperative CTCs had lower PFS rates than those without postoperative CTCs, although there was no statistical significance (18.8% vs 57.1%, P = .077). Postoperative CTC was more frequently detected in women who had lymph node involvement than those who did not (7/7 [100%] vs 3/10 [30.0%], P = .010). The presence of postoperative CTCs as detected using the TSF platform seems to be associated with poorer PFS rates in women with ovarian cancer of advanced stage. Further study with a larger population is warranted to validate our study findings.

Ovarian cancer presents at an advanced stage in more than 75% of patients. Early detection has great promise to improve clinical outcomes. Although the advancing proteomic technologies led to the discovery of numerous ovarian cancer biomarkers, no screening method has been recommended for early detection of ovarian cancer. Complexity and heterogeneity of ovarian carcinogenesis is a major obstacle to discover biomarkers. As cancer arises due to accumulation of genetic change, understanding the close connection between genetic changes and ovarian carcinogenesis would provide the opportunity to find novel gene-level ovarian cancer biomarkers. In this review, we summarize the various gene-based biomarkers by genomic technologies, including inherited gene mutations, epigenetic changes, and differential gene expression. In addition, we suggest the strategy to discover novel gene-based biomarkers with recently introduced next generation sequencing.

During the tumorigenesis, cancer cells are frequently exposed to metabolic stress which is derived from altered cancer cell metabolism as well as unfavorable tumor microenvironment, such as hypoxia and glucose deprivation. Cancer cells need to respond to these stress stimuli properly through inducing cellular stress responses, such as unfolded protein response and autophagy, for cell survival. Therefore, modulation of these stress responses has been investigated as an alternative anticancer strategy, although their therapeutic clinical roles remain to be determined. In this review, we will discuss the cellular stress responses in cancer cells, the alternative anticancer strategy targeting unfolded protein response and/or autophagy, and the role of phytochemicals, which include resveratrol, genistein, curcumin, epigallocatechin-3-gallate and quercetin, in modulating the cellular stress responses.

The endoplasmic reticulum (ER) is responsible for protein processing. In rapidly proliferating tumor cells, the ER tends to be overloaded with unfolded and misfolded proteins due to high metabolic demand. With the limited protein-folding capacity of the ER, tumor cells often suffer from more ER stress than do normal cells. Thus, cellular stress responses to cope with ER stress, such as the unfolded protein response (UPR) and autophagy, might be more activated in cancer cells than in normal cells. The complex signaling pathways from the UPR to autophagy provide promising druggable targets; a number of UPR/autophagy-targeted anticancer agents are currently in development in preclinical and clinical studies. In this short review we will discuss the potential anticancer efficacy of modulators of cellular stress responses, especially UPR and autophagy, on the basis of their signaling pathways. In addition, the current developmental status of the UPR/autophagy-targeted agents will be discussed.

Objective To evaluate the efficacy of loop electrosurgical excision procedure (LEEP) combined with cold coagulation for treating cervical intraepithelial neoplasia (CIN). Methods We reviewed clinic-pathologic data of 498 patients treated with LEEP alone (n=354), and LEEP combined with cold coagulation (n=144) between January 2000 and December 2011. After LEEP, we followed up all patients by using Papanicolaou smear and human papillomavirus (HPV) test, and evaluated abnormal cervical cytology-free interval and high-risk HPV infection-free interval. Moreover, we investigated independent factors affecting abnormal cervical cytology or high-risk HPV infection after LEEP. Results Abnormal cervical cytology-free interval was longer in patients treated with LEEP combined with cold coagulation than in those treated with LEEP alone (mean, 92.4 vs. 84.4 months; P=0.01), and patients treated with LEEP combined with cold coagulation also showed longer high-risk HPV infection-free interval than those treated with LEEP alone (mean, 87.6 vs. 59.1 months; P=0.01). Moreover, CIN 3 and cold coagulation were factors affecting abnormal cervical cytology after LEEP (adjusted hazard ratios, 1.90 and 0.61; 95% confidence intervals, 1.27 to 2.84 and 0.39 to 0.96), and CIN 3, positive deep cervical margin and cold coagulation were also factors affecting high-risk HPV infection after LEEP (adjusted hazard ratios, 2.07, 4.11, and 0.64; 95% confidence intervals, 1.38 to 3.08, 1.63 to 10.39, and 0.43 to 0.96). When we performed subgroup analyses for patients with CIN 2 or CIN 3, the result were similar. Conclusion LEEP combined with cold coagulation may be more effective for treating CIN than LEEP alone. Moreover, cold coagulation may decrease the risk of potential of recurrence after LEEP.

