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Background and Objective: The therapeutic role of systematic lymph node dissection (LND) remains unclear in advanced epithelial ovarian cancer (EOC), especially during interval debulking surgery (IDS) performed after neoadjuvant chemotherapy (NAC). We analyzed the therapeutic and prognostic roles of systematic LND in advanced EOC patients., Methods: Data from consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV disease, who underwent optimal IDS (<1cm) after NAC, were obtained via a retrospective chart review. Patients were classified into a lymph node sampling (LNS; node count <20) group and an LND (node count ≥20) group., Results: Among 133 study patients, 65 and 68 underwent LND and LNS, respectively, during IDS. Overall survival (OS) was significantly better in the LND group than in the LNS group. In subgroup analysis with negative lymphadenopathy on preoperative imaging, progression-free survival (PFS) and OS were significantly better in the LND group than in the LNS group. Follow-up of subsequent recurrences showed significantly lower nodal and peritoneal recurrence rates among patients who underwent LND. Multivariate analysis identified LND as an independent prognostic factor for PFS and OS., Conclusion: Systematic LND may have therapeutic value in advanced EOC patients treated with NAC and IDS., (© 2017 Wiley Periodicals, Inc.)

The prognostic significance of pelvic and para-aortic lymphadenectomy during primary debulking surgery for advanced-stage ovarian cancer remains unclear. This study aimed to evaluate the survival impact of lymph node dissection (LND) in patients treated with optimal cytoreduction for advanced ovarian cancer. Data from 158 consecutive patients with stage IIIC-IV disease who underwent optimal cytoreduction (<1 cm) were obtained via retrospective chart review. Patients were classified into two groups: (1) lymph node sampling (LNS), node count <20; and (2) LND, node count ≥20. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Among the included patients, 96 and 62 patients underwent LND and LNS as primary debulking surgery, respectively. There were no differences in the extent of debulking surgical procedures, including extensive upper abdominal surgery, between the groups. Patients who underwent LND had a marginally significantly improved PFS (P = 0.059) and significantly improved OS (P < 0.001) compared with those who underwent LNS. In a subgroup with negative lymphadenopathy on preoperative computed tomography scans, revealed LND correlated with a better PFS and OS (P = 0.042, 0.001, respectively). Follow-ups of subsequent recurrences observed a significantly lower nodal recurrence rate among patients who underwent LND. A multivariate analysis identified LND as an independent prognostic factor for PFS (hazard ratio [HR], 0.629; 95% confidence interval [CI], 0.400-0.989) and OS (HR, 0.250; 95% CI, 0.137-0.456). In conclusion, systematic LND might have therapeutic value and improve prognosis for patients with optimally cytoreduced advanced ovarian cancer.

Clinical practice guidelines for gynecologic cancers have been developed by academic society from several countries. Each guideline reflected their own insurance system and unique medical environment, based on the published evidence. 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 develop the third edition of the guidelines in an advanced format based on evidence-based medicine, embracing up-to-date clinical trials and qualified Korean data. These guidelines cover strategies for diagnosis and treatment of primary and recurrent cervical cancer. The committee members and many gynecologic oncologists derived key questions through discussions, and a number of relevant scientific literature were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, along with the details. The objective of these practice guidelines is to establish standard policies on issues in clinical practice related to the management in cervical cancer based on the results in published papers to date and the consensus of experts as a KSGO Consensus Statement., Competing Interests: Jae-Weon Kim, Myong Cheol Lim, Jeong-Yeol Park, and Seung-Hyuk Shim serve as editors of the Journal of Gynecologic Oncology (JGO), but have no role in the decision to publish this article. No other conflict of interest relevant to this article was reported., (Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Background: Debate on the value of lymphadenectomy continues in endometrial cancer. The aim of this study was to investigate patient and clinician preferences for routine lymphadenectomy versus no lymphadenectomy in the surgical management of endometrial cancer., Methods: A discrete choice experiment and trade-off question were designed and distributed to 103 endometrial cancer patients and 90 gynecologic oncologists. Participant preferences were quantified with regression analysis using scenarios based on three attributes: 5-year progression-free survival and the rates of acute and chronic complication. A trade-off technique varying the risk of recurrence for no lymphadenectomy was used to quantify any additional risk of recurrence that these participants would accept to receive no lymphadenectomy instead of routine lymphadenectomy., Results: On the basis of discrete choice experiment, the recurrence rate and lymphedema risk had a statistically significant impact on respondents' preference. The trade-off question showed that the median additional accepted risk of having no lymphadenectomy was 2.8% for gynecologic oncologists (0.5-14%) and 3.0% for patients (0.5-10%), but this difference was not significant (p = 0.620). Patients who were younger or had a higher education level or no history of delivery or shorter duration since diagnosis were prepared to accept higher additional risks of having no lymphadenectomy., Conclusions: Our results show that the majority of endometrial cancer patients and clinicians will accept a small amount of recurrence risk to reduce the incidence of lymphedema. Regarding preference heterogeneity among patients, our results show that it is important for surgeons to take a patient-tailored approach when discussing surgical management.

