Characterization and application of in situ curcumin/ZNP hydrogels for periodontitis treatment.

BACKGROUND: Periodontitis is a chronic inflammatory disease that occurs in tooth-supporting tissues. Controlling inflammation and alleviating periodontal tissue destruction are key factors in periodontal therapy. This study aimed to develop an in situ curcumin/zinc oxide (Cur/ZNP) hydrogel and investigate its characteristics and effectiveness in the treatment of periodontitis. METHODS: Antibacterial activity and cytotoxicity assays were performed in vitro. To evaluate the effect of the in situ Cur/ZNP hydrogel on periodontitis in vivo, an experimental periodontitis model was established in Sprague‒Dawley rats via silk ligature and inoculation of the maxillary first molar with Porphyromonas gingivalis. After one month of in situ treatment with the hydrogel, we examined the transcriptional responses of the gingiva to the Cur/ZNP hydrogel treatment and detected the alveolar bone level as well as the expression of osteocalcin (OCN) and osteoprotegerin (OPG) in the periodontal tissues of the rats. RESULTS: Cur/ZNPs had synergistic inhibitory effects on P. gingivalis and good biocompatibility. RNA sequencing of the gingiva showed that immune effector process-related genes were significantly induced by experimental periodontitis. Carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1), which is involved in the negative regulation of bone resorption, was differentially regulated by the Cur/ZNP hydrogel but not by the Cur hydrogel or ZNP hydrogel. The Cur/ZNP hydrogel also had a stronger protective effect on alveolar bone resorption than both the Cur hydrogel and the ZNP hydrogel. CONCLUSION: The Cur/ZNP hydrogel effectively inhibited periodontal pathogenic bacteria and alleviated alveolar bone destruction while exhibiting favorable biocompatibility.

Phospholipase D1 promotes cervical cancer progression by activating the RAS pathway.

This study aimed to further investigate the effect of PLD1 on the biological characteristics of human cervical cancer (CC) cell line, CASKI and the potential related molecular mechanism. CRISPR/Cas9 genome editing technology was used to knock out the PLD1 gene in CASKI cells. Cell function assays were performed to evaluate the effect of PLD1 on the biological function of CASKI cells in vivo and in vitro. A PLD1-overexpression rescue experiment in these knockout cells was performed to further confirm its function. Two PLD1-knockout CASKI cell lines (named PC-11 and PC-40, which carried the ins1/del4 mutation and del1/del2/ins1 mutation, respectively), were constructed by CRISPR/Cas9. PLD1 was overexpressed in these knockout cells (named PC11-PLD1 and PC40-PLD1 cells), which rescued the expression of PLD1 by approximately 71.33% and 74.54%, respectively. In vivo, the cell function assay results revealed that compared with wild-type (WT)-CASKI cells, the ability of PC-11 and PC-40 cells to proliferate, invade and migrate was significantly inhibited. The expression of H-Ras and phosphorylation of Erk1/2 (p-Erk1/2) was decreased in PC-11 and PC-40 cells compared with WT-CASKI cells. PC-11 and PC-40 cells could sensitize CASKI cells to cisplatin. More importantly, the proliferation, migration and invasion of PC11-PLD1 and PC40-PLD1 cells with PLD1 overexpression were significantly improved compared with those of the two types of PLD1 knockout cells. The sensitivity to cisplatin was decreased in PC11-PLD1 and PC40-PLD1 cells compared with PC-11 and PC-40 cells. In vivo, in the PC-11 and PC-40 tumour groups, tumour growth was significantly inhibited and tumour weight (0.95 ± 0.27 g and 0.66 ± 0.43 g vs. 1.59 ± 0.67 g, p = 0.0313 and 0.0108) and volume (1069.41 ± 393.84 and 1077.72 mm3 ± 815.07 vs. 2142.94 ± 577.37 mm3 , p = 0.0153 and 0.0128) were significantly reduced compared to those in the WT-CASKI group. Tumour differentiation of the PC-11 and PC40 cells was significantly better than that of the WT-CASKI cells. The immunohistochemistry results confirmed that the expression of H-Ras and p-Erk1/2 was decreased in PC-11 and PC-40 tumour tissues compared with WT-CASKI tumour tissues. PLD1 promotes CC progression by activating the RAS pathway. Inhibition of PLD1 may serve as an attractive therapeutic modality for CC.

