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Introduction: Stage IB (deep myometrial invasion) high‐grade endometrioid adenocarcinoma (EA), regardless of LVSI status, is classified into high‐intermediate risk groups, requiring surgical lymph node staging. Intraoperative frozen section (IFS) is commonly used, but its adequacy and reliability vary between reports. Hence, we determined the utility of IFS in identification of high‐risk factors, including deep myometrial invasion and high‐grade. Method: We retrospectively analyzed 9,985 cases operated with hysterectomy and diagnosed with FIGO stage I/II EA in postoperative paraffin section (PS) results at 30 Chinese hospitals from 2000 to 2019. We determined diagnostic performance of IFS and investigated whether the addition of IFS to preoperative biopsy and imaging could improve identification of high‐risk factors. Results: IFS and postoperative PS presented the highest concordance in assessing deep myometrial invasion (Kappa: 0.834), followed by intraoperative gross examination (IGE Kappa: 0.643), MRI (Kappa: 0.395), and CT (Kappa: 0.207). IFS and postoperative PS presented the highest concordance for high‐grade EA (Kappa: 0.585) compared to diagnostic curettage (D&C 0.226) and hysteroscope (Hys 0.180). Sensitivity and specificity for detecting deep myometrial invasion were 86.21 and 97.20% for IFS versus 51.72 and 88.81% for MRI, 68.97 and 94.41% for IGE. These figures for detecting high‐grade EA were 58.21 and 96.50% for IFS versus 16.42 and 98.83% for D&C, 13.43 and 98.64% for Hys. Parallel strategies, including MRI‐IFS (Kappa: 0.626), D&C‐IFS (Kappa: 0.595), and Hys‐IFS (Kappa: 0.578) improved the diagnostic efficiencies of individual preoperative examinations. Based on the high sensitivity of IFS, parallel strategies improved the sensitivities of preoperative examinations to 89.66% (MRI), 64.18% (D&C), 62.69% (Hys), respectively, and these differences were statistically significant (p = 0.000). Conclusion: IFS presented reasonable agreement rates predicting postoperative PS results, including deep myometrial invasion and high‐grade. IFS helps identify high‐intermediate risk patients in preoperative biopsy and MRI and guides intraoperative lymphadenectomy decisions in EA. [ABSTRACT FROM AUTHOR]

Purpose: Follow-up and immunosuppressive medication (ISM) adherence are both important for kidney transplant recipients postoperatively and whether follow-up factors affect the ISM adherence remains unclear. The aim of this study was to examine the relationship between follow-up factors and ISM adherence, and the factors associated with ISM adherence. Patients and Methods: An internet-based cross-sectional survey was conducted in a single kidney transplant center in China. The participants completed the internet-based questionnaire and the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS©) from January 12 to January 26, 2021. Results: Finally, 288 (66.7%) participants responded to this survey. The percentage of full adherence to immunosuppressant was 51.7% (149/288), with 33.3% of the participants reporting a problem in timing dimension. We found that follow-up with a fixed doctor was significantly positive to good adherence (OR=2.124, 95% CI=1.111– 4.062, P=0.023) after analyzing the survey data. Time since kidney transplantation and number of non-immunosuppressants were both associated with immunosuppressant adherence. No significant difference was found regarding the effect of the follow-up adherence on ISM adherence. Conclusion: Our study demonstrated an insufficient prevalence of adherence to immunosuppressant in Chinese renal transplant recipients and revealed that follow-up with a fixed doctor may be a way to improve the patients' ISM adherence. This anonymous internet-based survey provides valuable insight into the actual adherence rate, factors associated with non-adherence, and situations that may improve medication-taking. [ABSTRACT FROM AUTHOR]

