Lugol's Solution Reduces Positive Margins and Residual Disease After the Large Loop Excision of Transformation Zone.

OBJECTIVE: This study aimed to examine whether the intraoperative use of Lugol's solution reduces the proportion of positive resection margins (RMs) using the data of women who underwent large loop excision of the transformation zone (LLETZ). MATERIALS AND METHODS: A total of 1,751 consecutive women with cervical intraepithelial neoplasia (CIN) who underwent LLETZ with or without Lugol's solution were retrospectively retrieved from each database of 3 university hospitals in South Korea. Outcomes included positive RMs and residual disease pathologically confirmed within 6 months after LLETZ. RESULTS: Positive RMs were noted in 345 cases (19.7%). Among 1,507 women followed up, residual disease was diagnosed in 100 cases (6.6%) (69/308 cases with positive RMs; 31/1,199 cases with negative RMs). The Lugol's solution group was less likely to have positive RMs (11.8% vs 25.5%, p < .01), to require additional surgical intervention (5.4% vs 10.2%, p < .01), and to have residual disease (4.9% vs 8.0%, p = .02). On multiple logistic regression analysis, Lugol's solution reduced the proportion of positive RMs (adjusted odds ratio [aOR], 0.31). Age (50 years or older; aOR, 1.64), preconization cervical cytology (aOR, 1.53), high-risk human papillomavirus (aOR, 1.75), and CIN 2 or 3 (aOR, 2.65) were independent risk factors for margin positivity ( p < .01 for all except high-risk human papillomavirus of p = .05). CONCLUSIONS: Lugol's solution optimizes CIN treatment by reducing the proportion of positive RMs and residual disease after LLETZ.

Reduction of cycles of neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian or primary peritoneal cancer (ROCOCO): study protocol for a phase III randomized controlled trial.

BACKGROUND: Primary debulking surgery (PDS) and adjuvant chemotherapy is the standard treatment for advanced ovarian, fallopian or primary peritoneal cancer. However, neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) has been introduced as an alternative, showing similar efficacy and decreased postoperative complications compared with PDS. Although there is still no evidence for whether three or four cycles of NAC used clinically could be adequate, reducing one cycle of NAC is expected to remove more visible tumours and thereby improve prognosis. Thus, we proposed with this study to evaluate the efficacy and safety of reducing one cycle of NAC for advanced ovarian, fallopian or primary peritoneal cancer. METHODS: This study is a prospective, multi-centre, open-label, randomized phase III trial. A total of 298 patients with advanced ovarian, fallopian or primary peritoneal cancer will be recruited and randomly assigned to either three (control group) or two cycles of NAC (experimental group). After the NAC, we will conduct IDS with maximal cytoreduction and then administer the remaining three or four cycles for a total of six cycles of adjuvant chemotherapy. The primary end point is progression-free survival, and the secondary end points are time to tumour progression, overall survival, tumour response after NAC, IDS and adjuvant chemotherapy, radiologic investigation after IDS, tumour response by positron emission tomography-computed tomography after NAC, quality of life, adverse events, success rate of optimal cytoreduction, surgical complexity, postoperative complications and safety of IDS. We will assess these factors at screening, at every cycle of chemotherapy, at IDS, after the completion of chemotherapy, every 3 months for the first 2 years after the planned treatment and every 6 months thereafter for 3 years. DISCUSSION: We hypothesize that reducing one cycle of NAC will contribute to more resection of visible tumours despite 10% reduction of optimal cytoreduction, which could improve survival. Moreover, two cycles of NAC may increase postoperative complications by 5% compared with three cycles, which may be acceptable. TRIAL REGISTRATION: This study has been prospectively registered at ClinicalTrials.gov on Oct. 2nd, 2018 (NCT03693248, URL: https://clinicaltrials.gov/ct2/show/NCT03693248).