OBJECTIVE The prognostic significance of positive peritoneal cytology in patients with early-stage endometrial cancer (Stage 1 or 2) is controversial and perhaps depends on the presence of other factors. The relationship of other prognostic factors with positive peritoneal cytology remains unclear. This study aimed to investigate the association between positive peritoneal cytology and prognostic factors and the influence of positive peritoneal cytology on survival in patients with early-stage endometrial cancer. METHODS We identified 351 articles on the PubMed, Cochrane and Embase databases using a combination of the following search terms: endometrial cancer, endometrial carcinoma, positive peritoneal cytology and positive peritoneal washing. When filtered for studies comparing positive peritoneal cytology with negative peritoneal cytology in early-stage endometrial cancer, 11 retrospective studies met the selection criteria. Meta-analyses were performed using Review Manager 5.3 software. RESULTS In patients with surgical stage 1 or 2 early-stage endometrial cancer, the incidence of Grade 3 was higher and 5-year overall survival was worse in patients with positive peritoneal cytology compared with negative peritoneal cytology. However, the incidence of Grade 1 was lower in those with positive peritoneal cytology compared with negative peritoneal cytology. In patients with surgical stage 1 early-stage endometrial cancer, the incidence of myometrial invasion ≥1/2 tended to be higher and 5-year progression-free survival was worse in the positive peritoneal cytology group than the negative peritoneal cytology group. However, the incidence of myometrial invasion

Background The focus on translational research in clinical trials has the potential to generate clinically relevant genetic data that could have importance to patients. This raises challenging questions about communicating relevant genetic research results to individual patients. Methods An exploratory pharmacogenetic analysis was conducted in the international ovarian cancer phase III trial, AGO-OVAR 16, which found that patients with clinically important germ-line BRCA1/2 mutations had improved progression-free survival prognosis. Mechanisms to communicate BRCA results were evaluated, because these findings may be beneficial to patients and their families. Results Communicating individual BRCA results was not anticipated during clinical trial design. Consequently, options were not available for patients to indicate their preference for receiving their individual results when they signed pharmacogenetic informed consent. Differences in local requirements, clinical practice, and opinion regarding the ethical aspects of how to convey genetic results to patients are all potential barriers to returning individual BRCA results to patients. Communicating the aggregate BRCA result from this study provided clinical investigators with a mechanism to disseminate the overall study finding to patients while taking individual circumstances, local guidelines and clinical practice into account. Conclusion This study illustrates the importance of increasing the clarity and scope of informed consent and the need for patient engagement to ensure clinical trial participants can indicate their preference regarding receipt of potentially important individual pharmacogenetic results. Trial registration This study was registered in the NCT Clinical Trial Registry under NCT00866697 on March 19, 2009, following approval from participating ethics committees (Additional file 1). Electronic supplementary material The online version of this article (doi:10.1186/s12910-016-0144-y) contains supplementary material, which is available to authorized users.

OBJECTIVE The efficacy of systematic lymphadenectomy is controversial for improving overall survival in patients with endometrial cancer. Thus, we performed a meta-analysis comparing the efficacy for overall survival between systematic and unsystematic lymphadenectomies. METHODS After an extensive literature search between January 2000 and August 2010, we analyzed nine studies (two randomized controlled trials and seven observational studies) involving 16 995 patients with endometrial cancer. Systematic versus unsystematic lymphadenectomy was defined using two criteria: removal of ≥10-11 versus ≤10-11 lymph nodes; systematic dissection of lymphatic tissues versus no lymphadenectomy other than suspicious lymph nodes. RESULTS In all studies, systematic lymphadenectomy improved overall survival, compared with unsystematic lymphadenectomy (hazard ratio, 0.89; 95% confidence interval, 0.82-0.97), whereas its efficacy was not shown in two randomized controlled trials (hazard ratio, 1.05; 95% confidence interval, 0.84-1.31). Removal of ≥10-11 lymph nodes improved overall survival, compared with that of ≤10-11 lymph nodes (hazard ratio, 0.88; 95% confidence interval, 0.81-0.97) in spite of no difference in overall survival between systematic dissection of lymphatic tissues and no lymphadenectomy other than suspicious lymph nodes (hazard ratio, 0.94; 95% confidence interval, 0.77-1.15). Furthermore, systematic lymphadenectomy increased overall survival in patients with intermediate- or high-risk endometrial cancer (hazard ratio, 0.77; 95% confidence interval, 0.70-0.86) in spite of no efficacy in those with low-risk endometrial cancer (hazard ratio, 1.14; 95% confidence interval, 0.87-1.49). CONCLUSIONS These findings suggest that the efficacy of systematic lymphadenectomy, defined as removal of more than about 10 lymph nodes, is limited for improving overall survival in patients with low-risk endometrial cancer, whereas it is efficient to increase overall survival in patients with intermediate- or high-risk endometrial cancer.

Reflecting the worldwide aging trend and close association of aging with cancer, geriatric oncology is now growing beyond its pioneer years. Nevertheless, geriatric oncology in the gynecologic field is in the beginning stage; indeed, there is no geriatric specialist who is trained in this particular field of gynecologic oncology. Therefore, we held the first workshop in geriatric gynecologic oncology. In this review, we summarize what we discussed at the workshop and provide evidence-based recommendations for the diagnosis and treatment of gynecologic cancer in elderly individuals.

