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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 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.

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.