Soy isoflavones alleviate periodontal destruction in ovariectomized rats.

OBJECTIVE: The purpose of this study was to investigate whether soy isoflavone supplementation is effective in preventing periodontal destruction exacerbated by estrogen deficiency (ED) and its potential mechanism. BACKGROUND: The progression of periodontitis is affected by host factors, such as smoking, diabetes mellitus, and steroid use. Bone loss in periodontitis can be aggravated by ED. METHODS: A rat model of experimental periodontitis (EP) with ED was established by silk ligature and inoculation with Porphyromonas gingivalis, and some EP rats were subjected to bilateral ovariectomy (OVX). The treatment groups received an intravenous injection of 17-ß-estradiol (E2 B) or soy isoflavones (SI) by gavage. The rats were euthanized, and the maxillary jaws, gingiva, and serum were harvested. Tight junction protein and interleukin (IL)-17 expression, reactive oxygen species (ROS) level, and periodontal destruction were assessed. In addition, we determined whether grainyhead-like 2 (GRHL2) is required for enhancing the epithelial barrier by SI in an in vitro P. gingivalis infection model. RESULTS: Estrogen deficiency impaired the expression of genes encoding tight junction proteins in the gingiva, increased IL-17 level, and accelerated alveolar bone resorption. SI treatment alleviated tight junction protein expression, decreased IL-17 and ROS levels, and prevented the absorption of alveolar bone. Furthermore, GRHL2 expression was significantly induced by SI in human oral keratinocytes-1 (HOK-1) cells; GRHL2 knockdown impaired the expression of OCLN and ZO-1 induced by SI treatment. CONCLUSION: Soy isoflavones alleviates periodontitis in OVX rats, as observed by the increased expression of tight junction proteins, and reduced IL-17 level and alveolar bone loss. The in vitro studies suggested that the enhancement of oral epithelial barrier by SI treatment was partially dependent on GRHL2.

DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway.

To determine the differentially expressed proteins (DEPs) between paired samples of cervical cancer (CC) and paracancerous tissue by quantitative proteomics and to examine the effects of DUSP7 expression on the tumorigenesis and progression of CC. Proteomic profiles of three paired samples of CC and paracancerous tissue were quantitatively analysed to identify DEPs. The relationship between DEP expression and patient clinicopathological characteristics and prognosis was evaluated. The effects of the selected DEPs on CC progression were examined in SIHA cells. A total of 129 DEPs were found. Western blot and immunohistochemistry (IHC) staining analyses confirmed the results from quantitative proteomic analysis showing that the selected DEP, HRAS, P-ERK1/2, and PLD1 levels were increased, whereas the DUSP7 level was decreased in CC tissue compared with the paired normal paracancerous tissues. The IHC results from the CC TMA analysis showed that the decreased expression of DUSP7 (p = 0.045 and 0.044) was significantly associated with a tumour size >2 cm and parametrial infiltration. In addition, the decreased expression of DUSP7 and increased expression of p-ERK1/2 were adversely related to patient relapse (p = 0.003 and 0.001) and survival (p = 0.034 and 0.006). The expression of HRAS and p-ERK1/2 was decreased in DUSP7-SIHA cells compared with NC-SIHA cells (p = 0.0003 and 0.0026). Biological functions in vitro, including invasion, migration and proliferation and tumour formation in vivo were decreased in DUSP7-SIHA cells (all p < 0.05) but increased in shDUSP7-SIHA cells (all p < 0.05). DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway.

The Role of Lysophosphatidic Acid Receptors in Ovarian Cancer: A Minireview.