Background: Active targeted case-finding is a cost-effective way to identify individuals with high-risk for early diagnosis and interventions of chronic obstructive pulmonary disease (COPD). A precise and practical COPD screening instrument is needed in health care settings. Methods: We created four statistical learning models to predict the risk of COPD using a multi-center randomized cross-sectional survey database (n = 5281). The minimal set of predictors and the best statistical learning model in identifying individuals with airway obstruction were selected to construct a new case-finding questionnaire. We validated its performance in a prospective cohort (n = 958) and compared it with three previously reported case-finding instruments. Results: A set of seven predictors was selected from 643 variables, including age, morning productive cough, wheeze, years of smoking cessation, gender, job, and pack-year of smoking. In four statistical learning models, generalized additive model model had the highest area under curve (AUC) value both on the developing cross-sectional data set (AUC = 0.813) and the prospective validation data set (AUC = 0.880). Our questionnaire outperforms the other three tools on the cross-sectional validation data set. Conclusions: We developed a COPD case-finding questionnaire, which is an efficient and cost-effective tool for identifying high-risk population of COPD. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of five methods including the ThinPrep cytological test (TCT), liquid-based cytology, the human papillomavirus (HPV) test, detection of the TERC and C-MYC genes and visual inspection with acetic acid/Lugol's iodine (VIA/VILI) for opportunistic cervical cancer screening, and to explore whether genomic amplification of the human telomerase gene and C-MYC in liquid-based cytological specimens can be used as a method for opportunistic cervical cancer screening.Methods: Data were collected prospectively from 1,010 consecutive patients who visited the gynecology clinic and agreed to participate in opportunistic cervical cancer screening at our institution from November 2010 to July 2011. The five methods mentioned above were used for the screening in all cases. The histopathological diagnosis served as the gold standard for the evaluation. A comparison between the five screening methods for the diagnosis of high-grade cervical intraepithelial neoplasia (CIN II and III) was performed for their sensitivity, specificity, false-positive rate, false-negative rate, accuracy rate, positive likelihood ratio and negative likelihood ratio. A comprehensive comparison of the different combination programs for screening was performed according to the analysis of the receiver operating characteristic (ROC) curve area. The accuracy of the five screening methods for the diagnosis of high-grade CIN (CIN II and III) was compared in the different age groups. A joint model for the diagnosis using different combinations of the five methods was developed according to the analysis by the SAS 8.0 software. The model was used to evaluate the accuracy of the different combination programs for the diagnosis of high-grade CIN, and the results were confirmed by the histopathological examination.Results: The sensitivity and specificity of the single screen method (TCT, HPV test, detection of the TERC and C-MYC genes, and VIA/VILI method) for CIN II was 80.9, 70.2, 72.3, 76.6, and 72.3%, as well as 98.0, 95.1, 96.3, 96.3, and 90.4%, respectively. The sensitivity of the single screening method in four different age groups (25-34, 35-44, 45-54 and 55-66 years) was as follows: TCT, 64.3, 90.9 76.5, and 85.7%; HPV test, 78.6, 72.7, 60.0, and 71.4%; the TERC gene, 50.0, 90.9, 80.0, and 71.4%; the C-MYC gene, 50.0, 90.9, 80.0, and 100%; VIA/VILI, 85.7, 81.8, 66.7, and 42.9%. The specificity was: TCT, 98.9, 98.1, 98.8, and 95.2%; HPV test, 96.7, 95.1, 92.2, and 100%; the TERC gene, 95.0, 98.9, 94.0, and 95.2%; the C-MYC gene, 97.2, 97.3, 93.4, and 97.6%; VIA/VILI, 91.2, 90.5, 89.8, and 88.1%, respectively. In the joint model for the diagnosis using different combinations, we found Logit (P) = 5.757 - 4.055 × TCT - 3.724 × HPV. The sensitivity and specificity in the combination program with TCT (primary screening) and HPV testing (adjunct screening) were 78.7 and 99.5%, while in the combination with HPV (primary) and TCT (adjunct), they were 53.2 and 99.7%, respectively. However, in the cytology-HPV parallel test, they were 97.9 and 93.4%. The ROC analysis revealed that the cytology-HPV parallel test is superior to the combinations of either TCT (primary) and HPV (adjunct) or HPV (primary) and TCT (adjunct; AUCTCT-HPV parallel test = 0.956; AUCTCT/primaryHPV/adjunct = 0.764).Conclusions: Opportunistic cervical cancer screening is a practical approach to improve the efficiency of cervical cancer screening. Although the accuracy of TCT is the highest of the five screening methods for the diagnosis of high-grade CIN, it is still subject to sample acquisition and the practitioner's skill and experience. Since the efficacy of VIA/VILI may vary in all ages, it is not recommended for menopausal and perimenopausal women. [ABSTRACT FROM AUTHOR]