Study Objective: To measure and compare levels of extremely-low-frequency magnetic field (ELF-MF) exposure to surgeons during laparoscopic and robotic gynecologic surgeries., Design: Prospective case-control study., Design Classification: Canadian Task Force I., Setting: Gynecologic surgeries at the Yonsei University Health System in Seoul, Korea from July to October in 2014., Patients: Ten laparoscopic gynecologic surgeries and 10 robotic gynecologic surgeries., Intervention: The intensity of ELF-MF exposure to surgeons was measured every 4 seconds during 10 laparoscopic gynecologic surgeries and 10 robotic gynecologic surgeries using portable ELF-MF measuring devices with logging capability., Measurement and Main Results: The mean ELF-MF exposures were .1 ± .1 mG for laparoscopic gynecologic surgeries and .3 ± .1 mG for robotic gynecologic surgeries. ELF-MF exposure levels to surgeons during robotic gynecologic surgery were significantly higher than those during laparoscopic gynecologic surgery (p < .001) after adjustment for duration of measurement., Conclusion: The present study demonstrated low levels of ELF-MF exposure to surgeons during robotic gynecologic surgery and conventional laparoscopic surgery, hoping to alleviate concerns regarding the hazards of MF exposure posed to surgeons and hospital staff., (Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.)

The functions of many long non-coding RNAs (lncRNAs) in human cancers remain to be clarified. The lncRNA Hox transcript antisense intergenic RNA (HOTAIR) has been reported to reprogram chromatin organization and promote breast and colorectal cancer metastasis, the involvement of lncRNAs in cervical cancer is just beginning to be studied. In the present study, we examined the expression and the functional role of HOTAIR in cervical cancer. HOTAIR expression was determined in cervical cancer tissues (n=111) and corresponding normal tissues (n=40) by using real-time polymerase chain reaction, and its correlation with clinical parameters and prognosis were analyzed. To determine the effect of HOTAIR knockdown and overexpression in cervical cancer cell lines, we used the CCK-8 assay, wound healing migration and matrigel invasion assay. The expression level of HOTAIR in cervical cancer tissues was higher than that in corresponding non-cancerous tissues. High HOTAIR expression correlated with lymph node metastasis, and reduced overall survival. A multivariate analysis showed that HOTAIR was a prognostic factor for predicting cervical cancer recurrence. Knockdown of HOTAIR reduced cell proliferation, migration, and invasion in cervical cancer cell lines. Moreover, HOTAIR regulated the expression of vascular endothelial growth factor, matrix metalloproteinase-9 and epithelial-to-mesenchymal transition (EMT)-related genes, which are important for cell motility and metastasis. Therefore, HOTAIR may promote tumor aggressiveness through the upregulation of VEGF and MMP-9 and EMT-related genes. These findings indicate that HOTAIR may represent a novel biomarker for predicting recurrence and prognosis and serve as a promising therapeutic target in cervical cancer.