Lysophosphatidic acid (LPA) is a bioactive lipid component of ovarian cancer activating factor, which is present at a high concentration in the ascitic fluid and plasma of patients with ovarian cancer. A group of six lysophosphatidic acid receptors (LPARs), LPAR1 through LPAR6, which belong to the G protein-coupled receptor superfamily (GPCR), mediate cellular activities of LPA and activates a series of downstream molecules and cellular responses, including biological and pathological effects. LPARs are widely expressed in normal ovary, benign tumor, and ovarian cancer tissues and cancer cell lines with a broad range of levels. The LPA/LPAR axis is involved in tumorigenesis and development of ovarian cancer through mediating the cellular responses to LPA and influencing the expression and function of oncogenic molecules. In the present review, the roles of LPARs in ovarian cancer, including the expression, function, and downstream molecules, are summarized, and we discuss the implications for ovarian cancer treatment that targets LPARs.

PARP inhibitors in ovarian cancer: Sensitivity prediction and resistance mechanisms.

Poly (ADP-ribose) polymerase (PARP) inhibitors have provided great clinical benefits to ovarian cancer patients. To date, three PARP inhibitors, namely, olaparib, rucaparib and niraparib have been approved for the treatment of ovarian cancer in the United States. Homologous recombination deficiency (HRD) and platinum sensitivity are prospective biomarkers for predicting the response to PARP inhibitors in ovarian cancers. Preclinical data have focused on identifying the gene aberrations that might generate HRD and induce sensitivity to PARP inhibitors in vitro in cancer cell lines or in vivo in patient-derived xenografts. Clinical trials have focused on genomic scar analysis to identify biomarkers for predicting the response to PARP inhibitors. Additionally, researchers have aimed to investigate mechanisms of resistance to PARP inhibitors and strategies to overcome this resistance. Combining PARP inhibitors with HR pathway inhibitors to extend the utility of PARP inhibitors to BRCA-proficient tumours is increasingly foreseeable. Identifying the population of patients with the greatest potential benefit from PARP inhibitor therapy and the circumstances under which patients are no longer suited for PARP inhibitor therapy are important. Further studies are required in order to propose better strategies for overcoming resistance to PARP inhibitor therapy in ovarian cancers.

LPAR1 regulates the development of intratumoral heterogeneity in ovarian serous cystadenocarcinoma by activating the PI3K/AKT signaling pathway.

BACKGROUND: To explore the role of lysophosphatidic acid receptor 1 (LPAR1) and its correlation with the PI3K/AKT pathway in the development of intratumoral heterogeneity (ITH) in human ovarian serous cystadenocarcinoma (OSC). METHODS: Immunohistochemical staining was performed to detect LPAR1 expression in matched primary and recurrent lesions from the same patients. Cell models of ITH were established using the limiting dilution methodology and Transwell invasion/migration assays. LPAR1 expression in the ITH cell models was silenced or upregulated with lentiviral particles, and the biological characteristics were evaluated using various in vitro and in vivo assessments of cell function. The levels of phosphorylated PI3K/AKT (p-PI3K/p-AKT) in LPAR1 knockdown and LPAR1-overexpressing cells were detected. RESULTS: The H-scores for LPAR1 staining in the lymphatic metastatic and recurrent lesions were noticeably higher than in the primary tumor lesions from the same patients (P = 0.024/0.031). High LPAR1 expression was associated with worse progression-free survival and overall survival (P = 0.017/0.039). Biological functions in vitro, including invasion, migration, and proliferation, and tumor formation in vivo were decreased in the LPAR1-silenced cells (all P < 0.05). These cellular functions were significantly increased in the LPAR1-overexpressing cells in vitro and in vivo (all P < 0.05). The levels of p-PI3K and p-AKT were significantly decreased in the LPAR1 knockdown cells and significantly increased in the LPAR1-overexpressing cells (all P < 0.05). CONCLUSIONS: Higher levels of the LPAR1 protein were associated with a poor prognosis. LPAR1 plays essential roles in the invasion, migration, and proliferation of heterogeneous subsets of OSC cell lines and the development of ITH of OSC, possibly by modulating the activity of the PI3K/AKT signaling pathway.

The clinical benefits of hormonal treatment for LG-ESS: a meta-analysis.