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients., Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2)., Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP., Conclusion: Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT03635489., Competing Interests: W.X., L.J., A.R., Y.R., Z.Y., Z.H., H.A., W.L., Z.J., L.Z., D.W., Z.J., L.G., C.G., C.Y., and X.F. received institute research funding from F. Hoffmann-La Roche Ltd. N.S., W.H., and L.D. are employees of F. Hoffmann-La Roche Ltd. N.S. and W.H. own shares in F. Hoffmann-La Roche Ltd., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: Patients with endometrial cancer (EC) combined with metabolic syndrome (MetS) have a worse prognosis than those without MetS. This study aimed to investigate whether partial metabolic disorder significantly influenced early-stage endometrioid EC (EEC) survival and searched for a more efficient method to evaluate metabolic status., Methods: This is a nationwide, multicenter cohort study that included 998 patients with primary early-stage EEC from 2001 to 2018. Patients were divided into different metabolic groups based on the diagnostic criteria of the Chinese Medical Association (CDC). The progression-free survival (PFS) time was compared between various metabolic status. Meanwhile, we established an EC Prognostic-Related Metabolic Score (ECPRM Score) to explore the association of the severity of metabolic status and early-stage EEC PFS. A nomogram was established for predicting PFS, which was externally validated in a testing set that includes 296 patients., Results: A partial metabolic disorder, as well as MetS, was an independent risk factor of poor survival of patients with early-stage EEC [hazard ratio (HR) = 7.6, 95% CI = 1.01-57.5, p < 0.05]. A high ECPRM Score was associated with lower PFS (HR = 2.1, 95% CI = 1.05-4.0, p < 0.001). The nomogram, in which the ECPRM Score contributed most to the prognosis, exhibited excellent discrimination of survival supported by the internal and external validations. In addition, the calibration curve supports its robust predicting ability., Conclusion: Even though they do not meet the criteria of MetS, partial metabolic disorders were also associated with adverse outcomes in early-stage EEC. The ECPRM Score is beneficial for clinicians to evaluate the severity of metabolic abnormalities and guide patients to ameliorate the poor prognosis of metabolic disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Song, Liu, Zhang, Zhang, Wang, Fu, Wang, Yao, Xu, Xia, Lou, Liu, Lin, Wang, Zhao, Zhang, Cheng, Guo, Guo, Xue, Wang, Han, Zhao, Li, Zhang, Zhao, Ma, Yao, Li, Yang, Fang, Chen, Li, Shen, Sun and Kong.)

Objective: The aim of the present study was to determine overall survival (OS) and risk factors associated with early recurrence in patients with FIGO I-II stage endometrial carcinoma (EC)., Methods: Clinical features were retrospectively extracted from the database of China Endometrial Cancer Consortium from January 2000 to December 2019. A total of 2,974 patients with Federation International of Gynecology and Obstetrics (FIGO) I-II stage endometrial cancer were included. Kaplan-Meier survival analysis was used to assess OS and disease-specific survival. Cox proportional hazard model and Fine-Gray model were used to determine the factors related to OS. Binary logistic regression model was used to determine independent predictors of early relapse patients., Results: Of these 2,974 ECs, 189 patients were confirmed to have relapse. The 5-year OS was significantly different between the recurrence and non-recurrence patients ( p < 0.001). Three quarters of the relapse patients were reported in 36 months. The 5-year OS for early recurrence patients was shorter than late recurrence [relapse beyond 36 months, p < 0.001]. The grade 3 [odds ratio (OR) = 1.55, 95%CI 1.17-2.05, p = 0.002], lymphatic vascular infiltration (LVSI; OR = 3.36; 95%CI 1.50-7.54, p = 0.003), and myometrial infiltration (OR = 2.07, 95%CI 1.17-3.65, p = 0.012) were independent risk factors of early relapse. The protective factor of that is progesterone receptor (PR)-positive (OR = 0.50, 95%CI 0.27-0.92, p = 0.02). Bilateral ovariectomy could reduce recurrence risk rate (OR = 0.26, 95%CI 0.14-0.51, p < 0.001)., Conclusion: The OS of early relapse EC is worse. Grade 3, LVSI, and myometrial infiltration are independent risk factors for early relapse EC. In addition, the protective factor is PR-positive for those people and bilateral salpingo-oophorectomy could reduce the risk of recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dou, Song, Fu, Shen, Zhang, Yao, Xu, Xia, Lou, Liu, Lin, Wang, Zhao, Zhang, Cheng, Guo, Guo, Xue, Wang, Han, Zhao, Li, Zhang, Zhao, Ma, Li, Yang, Wang, Liu, Fang, Li, Chen, Sun, Cheng, Jiang, Wang, Luo, Kong and the Chinese Endometrial Carcinoma Consortium (CECC).)