High-grade undifferentiated sarcomas (HGUSs) are rare uterine malignancies arising from the endometrial stroma. They are poorly differentiated sarcomas composed of cells that do not resemble proliferative-phase endometrial stroma. High-grade undifferentiated sarcomas are characterized by aggressive behavior and poor prognosis. Cyclin D1 has been reported as a diagnostic immunomarker for high-grade endometrial stromal sarcoma with an YWHAE-FAM22 rearrangement. YWHAE-FAM22 endometrial stromal sarcomas (ESS) represent a clinically aggressive subtype of ESS classified as high-grade endometrial sarcomas, and its distinction from the usual low-grade ESS with JAZF1 rearrangement and from HGUS with no identifiable molecular aberration may be important in guiding clinical management. Median age of the patients is between 55 and 60 years. The most common symptoms are vaginal bleeding, abdominal pain, and increasing abdominal girth.Disease is usually advanced with approximately 70% of the patients staged III to IV according to the International Federation of Gynecology and Obstetrics classification. Preferential metastatic locations include peritoneum, lungs, intra-abdominal lymph nodes, and bone. Median progression-free survival ranged from 7 to 10 months, and median overall survival ranged from 11 to 23 months. There is no clear prognostic factor identified for HGUS, not even stage. The standard management for HGUS consists of total hysterectomy and bilateral salpingo-oophorectomy. Systematic lymphadenectomy is not recommended. Adjuvant therapies, such as chemotherapy and radiotherapy, have to be discussed in multidisciplinary staff meetings.

Pancreatic adenocarcinoma up-regulated factor (PAUF) expression is elevated in both ovarian tumors and pancreatic adenocarcinoma. However, PAUF expression in ovarian tumors according to histologic subtype and grade has not been investigated. In this study, we examined various clinicopathologic features of 24 patients with mucinous cystadenoma (MCA), 36 with mucinous borderline tumors (MBTs), and 46 with mucinous adenocarcinomas (MACs) according to PAUF expression status assessed using immunohistochemistry. We found that MACs more frequently stained positive for PAUF than did MCAs and MBTs (P < 0.0001). Although there was no significant differences with respect to other clinicopathologic characteristics of MACs according to PAUF expression status, patients with PAUF-weakly positive and PAUF-strongly positive MACs tended to have a shorter overall survival (OS) than those with PAUF-negative MAC, determined using a Kaplan-Meier analysis (P = 0.1885). After adjusting for various clinicopathologic parameters, PAUF positivity of MACs was a significant predictive factor for disease-free survival (DFS) (negative vs. weakly positive: P = 0.045, hazard ratio [HR] = 57.406, 95% confidence interval [CI]: 1.090-3022.596; and negative vs. strongly positive: P = 0.034, HR = 97.890, 95% CI: 1.412-6785.925). In conclusion, PAUF was more frequently expressed in MAC than in its benign and borderline counterparts, and was associated with a poor OS and DFS in MAC patients. Therefore, we suggest that PAUF may be a practical biomarker for histopathological categorization and a prognostic marker for patients with an ovarian mucinous tumor.

Objective: We sought to perform a quantitative analysis on operative outcomes of laparoscopic staging surgery in patients with presumed early-stage ovarian cancer using a metaanalysis., Study Design: Electronic searches for studies of laparoscopic staging surgery in patients with ovarian cancer were performed within 3 electronic databases (Medline, Embase, and the Cochrane Library) using the key words "ovarian cancer," "early stage," "laparoscopy," "staging surgery," "staging laparoscopy," and "recurrence." Two authors independently screened articles, and those meeting the defined inclusion/exclusion criteria were included in the metaanalysis., Results: We identified 11 observational studies. The combined results of 3 retrospective studies showed that the estimated blood loss in laparoscopy was significantly lower than that for laparotomy (P < .001). The overall upstaging rate after laparoscopic surgery was 22.6% (95% confidence interval [CI], 18.1-27.9%) without significant heterogeneity among all study results. The overall incidence of conversion from laparoscopy to laparotomy was 3.7% (95% CI, 2.0-6.9%). The overall rate of recurrence in studies with a median follow-up period of ≥19 months was 9.9% (95% CI, 6.7-14.4%)., Conclusion: Through our quantitative analysis, we concluded that the operative outcomes of a laparoscopic approach in patients with early-stage ovarian cancer could be compatible with those of laparotomy. In the future, further randomized controlled trials may be needed., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: The aim of this study was to evaluate the use of single-port laparoscopic surgery in benign gynecologic diseases and to examine its impact on surgical outcomes., Methods: The medical records of 500 consecutive patients who underwent laparotomy or laparoscopic surgery performed by a single surgeon for benign disease from August 2008 to October 2010 were retrospectively reviewed., Results: The surgeries included hysterectomy (n = 239), adnexectomy (n = 212), and myomectomy (n = 51). The indications for surgery included adnexal lesions (48.1%), uterine fibroids (37.8%), preinvasive cervical disease (7.5%), and endometrial pathology (6.6%). Twenty-nine percent of the first 100 cases were single-port laparoscopic surgeries. The percentages increased in the second (62%), third (72%), fourth (71%), and last (86%) 100 cases. The percentages of laparotomy and multiport laparoscopy were 23% and 48%, respectively, in the first 100 cases; however, in the last 100 cases, the percentages dropped to 4% and 10%, respectively. A significant reduction in estimated blood loss and length of hospital stay was observed for all diseases. No differences were identified in the median operative time or complication rate over the study period., Conclusion: Single-port laparoscopic surgery can be applied to most benign gynecologic surgery without detrimental effects on clinical outcomes.