PURPOSE: To evaluate the clinical benefits of hormonal treatment for patients with low-grade endometrial stromal sarcoma (LG-ESS) by reviewing the published literature and performing a meta-analysis. METHODS: Correlational studies related to hormonal treatment for LG-ESS patients were collected by searching the PubMed, EMBASE, and Cochrane databases up to December 2018. Eligible studies were selected based on inclusion and exclusion criteria. The main inclusion criteria included: original studies with definite diagnoses of LG-ESS that evaluated the clinical benefits of hormonal treatment, studies with at least 10 cases, and studies published in English. Reviews, case reports, letters, comments or conference abstracts, studies without sufficient data and overlapping or republished studies were excluded. The study quality was evaluated, and pooled relative risks and 95% confidence intervals were calculated using Review Manager 5.3. RESULTS: A total of 10 retrospective studies were included. The NOS stars of the 10 studies ranged from 7 to 9 points, which was considered to be of high quality. Recurrence and death information was provided in 9 and 6 studies, respectively. The overall pooled RR for recurrence was 0.66 (95% CI 0.47-0.94), which indicated that hormonal treatment was effective at reducing the recurrence risk (P = 0.02). The overall pooled RR for death was 0.81 (95% CI 0.59-1.12), which showed that hormonal treatment had little effect in prolonging overall survival (P = 0.20). Stratified analysis showed that compared with the group without any adjuvant treatments, hormonal treatment alone significantly decreased the risk of recurrence (P = 0.02), while hormonal treatment had no significant effects on overall survival (P = 0.38). Another subgroup analysis indicated that for stage I-II patients, hormonal treatment could significantly decrease the risk of recurrence (P = 0.02) but could not influence overall survival (P = 0.87). However, for stage III-IV patients, hormonal treatment had little benefit both in reducing the recurrence risk and prolonging overall survival (P = 0.49/0.08). Egger's and Begg's test showed that the publication bias for the literature was satisfactorily controlled. CONCLUSION: Adjuvant hormonal treatment should be considered as a feasible adjuvant therapy for reducing the recurrence risk of patients with LG-ESS while bearing little benefit on overall survival.

The security of radical trachelectomy in the treatment of IA-IIA cervical carcinoma requires further evaluation: updated meta-analysis and trial sequential analysis.

PURPOSE: The aim of this study was to assess the security of radical trachelectomy (RT) in the treatment of IA-IIA cervical carcinoma and conducted a new survey based upon the results of previous researches. METHODS: The PMC, PubMed, Web of Science, Cochrane and EMBASE databases were retrieved to collect prospective clinical controlled trials (CCTs) published from 1984 to 2018. The oncologic outcomes were evaluated by meta-analysis, trial sequence analysis (TSA) and statistical analysis. RESULTS: Five prospective CCTs were collected in this study. The recurrence rate and mortality of RT was similar to that of radical hysterectomy (RH), which was consistent with the oncologic outcomes of meta-analysis and TSA. Patients with tumors 2-4 cm in diameter were more likely to receive RH, which may be a potential factor in the higher rate of adjuvant chemotherapy in the this group, and RH was significantly associated with the risk of intraoperative blood transfusion. It is notable that considerable negative margin was achieved by radical abdominal trachelectomy (RAT), and the clinical effect of RAT was slightly better than that of radical vaginal trachelectomy (RVT). However, the TSA results showed that the cumulative cases were not up to the required sample size to obtain the true negative or positive results. CONCLUSIONS: It is safe and effective for early-stage patients with cervical cancer whose lesions are less than 2 cm to receive RVT. For those patients with lesions 2-4 cm who desire fertility preservation and without any evidence of infertility, RAT can be a feasible alternative to RH under fully informed consent. However, more CCTs with larger sample size are still required for further validation.

Oncological and reproductive outcomes of adenocarcinoma in situ of the cervix managed with the loop electrosurgical excision procedure.