Objective: To systematically evaluate lymph node metastasis (LNM) patterns in patients with endometrial cancer (EC) who underwent complete surgical staging, which included systematic pelvic and para-aortic lymphadenectomy. Methods: Four thousand and one patients who underwent complete surgical staging including systematic pelvic and para-aortic lymphadenectomy for EC were enrolled from 30 centers in China from 2001 to 2019. We systematically displayed the clinical and prognostic characteristics of patients with various LNM patterns, especially the PLN-PAN+ [para-aortic lymph node (PAN) metastasis without pelvic lymph node (PLN) metastasis]. The efficacy of PAN+ (para-aortic lymph node metastasis) prediction with clinical and pathological features was evaluated. Results: Overall, 431 of the 4,001 patients (10.8%) showed definite LNM according to pathological diagnosis. The PAN+ showed the highest frequency (6.6%) among all metastatic sites. One hundred fourteen cases (26.5%) were PLN-PAN+ (PAN metastasis without PLN metastasis), 167 cases (38.7%) showed PLN+PAN-(PLN metastasis without PAN metastasis), and 150 cases (34.8%) showed metastasis to both regions (PLN+PAN+). There was also 1.9% (51/2,660) of low-risk patients who had PLN-PAN+. There are no statistical differences in relapse-free survival (RFS) and disease-specific survival (DSS) among PLN+PAN-, PLN-PAN+, and PLN+PAN+. The sensitivity of gross PLNs, gross PANs, and lymphovascular space involvement (LVSI) to predict PAN+ was 53.8 [95% confidence interval (CI): 47.6-59.9], 74.2 95% CI: 65.6-81.4), and 45.8% (95% CI: 38.7-53.2), respectively. Conclusion: Over one-fourth of EC patients with LMN metastases were PLN-PAN+. PLN-PAN+ shares approximate survival outcomes (RFS and DSS) with other LNM patterns. No effective clinical methods were achieved for predicting PAN+. Thus, PLN-PAN+ is a non-negligible LNM pattern that cannot be underestimated in EC, even in low-risk patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Jiang, Fu, Shen, Zhang, Yao, Xu, Xia, Lou, Liu, Lin, Wang, Zhao, Zhang, Cheng, Guo, Guo, Xue, Wang, Han, Zhao, Li, Zhang, Zhao, Ma, Yao, Yang, Dou, Wang, Liu, Fang, Li, Wang, Chen, Cheng, Sun and Kong.)

Endometrial carcinogenesis may be related to the long-term effects of estradiol with no antagonism. However, how estradiol regulates cell proliferation is unknown. In the present study, through investigating the molecular events involved in estradiol induced angiogenics factors VEGF and bFGF, we found that estradiol induced endometrial cancer cell division, proliferation, migratory and invasive capacity in vitro and upregulated mRNA expression and protein synthesis of VEGF and bFGF. The estradiol-dependent induction of the expression of VEGF and bFGF was blocked by ER inhibitor, AKT inhibitor and NF-κB inhibitor (PDTC) in estrogen receptor positive Ishikawa cells and blocked by AKT inhibitor, NF-κB inhibitor (PDTC) in estrogen receptor negative HEC-1A cells. Moreover, estradiol activation of AKT was also blocked by AKT antagonist. NF-κB activation was restricted by estradiol concentration and time. Estradiol leading to VEGF and bFGF induction was also confirmed by the development of xenograft tumors in vivo. Taken together, our data suggest that estradiol induces the production of angiogenic factors via a mechanism involving AKT-mediated NF-κB activation partly in non-genomic manner without the estrogen receptor.