Background: This study aimed to compare single-port transumbilical total laparoscopic hysterectomy (SPLS-TLH) and four-port total laparoscopic hysterectomy (TLH) in terms of postoperative pain., Methods: The study enrolled 68 patients who underwent TLH from October 2009 to March 2010 and randomly assigned them to one of two groups. Patient demographics, operative outcomes, and postoperative pain were prospectively examined., Results: Four cases in the SPLS-TLH group were converted to other laparoscopic approaches. The two study groups did not differ in terms of patient demographics and surgical outcomes. Postoperative pain scores, measured using a visual analog scale, did not differ between the two groups. However, significantly higher total requests for analgesics were observed in the SPLS-TLH group (11.3 ± 4.1 vs. 7.7 ± 2.7; p < 0.001)., Conclusion: Compared with four-port TLH, SPLS-TLH is a feasible approach with comparable operative outcomes. However, reduction of postoperative pain is not evident with SPLS-TLH.

To identify specific proteins associated with chemotherapeutic responses, we analyzed protein expression patterns in stage IIIc primary serous epithelial ovarian cancer tissues displaying differential responses to first-line postoperative adjuvant chemotherapy. The expression profiles of five chemoresistant tissues [progression-free survival (PFS) ≤12 months] and five chemosensitive tissues (PFS ≥48 months) were analyzed with 2D electrophoresis, and the spot intensities of differentially expressed proteins were quantified. To validate these proteins as markers for chemoresistant disease, we analyzed tissues from an additional 17 patients. All the patients were allocated to the over- or underexpressing group according to protein spot intensity, and survival analysis was performed. In chemoresistant tissues, four proteins (thioredoxin domain containing four, similar to RIKEN cDNA 1700016G05, tubulin α 1A chain, and the pyruvate dehydrogenase E1-β subunit precursor) were overexpressed, and seven proteins [keratin 1, vitamin D-binding protein, creatine kinase B, annexin V, SH3-containing guanine nucleotide exchange factor (SGEF), tryptophan-aspartate repeat protein-1 (WDR 1), and WDR 1 isoform 1] were underexpressed. The underexpression of keratin 1, creatine kinase B, annexin V, SGEF, WDR1, and WDR1 isoform 1 were significantly correlated with poor overall survival. A combination of keratin 1 and SGEF showed the highest sensitivity of 0.800, specificity of 0.917, PPV of 0.800, and NPV of 0.917 in predicting chemoresistant disease. These proteins may be useful as predictive markers of chemoresistant disease. However, further analyses in large-scale should be performed before they can be considered reliable predictive markers of chemoresistant disease.