BACKGROUND: The standard treatment for cervical adenocarcinoma in situ (AIS) is hysterectomy, which is a more aggressive treatment than that used for squamous intraepithelial lesions. Several previous studies have primarily demonstrated that the loop electrosurgical excision procedure (LEEP) is as safe and effective as cold knife cone (CKC) biopsy when AIS is unexpectedly found in a loop excision. This study evaluated the safety of LEEP as the initial treatment for patients with AIS who were strictly selected and evaluated before and after loop resection. METHODS: The oncological and reproductive outcomes of a series of AIS patients who underwent LEEP as the initial treatment between February 2006 and December 2016 were retrospectively evaluated. RESULTS: A total of 44 women were eligible for analysis. The mean age at diagnosis was 36.1 years, and 14 patients were nulliparous. Multiple lesions were identified in 4 (9.1%) patients. Either hysterectomy (6 patients) or repeat cone biopsies (3 patients) were performed in 8 of the 10 patients who presented positive or not evaluable surgical resection margins (SMs) on the initial LEEP specimens. Residual disease was detected in two patients. All patients were closely followed for a mean of 36.9 months via human papillomavirus testing, PAP smears, colposcopy, and endocervical curettage when necessary. No recurrences were detected. Of the 16 patients who desired to become pregnant, 8 (50%) successfully conceived, and the full-term live birth rate was 83.3% among this subgroup. CONCLUSIONS: LEEP with negative SMs was a safe and feasible fertility-sparing surgical procedure for patients with AIS, and the obstetric outcome was satisfactory. However, long-term follow-up is mandatory.

Management strategies for patients with placenta accreta spectrum disorders who underwent pregnancy termination in the second trimester: a retrospective study.

BACKGROUND: The unique clinical features of pregnancy termination in the second trimester with concurrent placenta accreta spectrum (PAS) disorders place obstetricians in a complex and delicate situation. However, there are limited data on this rare and dangerous condition. The objective of this research was to investigate and evaluate the clinical management strategies of this patient group. METHODS: The medical records of patients who were diagnosed and treated in our hospital from December 2005 and December 2015 were retrospectively reviewed. RESULTS: A total of 29 patients were included in this analysis. A prenatal diagnosis was suspected in 8 (27.6%) patients, and the remaining 21 (72.4%) patients were diagnosed after pregnancy termination in the second trimester. In the subgroup with a prenatal diagnosis, a planned hysterotomy was performed in 7 patients who had total placenta previa and previous cesarean delivery. The remaining patient received medical termination. A subtotal hysterectomy was performed in 3 (10.3%) patients for life-threatening bleeding during hysterotomy, and the uterus was preserved with an in situ placenta in the remaining 5 patients. In the subgroup with a postnatal diagnosis, the implanted placenta remained partly or completely in situ in all 21 patients under informed consent. Ultimately, the implanted placenta remained partly or completely in situ in 26 (89.7%) patients in the two subgroups. With the application of adjuvant treatments, including uterine artery embolization and medication followed by curettage under ultrasound guidance, the implanted placenta was passed 76.6 (range: 19 to 192) days after termination. Uterus preservation was achieved in all 26 patients. The complications associated with conservative management included delayed postnatal hemorrhaging (2 cases, 7.7%), fever (6 cases, 23.1%), G1 transaminase disorder (4 cases, 15.4%), and myelosuppression (1 case, 3.8%). Seven women (26.9%) had a spontaneous pregnancy after conservative management, and no patient experienced recurrent PAS disorders. CONCLUSIONS: Leaving the implanted placenta in situ is the preferred choice for patients with PAS disorders who underwent pregnancy termination in the second trimester and desired fertility preservation. Multiple adjuvant treatment modalities, either alone or in combination, may help to promote the passing or absorption of the implanted placenta under close monitoring.

The safety of fertility preservation for microinvasive cervical adenocarcinoma: a meta-analysis and trial sequential analysis.