Objective: To evaluate the short- term and long- term outcomes after laparoscopic surgery compared with traditional laparotomy in patients with stage I-II endometrial cancer., Methods: A retrospective study of population among 673 patientsfor early-stage endometrial cancer between Jan. 2007 and May 2014 was involved from 6 third-grade class-A communal hospitals in Guangxi. Three hundred and seventy-six cases were performed by laparoscopy, 297 cases by laparotomy. The t-test and χ(2) test was used to compare the short-term and long-term outcomes. The short-term outcomes including surgical related outcomes and operative complications, the long- term outcomes including quality of life (pelvic floor functions and sexual functions), survival analysis and recurrence. The International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Sympotom (ICIQ- FLUTS) and the Female Sexual Function Index (FSFI) were used to assess pelvic floor function and sexual function. Survival rates were estimated by Kaplan-Meier analysis. The survival curves were compared by log-rank test. Cox regression analysis was used to select the risk factors for prognosis., Results: (1) The short-term outcomes: There were significant difference in operative time [(258±71) vs (226±69) minutes], estimated blood loss [(343± 211) vs (491±411) ml], anus exhausting time [(2.3±0.9) vs (2.9±1.0) days], preserved days of installing catheter [(7 ± 5) vs (10±8) days], post- operative length of stay [(12 ± 7) vs (18 ± 12) days] between laparoscopic group andlaparotomy group (all P <0.05). While, there was no significant difference in lymph nodes yielded (21±8 vs 21±11; P>0.05),the intra-operative complications occurred [8.5%(32/376) vs 10.4%(31/297); P>0.05], and the post-operative complications [18.1% (68/376) vs 22.2% (66/297); P>0.05] between laparoscopic group and laparotomy group. However, the complications of vascular injury and the poor wound healing in laparoscopic group were respectively lower than those in laparotomy group [1.9%(7/376) vs 5.4% (16/297), P=0.003; and 0.3% (1/376) vs 4.7% (14/297), P<0.01]. (2) The long- term outcomes: There were no significant differences in overall survival (OS) and the degree of incontinence in ICIQ-FLUTS questionnaire between the two groups (all P >0.05). The sexual desire and sexual satisfaction scores dimension after 12 months of post- operative in FSFI questionnaire in the laparoscopic group were higher than those in laparotomy group (all P <0.05). However, there were no significant differences in sexual arousal, vaginal lubrication, orgasm and sexual pain dimension scores between the two groups (all P >0.05). The recurrence rate was 12.0%(45/376) in laparoscopic group and 14.5%(43/297) in laparotomy group (P= 0.269). The 5-year OS was 89.5% in the laparoscopic group and 87.2% in the open group (P >0.05) , and the 5-year free-progression survival rate was 87.9% in the laparoscopic group and 85.1% in the open group (P >0.05). (3) Prognostic factors in laparoscopic group: The univariate analysis shown that pathological type, surgical pathological staging, deep myometrial invasion, and retroperitoneal lymph node-positive were significantly affected prognosis in laparoscopic group (all P<0.01). The multivariate analyses showed that pathological type and surgical pathological stage were the independent prognostic factors (all P<0.01)., Conclusions: Laparoscopy could reduce estimated blood loss, accelerate postoperative recovery and improve the quality of life after surgery compared to laparotomy, also ensure the same oncologically results as that by laparotomy. So, laparoscopic approach is a safe and effective treatment method for early- stage endometrial cancer.

Objective: To discuss the risk factors and prognosis of gynecologic cancer patients with deep venous thrombosis (DVT)., Methods: Data from gynecologic cancer patients diagnosed by cytology or histopathology in Affiliated Tumor Hospital of Guangxi Medical University between Jan. 1994 and Sep. 2014 were collected, including 106 cases in the DVT group, according to 1:1 proportion by the computer random method to selecting patients without DVT as the control group. The follow-up deadline was March 31, 2015. The median follow-up time of DVT group was 27.0 months (range, 1 to 169 months), while the control group was 33.5 months (range, 1 to 125 months). Univariate analysis was performed by two independent sample t test or χ² test. Multivariate analysis was performed by logistic regression analysis. The Kaplan-Meier curve was used to estimate the survival analysis., Results: (1) The univariate analysis showed that body mass index (BMI), hypertension, diabetes, history of thrombosis, tumor stage, blood transfusion, stimulating factor, white blood cell (WBC), platelet (PLT), prothrombin time (PT) and fibrinogen (FIB) were statistically significant associated with DVT (P < 0.05). Multivariate analysis showed that tumor stage, stimulating factor, WBC, PT and FIB may be the independent risk factors of gynecologic cancer with DVT (P < 0.05). (2) The median survival time in DVT group was 66 months, while the control group was 102 months (χ² = 7.039, P = 0.008). The overall survival and progression-free survival in the DVT group were statistically significant lower than those in the control group (P < 0.05). The tumor stage, the scope of DVT (whether with pulmonary embolism) and the treatment of DVT were the effective factors influenced the prognosis of gynecologic oncology patients with DVT (P < 0.05). Cox regression model showed that tumor stage and the scope of DVT were the independent risk factors (P < 0.01)., Conclusions: Gynecologic cancer with DVT is the common effect of various risk factors. We should identify the risk factors for high-risk patients and take preventive measures actively to reduce the deep venous thromboembolism, then improve the survival of patients and their prognosis.