Anti-N-methyl-D-aspartate Receptor Encephalitis: a Rare Complication of Ovarian Teratoma.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a potentially life-threatening but reversible autoimmune disorder characterized by psychiatric symptoms, cognitive dysfunction, speech dysfunction, seizures, movement disorder, decreased level of consciousness, and autonomic dysfunction or central hypoventilation. It occurs predominantly in young women and approximately half of them have underlying tumors, mainly ovarian teratoma. A 24-year old woman was admitted because of fever, headache, abnormal movement and decreased mental status. Five cycles of plasmapheresis improved her neurological and mental status. Anti-NMDAR antibodies in her CSF and serum were positive, and computed tomography revealed a 1-cm sized mass suggestive of mature cystic teratoma arising from the right ovary. We promptly performed laparoscopic right ovarian cystectomy. She was discharged after 2 weeks with mild memory deficit. Prompt removal of ovarian teratoma and multidisciplinary care are particularly important for good outcome.

Laparoscopic management is feasible for nonobstetric surgical disease in all trimesters of pregnancy.

BACKGROUND: Nonobstetric surgical interventions are required in some women during pregnancy. The most common nonobstetric conditions requiring surgery during pregnancy are acute appendicitis and cholecystitis. This study aimed to evaluate pregnancy outcomes and complications following surgical procedures for presumed nonobstetric surgical interventions during pregnancy, and to compare the outcomes between the laparoscopic and open approaches. METHODS: We conducted a retrospective study of patients who underwent laparoscopic or open surgery during pregnancy for nonobstetric surgical indications at our institution between 2008 and 2016. RESULTS: A total of 62 consecutive patients who underwent surgical intervention due to nonobstetric causes during pregnancy were included in our study. Of these, 35 (56.5%) were managed with laparoscopy and 27 (43.5%) with the open approach. Patients who underwent laparoscopy had a significantly shorter hospital stay and lower pain score on postoperative day 2 than those who underwent open surgery (5.5 vs. 7.2 days, p = 0.03 and 1.4 vs. 2.4, p < 0.01, respectively). There were no significant differences in operative complications between both groups. In advanced pregnancy (gestational age ≥ 23 weeks), 7 patients (41.2%) were managed with laparoscopy and 10 (58.8%) with the open approach. No differences in surgical complications were found between both groups in advanced pregnancy as well. CONCLUSIONS: In our study, laparoscopic surgery was found to be feasible and safe in the late second and third trimesters as well as in the first and early second trimesters without adverse effects on pregnancy.

Platelet-derived growth factor receptor alpha (PDGFRα) targeting and relevant biomarkers in ovarian carcinoma.

OBJECTIVE: Platelet-derived growth factor receptor alpha (PDGFRα) is believed to be associated with cell survival. We examined (i) whether PDGFRα blockade enhances the antitumor activity of taxanes in ovarian carcinoma and (ii) potential biomarkers of response to anti-PDGFRα therapy. METHODS: PDGFRα expression in 176 ovarian carcinomas was evaluated with tissue microarray and correlated to survival outcome. Human-specific monoclonal antibody to PDGFRα (IMC-3G3) was used for in vitro and in vivo experiments with or without docetaxel. Gene microarrays and reverse-phase protein arrays with pathway analyses were performed to identify potential predictive biomarkers. RESULTS: When compared to low or no PDGFRα expression, increased PDGFRα expression was associated with significantly poorer overall survival of patients with ovarian cancer (P=0.014). Although treatment with IMC-3G3 alone did not affect cell viability or increase apoptosis, concurrent use of IMC-3G3 with docetaxel significantly enhanced sensitization to docetaxel and apoptosis. In an orthotopic mouse model, IMC-3G3 monotherapy had no significant antitumor effects in SKOV3-ip1 (low PDGFRα expression), but showed significant antitumor effects in HeyA8-MDR (high PDGFRα expression). Concurrent use of IMC-3G3 with docetaxel, compared with use of docetaxel alone, significantly reduced tumor weight in all tested cell lines. In protein ontology, the EGFR and AKT pathways were downregulated by IMC-3G3 therapy. MAPK and CCNB1 were downregulated only in the HeyA8-MDR model. CONCLUSION: These data identify IMC-3G3 as an attractive therapeutic strategy and identify potential predictive markers for further development.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Overexpression of enhancer of zeste homolog 2 (EZH2) and focal adhesion kinase (FAK) in high grade endometrial carcinoma.