PURPOSE: This study sought to evaluate the safety of conservative treatment in the management of patients with microinvasive cervical adenocarcinoma. METHODS: The PubMed, PMC, EMBASE, Web of Science and Cochrane databases were searched to collect correlational studies published in English between January 1949 and May 2018. Series reports that evaluating the oncological prognoses of patients with microinvasive cervical adenocarcinoma who were treated with fertility-sparing surgery versus hysterectomy were pooled for meta-analysis and trial sequential analysis. RESULTS: A total of 8 articles with 1256 patients were collected, including 7 retrospective reviews and 1 prospective study. Only one (0.08%) patient had parametrial involvement. Positive margins of surgical specimens were identified in 6 patients (2.2%). Lymph node metastasis was found in 5 patients (0.4%). The progression-free survival and overall survival rates were 99.3 and 98.2%. Fertility-sparing surgery had no adverse impact on recurrence or survival (P = 0.524 and 0.485, respectively). Regarding potential selection bias, significantly more patients with stage IA2 tumors than those with stage IA1 disease were treated with hysterectomy (P < 0.001). The trial sequential analysis indicated that the cumulative number of patients failed to meet the required sample size (number of patients). CONCLUSIONS: The prognosis for patients with microinvasive cervical adenocarcinoma is excellent. Fertility preservation is at least appropriate for young women with stage IA1 adenocarcinoma. Further studies are still warranted to evaluate the safety of this procedure in managing patients with microinvasive cervical adenocarcinoma.

Sexual Function and Quality of Life Among Patients With Endometrial Cancer After Surgery.

OBJECTIVE: The aim of this study was to evaluate the sexual function and quality of life (QOL) and identify their associated factors in survivors of endometrial cancer. METHODS: The participants in this study were survivors of endometrial cancer who visited the gynecological outpatient department for routine surveillance from June 2014 to May 2015. The QOL and sexual function were measured using the Functional Assessment of Cancer Therapy-General (FACT-G) and Female Sexual Function Index questionnaires. A score less than 26.55 was defined as female sexual dysfunction (FSD). Multivariate analysis and logistic regression were performed to identify the factors associated with QOL and sexual function. RESULTS: A total of 118 women completed the questionnaires. The results revealed that 68.6% of the patients had FSD and that 55.9% of the patients never had sexual intercourse with their partners after surgery. Age, followed by time after surgery, radiotherapy, and consultation, was significantly correlated with FSD. The median score of the FACT-G was 86 (range, 41-108). Chemotherapy and marital status were found to significantly impair physical and social/family well-being, respectively (P < 0.05), and monthly income was identified as a factor that significantly affected the total FACT-G scores. CONCLUSION: The risk factors associated with FSD and QOL need to be studied in greater detail. Prospective researches that evaluate the effects of clinical psychological intervention on sexual function may be needed in the future.

The Feasibility of Conservative Management for Morbidly Adherent Placenta Accidentally Encountered after Vaginal Delivery.

OBJECTIVE: To evaluate the feasibility of conservative management for patients with morbidly adherent placenta (MAP) accidentally encountered after term vaginal delivery. METHODS: Medical records of patients with MAP who were accidentally encountered after term vaginal delivery and treated in our hospital from January 2009 to December 2015 were retrospectively reviewed. RESULTS: A total of 8 eligible patients were included in this analysis. Primary postpartum hemorrhage occurred in 5 (62.5%) cases. Emergent uterine artery embolization, intrauterine balloon occlusion, and blood transfusion were performed in 5 (62.5%), 2 (25%), and 2 (25%) cases, respectively. Placentas were left in situ in all these 8 cases. Subsequent adjunctive medication treatments, including methotrexate, mifepristone, and traditional Chinese medicine, were administered in 7 (87.5%), 4 (50%), and 3 (37.5%) cases, respectively. The retained placenta spontaneously passed out in 4 (50%) patients. Additional curettage operation was performed in 3 (37.5%) patients. Emergent hysterectomy was performed in 1 (12.5%) patient due to cardiac insufficiency and acute pulmonary edema caused by sepsis. No other severe adverse events were identified. CONCLUSIONS: Conservative management is feasible for patients with MAP accidentally encountered after vaginal delivery with close follow-up.

Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy.

Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and tumoural heterogeneity (TH) has been blamed for treatment failure. The genomic and epigenomic atlas of EOC varies significantly with tumour histotype, grade, stage, sensitivity to chemotherapy and prognosis. Rapidly accumulating knowledge about the genetic and epigenetic events that control TH in EOC has facilitated the development of molecular-targeted therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors, designed to target homologous recombination, are poised to change how breast cancer susceptibility gene (BRCA)-related ovarian cancer is treated. Epigenetic treatment regimens being tested in clinical or preclinical studies could provide promising novel treatment approaches and hope for improving patient survival.