To evaluate the feasibility and surgical outcome of video endoscopic inguinal lymphadenectomy (VEIL) using a hypogastric subcutaneous approach, 21 patients with vulvar cancer who underwent this procedure were included in the present study. Between December 2010 and March 2013, 21 consecutive patients with vulvar cancer underwent radical vulvectomy and VEIL using a hypogastric subcutaneous approach. The intraoperative and post-operative results and follow-up data were retrospectively analyzed. No intraoperative complications occurred. The mean duration of surgery for the endoscopic inguinal lymphadenectomies was 130 min (range, 80-180 min), with a mean estimated blood loss of 103 ml (range, 30-350 ml). The mean lymph node yield was 15 (range, 10-22 lymph nodes). The suction drains were removed after a mean duration of 7 days (range, 5-11 days). No skin-related complications were observed in the groin region and a lymphocele was only observed in 1/21 (4.8%) patients. After a mean follow-up period of 17 months (range, 3-31 months), recurrence was found in only one patient. All the patients were alive at the time of publication. Based on our preliminary experience, performing VEIL using a hypogastric subcutaneous approach is a safe and feasible technique for patients with vulvar cancer. These results indicate that this surgical technique may decrease the post-operative morbidity of lymphadenectomy without compromising the therapeutic efficacy. Future prospective studies with a greater sample size and a longer duration of follow-up are required.

Objective: To explore the effects of mitogen-activated protein kinase (MAPK) pathway by estradiol induced vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in endometrial cancer Ishikawa cells., Methods: The experiments were divided into 4 groups: E2 group (Ishikawa cells treated with 1 µmol/L estradiol for 30 minutes); inhibitor group: including Ishikawa cells treated with 10 µmol/L Bibf1120 (Bibf1120 group), or treated with 2.5 µmol/L Ponatinib (Ponatinib group), or treated with 10 µmol/L U0126 (U0126 group) for 60 minutes; inhibitor + E2 group: including Ishikawa cells treated with 10 µmol/L Bibf1120 (Bibf1120 + E2 group), or treated with 2.5 µmol/L Ponatinib (Ponatinib + E2 group), or treated with 10 µmol/L U0126 (U0126 + E2 group) for 60 minutes following incubation with 1 µmol/L estradiol for 30 minutes;control group: only adding the culture medium without serum DMEM. (1) Western blot analysis was used to detect phosphorylation extracellular signal-regulated kinase 1/2(p-ERK1/2) protein expression with stimulation in different concentrations of estradiol (0.01,0.1, 1, 10, 100 µmol/L). (2)Quantitative fluorescent reverse transcription (qRT)-PCR and western blot analysis was used to test the level of mRNA and protein of VEGF, bFGF, MAPK kinase 1/2 (MEK1/2), extracellular signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2 and phosphorylation MEK1/2(p-MEK1/2). Flow cytometry were used to examine the cell cycle, and transwell chamber assay were used to detect the cell migration in different groups., Results: The expression of the p-ERK1/2 protein at 0.01,0.1, 1, 10, 100 µmol/L were 0.16±0.03, 0.10±0.03, 0.41±0.04, 0.19±0.03, 0.19±0.03, there were significantly higher than that in control group (0.05±0.00, P < 0.05), and which was more obvious at the concentration of 1 µmol/L estradiol. The expression level of VEGF, bFGF mRNA and protein in E2 group were higher than those in the control group(P < 0.05). VEGF mRNA and protein in Bibf1120+E2 group were higher than those in E2 group. The expression of MEK1/2, ERK1/2 mRNA protein in E2 group were higher than those in control group (P < 0.05). The expression of MEK1/2, ERK1/2 mRNA or p-MEK1/2, p-ERK1/2 protein in Bibf1120 + E2 group, Ponatinib+E2 group or U0126+E2 group were lower than those in E2 group (all P < 0.05). Percentage of G1 phase ([53.6±3.2)%] and S phase ([ 29.2±4.2)%] in E2 group was significantly different with those in control group respectively(P < 0.05). Percentage of G1 phase [(66.8±2.6)%, (63.1±2.6)% and (63.3±0.4)%] and S phase [(25.4±1.9)%, (25.0±3.8)% and (23.8±0.5)%] in U0126+E2 group, Bibf1120+E2 group or Ponatinib +E2 group was also significantly different with those in control group(all P < 0.05); percentage of G1 phase and S phase in U0126+E2 group was significant difference with those in Bibf1120+E2 group or ponatinib+E2 group (P < 0.05). The number of cell colony in E2 group (110±17) was more than those in control group(65±8);the number of cell colony in U0126+E2 group (28±4), Bibf1120+E2 group (38±5) or Ponatinib+E2 group (42±6) were significant different with those in E2 group (P < 0.05), the number of cell colony in U0126+E2 group was significant difference with those in Bibf1120+E2 group or Ponatinib+E2 group (all P < 0.05). The results shown that the abilities of proliferation and cell migration were significantly increased in cells after estradiol stimulation., Conclusion: Estradiol inducing the production of VEGF and bFGF could activate MAPK pathway through ER-independent manner, further promote development.