OBJECTIVE: The deregulation of E-cadherin is associated with Src/FAK signaling axis and histone deacetylase (HDAC)/EZH2 activity. However, the association between EZH2 and FAK and its clinical significance in endometrial carcinoma has not been reported. METHODS: 202 archived cases of endometrial carcinoma (1996-2000) were reviewed and divided into two subtypes. TMAs were developed as per established procedures. EZH2, FAK, and pFAK immunohistochemical stains were performed and the expression was scored as negative (0), low (1) and high (2). Proper statistical analysis was used to assess the correlation between the expression profiles and the clinicopathological parameters and clinical outcome. RESULTS: A total of 141 (69.8%) type-1 tumors and 61 (30.2%) type-2 tumors were identified. EZH2 overexpression was identified in 7.6% of type-1 tumors vs. 63% of type-2 tumors (p<0.001). FAK and pFAK overexpression was only seen in 24.8% and 1.7% of Type-1 tumors as compared to 72% and 58.8% of type-2 tumors, respectively (p<0.001). A positive correlation between the expression of EZH2, FAK, pFAK and PTEN (p<0.0001) was found. The overexpression of EZH2, FAK, and pFAK were significantly associated with high histologic grade, angiolymphatic invasion, lymph node metastasis, myometrial invasion and cervical involvement (p<0.01). Kaplan-Meier analysis demonstrates that the overexpression of EZH2 (p=0.0024), FAK and pFAK (p=0.0001) was significantly associated with decreased overall survival. CONCLUSION: The overexpression of EZH2, FAK and pFAK correlates with well established pathologic risk factors and may predict a more aggressive biologic behavior in endometrial carcinoma, transforming these proteins into potential therapeutic targets for treatment of endometrial cancer.

Clinical efficacy of a novel method of fertility-preserving adenomyomectomy in infertile women with diffuse adenomyosis.

Beneficial and detrimental effect of surgical adenomyomectomy is still controversial in infertile women with severely diffuse adenomyosis. The primary objective of this study was to assess whether a novel method of fertility-preserving adenomyomectomy could improve pregnancy rates. The secondary objective was to evaluate whether it could improve dysmenorrhea and menorrhagia symptoms in infertile patients with severe adenomyosis. A prospective clinical trial was conducted between December 2007 and September 2016. Fifty women with infertility due to adenomyosis were enrolled in this study after clinical assessments by infertility experts. A novel method of fertility-preserving adenomyomectomy was performed on 45 of 50 patients. The procedure included T- or transverse H-incision of the uterine serosa followed by preparation of the serosal flap, excision of the adenomyotic tissue using argon laser under ultrasonographic monitoring, and a novel technique of suturing between the residual myometrium and serosal flap. After the adenomyomectomy, the changes in the amount of menstrual blood, relief of dysmenorrhea, pregnancy outcomes, clinical characteristics, and surgical features were recorded and analyzed. All patients obtained dysmenorrhea relief 6 months postoperatively (numeric rating scale [NRS]; 7.28 ±â€…2.30 vs 1.56 ±â€…1.30, P < .001). The amount of menstrual blood decreased significantly (140.44 ±â€…91.68 vs 66.33 ±â€…65.85 mL, P < .05). Of the 33 patients who attempted pregnancy postoperatively, 18 (54.5%) conceived either by natural means, in vitro fertilization and embryo transfer (IVF-ET), or thawing embryo transfer. Miscarriage occurred in 8 patients, while 10 (30.3%) had viable pregnancies. This novel method of adenomyomectomy resulted in improved pregnancy rates, as well as relief of dysmenorrhea and menorrhagia. This operation is effective in preserving fertility potential in infertile women with diffuse adenomyosis.

Incidence and survival of gynecologic cancer including cervical, uterine, ovarian, vaginal, vulvar cancer and gestational trophoblastic neoplasia in Korea, 1999-2019: Korea Central Cancer Registry.