Occult invasive cervical cancer after simple hysterectomy: a multi-center retrospective study of 89 cases.

BACKGROUND: Occult invasive cervical cancer (OICC) is sometimes incidentally found in surgical specimens after a simple hysterectomy (SH). This study was aimed at identifying a subset of patients with OICC who have a favorable prognosis. This patient group may not require adjuvant radiotherapy and other procedures. METHODS: The medical records of women in whom OICC was detected after an inadvertent SH were retrospectively reviewed. The relevant data, including clinicopathological characteristics, treatment and clinical outcome were evaluated. The primary and secondary endpoints were overall survival (OS) and relapse-free survival (RFS), respectively. RESULTS: Eighty-nine patients who met the inclusion criteria were included for analysis, and the risk of OICC was found to be 1.9 %. Finding an invasive cancer in a hysterectomy specimen after a conization procedure that shows positive margins was the most common reason (41.6 %) for the performance of inadvertent SH. In the univariate analysis, a tumor width > 20 mm, deep stromal invasion, and lymph node metastasis (LNM) were adversely associated with relapse (P < 0.001, < 0.001, and = 0.001, respectively) and survival (P = 0.003, 0.004, and 0.027, respectively), although these parameters were not independently associated with patient prognoses in the multivariate analysis. In patients with a tumor width ≤ 20 mm and superficial stromal invasion in the observation subgroup, the 5-year RFS and 5-year OS were both 100 %, whereas they were 57.1 % and 66.7 %, respectively, in patients with a tumor size > 20 mm and deep stromal invasion in the radiotherapy or chemotherapy subgroup (P < 0.001, and = 0.008, respectively). CONCLUSIONS: Simple observation after a lymphadenectomy procedure may be feasible in OICC patients with a tumor width ≤ 20 mm, superficial stromal invasion, a negative section margin in hysterectomy specimens, and no LNM.

Prognostic value of endometriosis in patients with stage I ovarian clear cell carcinoma: Experiences at three academic institutions.

OBJECTIVES: To investigate the prognostic value of endometriosis in patients with stage I ovarian clear cell carcinoma (OCCC). METHODS: The medical records of patients with stage I OCCC who had undergone complete staging surgery followed by systemic chemotherapy were retrospectively reviewed. RESULTS: A total of 237 women were included in this study. Univariate analysis revealed that the patients with endometriosis-associated ovarian carcinoma (EAOC) had significantly improved recurrence-free survival (RFS) and overall survival (OS) than those without EAOC (5-year RFS: 91.4% vs. 73.0%, respectively, and 5-year OS: 97.5% vs. 89.9%). However, EAOC was not identified as a significant prognostic predictor in multivariate analysis. The potential risk factors determined to be associated with EAOC included the pretreatment CA-125 level, FIGO stage, lymphovascular space invasion (LVSI), and menopausal status (P<0.001, P=0.0031, P=0.020, and P=0.038, respectively). CONCLUSIONS: Endometriosis was not independently associated with the prognosis of the OCCC patients, even when the tumor was confined to stage I. However, the intrinsic relationship between endometriosis and OCCC warrants further investigation.

Ovary and uterus-sparing procedures for low-grade endometrial stromal sarcoma: a retrospective study of 153 cases.