Purpose: Src is an attractive target because it is overexpressed in a number of malignancies, including ovarian cancer. However, the effect of Src silencing on other Src family kinases (SFKs) is not known. We hypothesized that other SFK members could compensate for the lack of Src activity., Experimental Design: Cell viability after either Src or Fgr silencing was examined in ovarian cancer cell lines by MTT assay. Expression of SFKs after Src silencing in ovarian cancer cells was examined by real-time reverse transcriptase (RT)-PCR. Therapeutic effect of in vivo Src and/or Fgr silencing was examined using siRNA incorporated into chitosan nanoparticles (siRNA/CH-NP). Microvessel density, cell proliferation, and apoptosis markers were determined by immunohistochemical staining in ovarian tumor tissues., Results: Src silencing enhanced cytotoxicity of docetaxel in both SKOV3ip1 and HeyA8 cells. In addition, Src silencing using siRNA/CH-NP in combination with docetaxel resulted in significant inhibition of tumor growth compared with control siRNA/CH-NP (81.8% reduction in SKOV3ip1, P = 0.017; 84.3% reduction in HeyA8, P < 0.005). These effects were mediated by decreased tumor cell proliferation and angiogenesis, and increased tumor cell apoptosis. Next, we assessed the effects of Src silencing on other SFK members in ovarian cancer cell lines. Src silencing resulted in significantly increased Fgr levels. Dual Src and Fgr silencing in vitro resulted in increased apoptosis that was mediated by increased caspase and AKT activity. In addition, dual silencing of Src and Fgr in vivo using siRNA/CH-NP resulted in the greatest reduction in tumor growth compared with silencing of either Src or Fgr alone in the HeyA8 model (68.8%, P < 0.05)., Conclusions: This study demonstrates that, in addition to Src, Fgr plays a biologically significant role in ovarian cancer growth and might represent an important target.

Objective: To reduce toxicities in cisplatin-based intraperitoneal (IP) chemotherapy, we substituted carboplatin for cisplatin. The purpose of this study was to provide preliminary toxicity data of carboplatin-based IP chemotherapy and to evaluate the feasibility of this chemotherapy regimen in patients with ovarian cancer after primary debulking surgery., Study Design: The toxicity data of 19 primary ovarian cancer patients (IP group) who underwent carboplatin-based IP and intravenous (IV) combination chemotherapy (IP carboplatin AUC 5 on day 1, IV paclitaxel 175mg/m² on day 2, and IP paclitaxel 60mg/m² on day 8) after primary debulking surgery were retrospectively analyzed and compared to 34 patients (IV group) who were treated with standard platinum-based IV chemotherapy during the same period., Results: The toxicity data in a total of 118 cycles were analyzed. Grade 3 or 4 leukopenia, neutropenia, and pain were more common in the IP group than the IV group. There were seven catheter-related complications. Fourteen patients (73.7%) were able to complete six cycles or more of IP chemotherapy. Survival results in the IP group were compared with those from the IV group; a prolonged progression-free survival was observed (26.6 vs. 20.7 months; p=0.038). Compared to the previous results with cisplatin-based IP chemotherapy, there was no significant difference in hematologic events. However, gastrointestinal, neurologic, and metabolic events in this study were definitely lower compared to those of cisplatin-based IP chemotherapy., Conclusions: Carboplatin-based IP and IV combination chemotherapy is feasible in patients with ovarian carcinoma after primary debulking surgery., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: The purpose of the present study is to demonstrate the feasibility of single-port transumbilical laparoscopic surgery (SPLS) for hysterectomy and elaborate on our experience in order to introduce the single-port approach for gynecologic surgery., Methods: Between August 2008 and February 2009, 30 patients who initially planned to undergo single-port laparoscopic surgery at Yonsei University Health System in Seoul, Korea were enrolled in this study. The authors used a single-port three-channel system with a wound retractor, surgical gloves, and one 10/11-mm and two 5-mm trocars. All surgical procedures were performed with 30 degrees , 5-mm laparoscope, conventional laparoscopic instruments, and the LigaSure system (Valleylab, Boulder, CO, USA). Patient characteristics and surgical outcomes were prospectively evaluated. A visual analog score (VAS) scale was used to measure postoperative pain., Results: Twenty-nine of 30 patients underwent single-port laparoscopic surgery without conversion to laparotomy or conventional laparoscopic hysterectomy. Median operative time was 100 min (57-155 min), median blood loss was 100 ml (10-400 ml), median postoperative hospital stay was 3 days (2-6 days), and median weight of resected uteri was 167 g (45-482 g). VAS scoring of pain at 6, 24, and 48 h after surgery was 4, 3, and 2, respectively. There were no operative complications., Conclusion: SPLS is a feasible approach for hysterectomy in terms of operative time, complication rates, and cosmetic results. However, the possible benefits for patients such as better cosmetic outcomes, reduced pain, and lower complication rates should be evaluated in randomized prospective studies.