OBJECTIVE: To investigate the incidence, trends, and survival rates of all gynecologic cancers using the Korea Central Cancer Registry (KCCR) database from 1999-2019. METHODS: Gynecologic cancer data were obtained from the KCCR database between 1999 and 2019. Age-standardized incidence rates (ASRs), annual percentage changes, and average annual percentage changes (AAPCs) were calculated. The relative survival rate (RSR) was reported by age group, stage, and 6-year period (I: 1999-2005, II: 2006-2012, III: 2013- 2019). RESULTS: The gynecologic cancer ASRs were 26.2 and 24.9 per 100,000 individuals in 1999 and 2019, respectively. Trends of incidence in gynecologic cancer revealed a decrease in cervical cancer and gestational trophoblastic neoplasia (GTN) with AAPCs of -3.4 and -4.3, respectively. Conversely, the incidence of uterine, ovarian, and vulvar cancers increased with AAPCs of 4.7, 2.3, and 2.1, respectively. AAPC for vaginal cancer showed no change. The 5-year survival rate was highest for GTN (90.5%) and lowest for vaginal cancer (56.6%). An increase in age was correlated with poorer survival rates across all gynecologic cancers, excluding vaginal cancer. For all gynecologic cancer types, the prognosis deteriorates with advancing cancer stages. The RSR of uterine cancer improved consistently across all periods. The ovarian cancer RSR improved more in period III than in periods I or II. Additionally, the vulvar cancer RSR improved more in periods II and III than in period I. CONCLUSION: In Korea, the incidence of cervical cancer and GTN decreased, whereas the incidence of uterine, ovarian, and vulvar cancer increased from 1999 to 2019. The RSR for uterine, ovarian, and vulvar cancers showed consistent improvements over different periods. Effective screening programs and the adoption of advanced treatments may be necessary to further reduce the burden of gynecologic cancer.

Human papillomavirus genotypes and cofactors causing cervical intraepithelial neoplasia and cervical cancer in Korean women.

OBJECTIVE: Infection with human papillomavirus (HPV) is a necessary cause of cervical cancer, but the risk associated with the various viral types and related cofactors have not been adequately assessed in Korean women. This study aimed to investigate the genotype distribution of HPV and cofactors related to cervical carcinogenesis in Korean women. MATERIALS AND METHODS: We conducted a hospital-based case-control study in 215 women with histologically confirmed cervical neoplasia (111 cases of cervical intraepithelial neoplasia [CIN] and 104 cases of invasive cervical cancer [ICC]) and 1214 healthy control women. Polymerase chain reaction-based dot blot assays were used for detection of 16 high-risk HPV types. To clarify the cofactors, we administered questionnaires evaluating smoking, drinking, and sexual and reproductive history from women infected with HPV. RESULTS: Human papillomavirus was detected in 86.5% of the women with CIN and 96.2% of the women with ICC compared to 14.6% of the control women. The most common HPV types were, in descending order of frequency, types 16, 58, 18, 33, and 66 for CIN, and types 16, 18, 31, and 33 for ICC. Among the control women, HPV 16, 66, 33, 58, 18, and 31 were the most common types. Smoking and higher number of births (≥3) were associated with CIN (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.21-5.15, and OR, 2.67; 95% CI, 1.36-5.28, respectively). This relationship was also found in the women with ICC (OR, 3.42; 95% CI, 1.59-7.38, and OR, 2.17; 95% CI, 1.08-4.38, respectively) compared to controls. In addition, the circumcision of sexual partner and the sexual habit of condom use were protective factors for ICC (OR, 0.47; 95% CI, 0.24-0.90, and OR, 0.19; 95% CI, 0.06-0.57, respectively). CONCLUSION: Human papillomavirus types 16, 18, 31, 33, and 58 are the major causative genotypes for cervical carcinogenesis in Korean women. Smoking and multiparity seem to be the most significant cofactors.

Cyclooxygenase-2 is an independent predictor of poor prognosis in uterine leiomyosarcomas.