Objective: The aim of this study was to explore whether estradiol induces the expression of VEGF and bFGF in the endometrial cancer Ishikawa cells by activation of NF-κB via AKT pathway, and its effect on cell proliferation., Methods: Western blot was used to detect the AKT protein expression in Ishikawa cells after stimulation with estradiol, and the effect of AKT inhibitor or ER inhibitor on the activation of AKT. TransAM kit was used to detect the NF-κB p65 activity. qPCR and Western blot were used to detect the expression of VEGF and bFGF mRNA and proteins in the Ishikawa cells after estradiol treatment (E2 group), and pretreated with AKT inhibitor (AKT group) or ER inhibitor (ER group) or NF-κB inhibitor (NF-κB group), following the estradiol treatment. Flow cytometry and CFSE (carboxyfluorescein diacetate, succinimidyl ester) staining were used to examine the cell proliferation. Transwell was used to detect the migration ability of Ishikawa cells., Results: Expression of p-AKT protein in the Ishikawa cells was markedly higher than that in the control group (P < 0.05). Expressions of p-AKT protein in the AKT and ER groups were significantly decreased than that in the E2 group (P < 0.05). The NF-κB activity was highest after stimulation with 1×10(-6) mol/L estradiol for 30 min to 1 h. AKT inhibitor significantly reduced the NF-κB activity (P < 0.05). The expressions of VEGF and bFGF mRNA and proteins in the E2 group were significantly increased than that in the control group (P < 0.05), and their expression in the AKT, ER and NF-κB groups were significantly decreased than that in the E2 group (P < 0.05). The proliferation and migration abilities of the Ishikawa cells were significantly increased after estradiol stimulation., Conclusions: Estradiol induces the production of VEGF and bFGF through activating NF-κB via AKT pathway, and enhances the proliferation and migration ability of cancer cells.

It has been reported that heparanase (HPSE) is overexpressed in ovarian cancer and is associated with tumor invasion and metastasis. However, a systematic study on the contribution of HPSE to tumor metastasis is rarely reported. In this study, based on the measurement of HPSE serum concentration, the expression of HPSE at both the mRNA and protein levels in tumors and its effects on the biological behaviors of cancer cells, we elucidated the role of HPSE in tumor invasion and metastasis in ovarian cancer and concluded that either the expression of HPSE in cancer and/or the serum concentration of HPSE may be a useful biomarker for the evaluation of surgery effects and prognosis prediction.

The aim of this study was to evaluate serum human epididymis protein 4 (HE4) concentrations for the diagnosis and preoperative prediction of optimal debulking in epithelial ovarian cancer. The concentrations of serum HE4 and CA125 in 180 epithelial ovarian cancer patients, 40 benign ovarian tumor patients and 40 healthy female subjects were determined using enzyme-linked immunosorbent assays (ELISAs). The value of determining the serum HE4 concentrations for the diagnosis and preoperative prediction of optimal debulking in epithelial ovarian cancer was also analyzed. The concentration of serum HE4 was 355.2±221.29 pmol/l in ovarian cancer, 43.86±20.87 pmol/l in benign ovarian tumors and 30.22±9.64 pmol/l in healthy individuals, respectively. The serum HE4 levels of patients with ovarian cancer were significantly higher compared with those in the other two groups (P<0.01), although there were no statistically significant differences (P>0.05) between the benign ovarian tumors and healthy individuals. The maximum diagnostic value was identified at an HE4 serum concentration of 67.52 pmol/l and the sensitivity and specificity were 84 and 96%, respectively. The area under the ROC curve was 0.944 (95% CI, 0.912-0.976; P<0.001) and the κ value of the diagnosis of epithelial ovarian cancer according to HE4 was 0.814 (P=0.000). The demarcation criterion was 600 pmol/l, where a value >600 mol/l indicates a lower possibility of optimal debulking. HE4 predicted that the sensitivity of the incomplete cytoreductive surgery was 77% and specificity was 32%. The concentration of serum HE4 is a useful marker for diagnosis and preoperative prediction for the ideal tumor cytoreductive surgery in epithelial ovarian cancer.