OBJECTIVE: To discuss the optimal treatment options for low grade endometrial stromal sarcoma (LG-ESS). METHODS: Medical records of consecutive patients with LG-ESS in our institute were collected. The pertinent data, including clinicopathological characteristics, treatment and prognostic information were evaluated. RESULTS: A total of 153 cases of LG-ESS were included. The 5-year relapse free survival (RFS), overall survival (OS) and survival after relapse (SAR) rates were 66.1%, 95.8% and 82.9%, respectively. Ovary-sparing procedures, positive resection-margins, and myomectomy were the independent adverse factors for relapse (P<0.0001, =0.0041, and =0.0075, respectively). Post-menopause, cervical involvement, and positive lymphovascular space involvement were significantly associated with survival (P<0.0001, =0.0020, and =0.0163, respectively). Distance recurrence and macroscopically residual tumors negatively affected SAR (P=0.0137 and =0.0004, respectively). No benefit was found for lymphadenectomy in terms of both RFS and OS (P=0.1187 and =0.5138, respectively). Initial ovary-sparing procedures and myomectomy had no impact on OS (P=0.0810 and =0.8845, respectively). Adjuvant treatment had a slightly beneficial effect both on OS and SAR. CONCLUSION: Hysterectomy with bilateral salpingo-oophorectomy and complete resection of the macroscopic lesion should be treated as the initial and salvage mainstay treatments for LG-ESS patients. Ovary-sparing procedures could be considered for young women without cervical involvement; however, long-term follow-up should be mandatory. Myomectomy should only be conserved for young patients with a strong desire for future fertility, with fully informed consent; hysterectomy was recommended after the completion of pregnancy and delivery. However, the roles of lymphadenectomy and adjuvant treatment deserve further investigation.

Comparison of pure and mixed-type clear cell carcinoma of the ovary: a clinicopathological analysis of 341 Chinese patients.

OBJECTIVE: This study aimed to analyze the clinicopathological features of pure and mixed-type ovarian clear cell carcinoma (CCC) in Chinese patients. METHODS: Patients with ovarian CCC treated in our institution between 1982 and 2012 were identified by reviewing the database and medical charts. Patients were assigned into 2 groups based on histology (pure or mixed). Comparison of clinicopathological parameters was performed to determine the similarities and/or differences between pure and mixed CCC. Kaplan-Meier model was used in survival analysis. RESULTS: Of 341 patients with ovarian CCC, 46 (13.5%) mixed tumors were identified, and the most common combination was clear cell/endometrioid, accounting for 56.5%. Patients with mixed-type CCC tended to have higher level of serum cancer antigen 125 (P = 0.023) and advanced tumor stage (P = 0.001). No difference was observed in other features including age, tumor size, residual disease, lymph node metastasis, and coexisting endometriosis. Tumor recurrence occurred in 47.8% and 58.1% in patients with pure and mixed histology, respectively (P = 0.209). Two groups had comparable platinum-sensitive disease (42.1% in pure and 44.0% in mixed type, P = 0.860). Patients with pure CCC had an improved median survival (105 vs 56 months), although statistical significance was not achieved. Histology subclassification of mixed tumor revealed that patients with clear cell/endometrioid histology had better survival outcome than those with clear cell/serous type (median survival, 140 vs 43 months, P = 0.004; median progression-free survival, 49 vs 12 months, P = 0.001). CONCLUSIONS: Patients with mixed CCC tended to have elevated serum cancer antigen 125 and advanced tumor stage. However, no significant difference was observed between the pure and mixed tumors regarding prognosis.

MicroRNA 421 induces the formation of high-invasive cell subsets of ovarian cancer from low-invasive cell subsets mediated by exosomes by activating the PI3K/AKT pathway.

Intratumoral heterogeneity (ITH) results in treatment failure in ovarian cancer (OC). Exosomes are related to the formation of a heterogeneous tumor microenvironment, and microRNAs play a crucial role in the progression of OC. Therefore, we aimed to explore the effect of exosomes and microRNA 421 (miR-421), which is mediated by exosomes, on ITH and the diagnosis of OC. Exosomes derived from A2780 cells with the highest (AHC) or lowest (ALC) invasive/migratory capacity cells (AHE/ALE) were extracted by differential centrifugation. We conducted a series of experiments to verify the role of AHE and miR-421 in promoting the transformation of low-invasive cells to high-invasive cells by regulating the PI3K/AKT pathway, and we also measured the levels of CA125 in serum exosomes. The results of assays showed that the AHE and miR-421, mediated by exosomes, significantly increased the malignancy of ALC cells by activating the PI3K/AKT pathway. The expression of miR-421 was significantly increased in the serum exosomes derived from high-grade serous ovarian cancer (HGSOC) patients. Our findings indicate that MiR-421, mediated by exosomes, could induce the transformation of highly invasive cell subpopulations from subpopulations of OC cells with low invasive potential by activating the PI3K/AKT signaling pathway.