INTRODUCTION: Cyclooxygenase-2 (COX-2) is a well-known enzyme that promotes tumor growth and metastasis. Cyclooxygenase-2 is upregulated in a number of human epithelial tumors, but data about the significance of COX-2 in mesenchymal tumors are lacking. The purpose of this study was to determine COX-2 expression in uterine sarcomas and whether a relationship exists between COX-2 expression and clinicopathologic outcomes. METHODS: Immunohistochemical staining for COX-2 was performed on paraffin-embedded tissue blocks of 49 uterine sarcomas (30 leiomyosarcomas, 14 endometrial stromal sarcomas, and 5 carcinosarcomas). Positive staining was defined as moderate or strong staining in 5% or more of tumor cells. RESULTS: Four of 30 leiomyosarcomas, 1 of 14 endometrial stromal sarcomas, and 2 of 5 carcinosarcomas were positive for COX-2 expression. In leiomyosarcomas, COX-2 expression correlated with tumor stage with marginal significance (P = 0.058). Patients with leiomyosarcoma positive for COX-2 expression had a lower overall survival rate than those without COX-2 expression (P = 0.025). In the multivariate Cox proportional hazards regression model, COX-2 expression, tumor stage, and mitotic count were independently associated with overall survival in leiomyosarcomas. CONCLUSIONS: Our data suggest that immunohistochemically determined COX-2 expression is an independent prognostic factor in uterine leiomyosarcomas. Assessment of COX-2 status might be useful for determining the prognosis in patients with uterine leiomyosarcomas.

Diastolic forward flow in the fetal main pulmonary artery and its implication for fetal cardiac cycle evaluation.

OBJECTIVES: To examine if the fetal main pulmonary artery diastolic forward flows (MPADFs) are detected consistently, if the waves from fetal MPADFs coincide with those from atrial contractions, and the reproducibility of the cardiac cycle measurements using this technique. METHODS: Two examiners performed a fetal pulsed Doppler echocardiography of the four chamber (4CV), ductal arch (DA) and short axis (SA) views on 44 women with singleton pregnancies. Time intervals between atrial contraction peaks and those between MPADF peaks were compared. Atrioventricular (AV) and ventriculoatrial (VA) intervals were measured from MPADF waves in DA and SA views and compared between observers. Intraclass correlation coefficients (ICCs) were calculated as a measure of inter-observer reproducibility. RESULTS: In all observations, MPADFs were demonstrated. The mean time intervals between atrial contraction peaks from 4CV and those between MPADF peaks from DA and SA views were not significantly different. The mean AV and VA intervals were not significantly different between observers. Comparison of measurements of two observers had substantial agreements. CONCLUSIONS: Our data show that MPADFs can be found consistently and coincide with atrial contractions. As cardiac cycle measurements can be done with considerable reproducibility, this technique may be useful in assessing fetal cardiac cycle.

P53 codon 72 and p21 codon 31 polymorphisms and susceptibility to cervical adenocarcinoma in Korean women.

The aims of this study were to evaluate the genotype frequencies of p53 codon 72 and p21 codon 31 in cervical adenocarcinoma patients and controls, and the association between the specific genotype or genotype combination of these polymorphisms and the risk of cervical adenocarcinoma in Korean women. Genotyping was performed using DNA from cervical biopsy specimens collected from 53 patients with cervical adenocarcinoma, of whom 34 were HPV 16 or 18 positive, and from the cervical exfoliated cells from 286 control women, of whom 48 were positive for HPV 16 or 18. For the determination of p53 polymorphisms genomic DNA was examined by PCR amplification of the specific allele assay, and for the determination of p21 polymorphisms DNA was examined by the PCR-RFLP assay using BsmAI. We found significant differences in genotype frequencies of both genes between the two groups (p < 0.001). The p53 genotypes containing the Pro allele were significantly associated with cervical adenocarcinoma with an OR of 2.89 (95% CI 1.54-5.42). Also, homozygous carriers of the p21 Ser allele showed a substantially increased risk of developing cervical adenocarcinoma (OR 2.07; 95% CI 1.13-3.79) compared to genotypes containing the Arg allele. In addition, the combination of the Pro allele containing genotypes of p53 and the Ser homozygous genotype of p21 posed a remarkably increased risk (OR 5.22; 95% CI 2.24-12.16), although the interaction of the two genes could not be found. These significant differences were intensified in groups with high-risk HPV infection (types 16 or 18).