The urokinase plasminogen activator system, which consists of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and urokinase plasminogen activator receptor (uPAR), plays an important role in tumor invasion and metastasis, and it may be a potential diagnostic biomarker and therapeutic target in cancer. It has been found that the expression of uPA and PAI-1 in ovarian cancer is related to clinical pathologies, while their effects on the biological behavior of tumor cells and their clinical significance are still unknown. In this study, 100 tissue samples (60 samples from malignant tumors, 20 from benign tumors and 20 from controls) and 147 blood samples (49 samples each from patients with malignant tumors, benign tumors and control group, respectively) were analyzed. The positive expression levels of uPA and PAI-1 in the malignant tumor samples and their serum concentrations in the malignant group were all significantly higher than these levels in the benign tumors and controls. In addition, the levels in patients with poorly differentiated and stage III-IV cancers, cancers with metastases as well as residual tumors >2 cm after surgery, were all obviously increased, consistent with their concentrations in serum. The Cox model analysis showed that expression of uPA at the transcription level had significant associations with prognosis. In addition, uPA greatly enhanced the abilities of cell invasion, migration and adhesion through its overexpression in SKOV3 cells. Collectively, our results showed that uPA and PAI-1 play important roles in ovarian cancer development; therefore, their expression in tissues and their concentrations in serum would greatly assist the diagnosis and prediction of the prognosis in ovarian cancer.

The WW domain-containing oxidoreductase (WWOX) gene is located at FRA16D, a common fragile site involved in human cancer. Targeted deletion of Wwox in mice causes increased spontaneous tumor incidence, confirming that WWOX is a bona fide tumor suppressor gene. We show that stable transfection of WWOX into human PEO1 ovarian cancer cells, containing homozygous WWOX deletion, abolishes in vivo tumorigenicity, but this does not correlate with alteration of in vitro growth. Rather, WWOX restoration in PEO1, or WWOX overexpression in SKOV3 ovarian cancer cells, results in reduced attachment and migration on fibronectin, an extracellular matrix component linked to peritoneal metastasis. Conversely, siRNA-mediated knockdown of endogenous WWOX in A2780 ovarian cancer cells increases adhesion to fibronectin. In addition, whereas there is no WWOX-dependent difference in cell death in adherent cells, WWOX-transfected cells in suspension culture display a proapoptotic phenotype. We further show that WWOX expression reduces membranous integrin alpha(3) protein but not integrin alpha(3) mRNA levels, and that adhesion of PEO1 cells to fibronectin is predominantly mediated through integrin alpha(3). We therefore propose that WWOX acts as an ovarian tumor suppressor by modulating the interaction between tumor cells and the extracellular matrix and by inducing apoptosis in detached cells. Consistent with this, the suppression of PEO1 tumorigenicity by WWOX can be partially overcome by implanting these tumor cells in Matrigel. These data suggest a possible role for the loss of WWOX in the peritoneal dissemination of human ovarian cancer cells.

Vascular endothelial growth factor (VEGF) has been shown to play an important role in tumor growth and progression. However, the clinical implications of VEGF expression in ovarian tumors are not fully understood. We therefore investigated the serum level of VEGF in patients with ovarian tumors and explored the potential use of VEGF as a tumor marker for diagnosis, treatment and prognosis of human ovarian cancer. The serum VEGF (sVEGF) levels in 120 patients with ovarian carcinoma, 25 patients with benign ovarian tumor and 90 healthy female blood donors were measured by an enzyme-linked immunosorbent assay in this study. We also determined the levels of sVEGF in patients with epithelial ovarian cancer before and after surgery. Our results showed that: (i) ovarian cancer patients had significantly higher levels of sVEGF compared to those of patients with benign ovarian tumor or those of healthy individuals. As a cut-off at 100 pg/ml, the sensitivity and specificity of sVEGF levels for diagnosing ovarian carcinoma were 77.1% and 87%, respectively. (ii) sVEGF levels were markedly elevated in patients with advanced stage or poorly-differentiated ovarian cancer, as well as in those with more ascites (>500 ml), as compared to patients with early stage and well-differentiated ovarian cancer, or those with less ascites (<500 ml). However, there was no significant difference in sVEGF levels among different pathological subtypes of ovarian carcinoma. (iii) The post-operative sVEGF levels were significantly lower than the pre-operative sVEGF levels. (iv) We measured significantly higher levels of sVEGF in patients with metastasis as compared to patients lacking metastasis. Lastly (v) the average survival-time in patients with higher levels of sVEGF (>100 pg/ml) was 28 months, while the average survival-time in patients with lower levels of sVEGF (<100 pg/ml) was 35 months, indicating that the elevations in sVEGF level are correlated with patient survival and tumor metastasis in ovarian carcinoma. These data suggest that VEGF may be a useful serological biomarker for clinical diagnosis and prognosis of ovarian cancer, for follow-up of ovarian tumor metastasis and for monitoring the efficacy of therapy in patients with ovarian carcinomas.