Aim: There is controversy regarding the effect of obesity on the treatment and survival of ovarian cancer. This study examined the impact of obesity on the treatment and survival outcomes of epithelial ovarian cancer. Methods: The medical records of patients undergoing surgery for epithelial ovarian cancer (EOC) between January 2000 and February 2010 were reviewed. Patient demographics, surgical outcomes, clinicopathological factors and survival were evaluated and compared according to the body mass index (BMI). The Asian BMI criteria for Koreans were used. Results: Of a total of 486 patients identified, 31 (6.4%) were underweight (BMI 0.05) or overall survival (P > 0.05) according to the BMI. No difference in progression free survival (P > 0.05) or overall survival (P > 0.05) could be found, even in the subcohort of stages III and IV. Conclusion: Obesity itself does not affect the surgical and clinicopathological outcomes or even survival in EOC patients.

The total synthesis of optically active phenylbutenoid dimers 1, 3, and ent-3 is described. The key step to access optically active cyclohexene rings was achieved by Diels-Alder reaction of chiral acryloyloxazolinone 9 and phenylbetadiene 10.

The poor prognosis in the treatment of ovarian cancer is mainly attributed to chemoresistance. The development of new strategies is urgently necessary to overcome chemoresistance because of the low efficacy of the current standard chemotherapy in ovarian cancer. Metabolic alterations have been suggested to have a crucial role in cancer development. The key metabolic changes in cancer include aerobic glycolysis and macromolecular synthesis, causing antiapoptosis in cancer cells. Therefore, the manipulation of the metabolic derangement could be an effective strategy to overcome chemoresistance in ovarian cancer. In this review, we will discuss metabolic interventions as promising anticancer strategies in ovarian cancer, focusing on the glycolytic, mitochondrial apoptotic, and necrotic pathways. In addition, the role of p53 in relation to metabolic alterations in cancer will be mentioned.

E-mail: heejong@krict.re.krReceived December 28, 2010, Accepted February 14, 2011Inhibition of BACE 1 activity is considered as a promising therapeutic target for Alzheimer’s Disease (AD).Synthesis and inhibitory activities of (4-arylpiperazinyl)piperidines by bioisosteric replacement of a biarylgroup with an arylpiperazine as BACE 1 inhibitors are described. The resulting (4-arylpiperazinyl)piperidinesrepresent novel nonpeptide BACE 1 inhibitors with improved in vitro potency.Key Words : Alzheimer’s Disease (AD), BACE 1 (β-secretase), Non-peptidomimetic inhibitors, Arylpiper-azinylpiperidinesIntroductionAlzheimer’s disease (AD) is the most common form ofdementia with clinical symptoms of memory loss andimpairment on daily living activity.

Colposcopy-directed punch biopsy (punch biopsy) and endocervical curettage (ECC) are accompanied by considerable pain. However, many physicians perform these procedures without adequate pain management. Therefore, identification of factors affecting pain experienced during the procedures may encourage physician effort in selective pain management. This study investigated factors affecting the severity of pain experienced during punch biopsy and ECC in an outpatient clinic of gynecologic oncology department. In this retrospective, exploratory study, a total of 101 Korean patients with abnormal cervical cytology underwent punch biopsy and ECC under a paracervical block performed for pain relief. Residents under training performed these procedures and recorded patient-reporting maximum Numeric Rating Scale (NRS) scores experienced during the procedures. Residents were classified into four outpatient clinic training groups (1st–4th); the group designators correspond to the resident's experience in performing these procedures. A linear mixed model adjusted for physician factors such as either residents or outpatient clinic training groups was used to analyze the association between each variable and maximum NRS score. Among the outpatient clinic training groups, maximum NRS scores significantly decreased in the 4th group, compared with those in the 1st group although those were not different among groups when adjusted for residents. Some of cervical cytology findings and discrepancies between the severity of cervical cytology results and those of punch biopsy or ECC showed significant associations with maximum NRS scores. However, when adjusted for either residents or outpatient clinic training groups, maximum NRS scores were not different by age, body mass index, presence of menopause, cervical cytology findings, discrepancies between the severity of cervical cytology results and those of punch biopsy or ECC, and tissue volume. There are no significant factors affecting the severity of pain experienced during punch biopsy and ECC.

The expression patterns of the key DNA damage response-related proteins, ataxia-telangiectasia and tfiih/ner complex atp-dependent 5'-3' dna helicase subunit rad3 (RAD3)-related (ATR) and ataxia-telangiectasia-mutated (ATM) proteins in ovarian cancer are not well-known. This study aimed to evaluate the expressions of ATR and ATM proteins, and to investigate their clinical significance in epithelial ovarian carcinoma (EOC).The expressions of nuclear/cytoplasmic Ser428-phosphorylated ATR (p-ATR) and Ser1981-phosphorylated ATM (p-ATM) were evaluated by immunohistochemistry in 100 patients with EOC. The clinical significances of p-ATR and p-ATM protein expression were evaluated in terms of tumor progression and survival.Low expression of cytoplasmic p-ATR was significantly associated with advanced stage, serous histology, large residual mass, and high preoperative serum CA125 level. Univariate survival analysis revealed that low expression of cytoplasmic p-ATR protein was significantly associated with poor disease-free survival and poor overall survival.Our study demonstrates that cytoplasmic ATR protein might serve as a prognostic biomarker for patients with EOC.