Comparison of diagnostic accuracy between endometrial curettage and aspiration biopsy in patients treated with progestin for endometrial hyperplasia: a Korean Gynecologic Oncology Group study.

OBJECTIVE: To compare the diagnostic accuracy of dilatation and curettage (D&C) versus endometrial aspiration biopsy in follow-up evaluation of patients treated with progestin for endometrial hyperplasia (EH). METHODS: A prospective multicenter study was conducted from 2015 to 2018. Patients with EH were treated with progestin, one of the following three treatment regimens: oral medroxyprogesterone acetate (MPA) 10 mg/day for 14 days per cycle, continuous MPA 10 mg/day or the levonorgestrel-releasing intrauterine system (LNG-IUS). At 3 or 6 months of treatment, endometrial tissues were obtained via 2 methods in each patient: aspiration biopsy, followed by D&C. The primary outcome was the consistency of the histologic results between the 2 methods. The secondary outcome was the regression rate at 6 months of treatment. RESULTS: The study population comprised 65 patients (55 with non-atypical hyperplasia, 10 with atypical hyperplasia). During the follow-up, a comparison of the pathologic results from aspiration biopsy and D&C was carried out for the 65 cases. Thirty-eight cases were diagnosed as EH by D&C. Among these, only 24 were diagnosed with EH from aspiration biopsy, for a diagnostic concordance of 63.2% (κ=0.59). Forty-four patients were followed up at 6 months, and the regression rate was 31.8% (14/44). Responses were obtained for 41.7% (5/12) of the cyclic MPA group, 58.3% (7/12) of the continuous MPA group and 10% (2/20) of the LNG-IUS group. CONCLUSION: As a follow-up evaluation of patients treated with progestin for EH, aspiration biopsy is less accurate than D&C and might not be a reliable method. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02412072.

Type-Specific Viral Load and Physical State of HPV Type 16, 18, and 58 as Diagnostic Biomarkers for High-Grade Squamous Intraepithelial Lesions or Cervical Cancer.

PURPOSE: High rate of false-positive tests is a major obstacle to use human papillomavirus (HPV) detection as a diagnostic tool for high-grade squamous intraepithelial lesions or cervical cancer (HSIL+). We investigated whether type-specific viral load or physical state of HPV 16, 18, and 58 are useful biomarkers for HSIL+. MATERIALS AND METHODS: Type-specific viral loads of E6 and E2 genes in cervical cells from 240, 83, and 79 HPV 16-, 18-, and 58-infected women, respectively, were determined using real-time polymerase chain reaction. Viral loads were normalized to cellular DNA (copy/cell). Total and integrated viral loads and physical state were compared between HSIL+ and controls, and diagnostic value was determined using receiver operating characteristic analysis. RESULTS: Viral loads of HPV 16, 18, and 58 were significantly different in lesions in the same pathologic grade. High type-specific total viral loads were significantly associated with HSIL+ (odds ratio [OR], 14.065, 39.472, and 7.103 for HPV 16, 18, and 58, respectively). High integrated viral load was related to HSIL+ in women with HPV 16 (OR, 8.242), and integrated state was associated with HSIL+ in women with HPV 18 (OR, 9.443). Type-specific total viral load was significantly associated with HSIL+ (area under curve, 0.914, 0.937, and 0.971 for HPV 16, 18, and 58, respectively), indicating an excellent performance in detecting HSIL+. CONCLUSION: Type-specific total viral load may be a powerful diagnostic marker for HSIL+ in HPV 16-, 18-, and 58-infected HSIL+ lesions. If demonstrated in all other high-risk HPV types, this method can lead to a paradigm shift in the strategy of equivocal cytologic abnormalities.

Safety and Effectiveness of Dienogest (Visanne®) for Treatment of Endometriosis: A Large Prospective Cohort Study.

Dienogest (DNG) is a progestin with highly selective progesterone activity and known to be effective in the treatment of endometriosis. This prospective cohort study in patients who had been treated with DNG 2 mg (Visanne®) for endometriosis was conducted to assess the safety and effectiveness of DNG in a large Korean cohort. This study included 3356 patients with endometriosis from 73 centers in Korea. All patients were treated with DNG 2 mg daily and were followed up for at least 6 months after initial visit. Any adverse events were recorded including severity, onset/closing date, outcomes, treatments, and the causality with DNG. Effectiveness of DNG was measured by changes in visual analogue scale (VAS) from baseline at the end of follow-up. The mean age of the subjects was 34.96 years, and the mean duration of treatment was 285.44 days. Incidence of adverse drug reaction (ADR) was 13.27% (413/3113). The most frequently reported ADR were "abnormal uterine bleeding" 4.14% (129/3113), "increased weight" 2.57% (80/3113), and "headache" 1.22% (38/3113). The number of patients (%) with favorable bleeding patterns was observed to increase as the duration of treatment increases. Amenorrhea was observed in 29.63%, 41.25%, 46.26%, and 53.20% of patients at 3 months, 6 months, 12 months, and more than 12 months follow-up period, respectively. The mean (±SD) VAS change from baseline at the last follow-up visit was -28.19 ± 28.39 mm (P value < 0.0001). This large cohort study confirms, in routine clinical practice, that DNG is safe and effective for treatment of endometriosis.

Clinical and biological significance of EZH2 expression in endometrial cancer.

The objective of this study was to examine the clinical significance of EZH2 expression and the therapeutic efficacy of its silencing in endometrial cancer. EZH2 expression in clinical samples was evaluated using a tissue microarray and correlated with clinical outcomes. The biological roles of EZH2 were assayed in vitro and in vivo. Gene expression was examined to reveal the molecular mechanism underlying the roles of EZH2 in endometrial cancer. We found that EZH2 overexpression was significantly correlated with disease-free and overall survival of patients with endometrial cancer. EZH2 silencing resulted in decreased cell viability and invasiveness, and increased apoptosis. In addition, EZH2 silencing enhanced the cytotoxicity of taxanes and cisplatin in Hec-1A and Ishikawa endometrial cancer cells. EZH2 silencing using small-interfering RNA (siRNA) incorporated into chitosan nanoparticles (siRNA/CN) induced a significant anti-tumor effect compared with that observed in controls (66.6% reduction in Hec-1A cells and 63.2% reduction in Ishikawa cells, p < .05 for both). Moreover, EZH2 siRNA/CN in combination with taxanes produced more robust anti-tumor effects versus those induced by monotherapies (77.0% for Hec-1A cells and 57.7% for Ishikawa cells, p < .05 for both). These results were associated with decreased angiogenesis and cell proliferation, and enhanced apoptosis. Genomic analyses revealed that EZH2 silencing decreased the expression levels of many genes associated with tumor growth, including PRDX6. Collectively, these results support EZH2 as an attractive target for the therapeutic management of endometrial cancer.

Practice guidelines for management of ovarian cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement.

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.

Successful twin pregnancy after vaginal radical trachelectomy using transabdominal cervicoisthmic cerclage.

The outcome of vaginal radical trachelectomy (VRT) for the management of early cervical cancer is comparable to that achieved with radical hysterectomy. Although VRT preserves the potential for pregnancy, the outcome of twin pregnancies following VRT is poor. We report a successful twin pregnancy after VRT using transabdominal cervicoisthmic cerclage.

Estrogen-induced acute pancreatitis: A case report and literature review.

Estrogens are commonly used in gynecologic area, such as oral contraception, hormone replacement therapy, and in vitro fertilization-embryo transfer. Although estrogen is a common cause of acute drug-induced pancreatitis, there has been paucity of report in Korea. Clinical course of estrogen-induced acute pancreatitis is usually mild to moderate, but fetal case can occur. In addition, there can be a latency from the first administration to the symptom. Therefore, physicians should consider the possibility of the disease when a woman taking estrogen or previous history of taking estrogen presents with acute abdominal pain. Here, we report a case of estrogen-induced acute pancreatitis that occurred during the preparation for embryo transfer.