Current research of Assisted Reproductive Technology for women with early endometrial cancer and atypical endometrial hyperplasia after conservative treatment.

As the incidence of endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) has been increasing, and has shown young trend. It is crucial to study the fertility-preserving treatment of endometrial lesions and fertility-promoting protocols. Age, obesity, and irregular ovulation are not only high-risk factors for endometrial lesions but also key factors affecting female fertility. Assisted reproductive technology (ART) can significantly improve pregnancy outcomes in patients with AEH and EC after conservative treatment. Based on the existing studies, this article reviews the progress of research on pregnancy outcomes of ART and its influencing factors in such patients. It helps physicians in providing optimal fertility guidance.

Metabolic disorders sensitise endometrial carcinoma through endoplasmic reticulum stress.

BACKGROUND: Metabolic disorder is considered a well-established risk factor for endometrial carcinoma (EC). However, the mechanism remains unclear. Insulin resistance and excessive flux of free fatty acids serve as fundamental pathogenic factors in metabolic disorders, including obesity and type 2 diabetes. The aim of this study was to test the correlation between insulin resistance and dyslipidaemia in EC and to determine the effect of insulin and saturated fatty acids on EC cells. METHODS: A retrospective study on the medical records of patients with EC and RNA-seq from the TCGA database analysed with edgR and Gene Ontology (GO) were used to assess the correlation of dyslipidaemia and diabetes as well as obesity. Crystal violet assays and CCK-8 assays were used to detect the proliferation of EC cells, and Annexin V-PI was used to examine apoptosis. Transient changes in mitochondrial Ca2+ and reactive oxygen species (ROS) were monitored via confocal microscopy. DNA damage was assessed by comet assays. Changes in signalling pathways were detected via phospho-kinase array. western blotting was used to assess the molecular changes in endoplasmic reticulum (ER) stress and DNA damage. RESULTS: We found that glucose metabolism disorders accompanied dyslipidaemia in patients with EC. As a key regulator of glucose metabolism disorders, insulin promoted DNA damage, ROS and Ca2+ homoeostasis imbalance in a panel of established EC cell lines. Interestingly, excessive insulin boosted saturated fatty acid-induced pro-apoptotic effects in EC cells. Furthermore, our data showed that insulin synergised with saturated fatty acids to activate the mechanistic target of rapamycin kinase/70 kDa ribosomal protein S6 kinase (mTOR/p70S6K) pathway and ER stress, resulting in Ca2+ release from ER and unfolded protein response (UPR) activation, which contributed to combined insulin and saturated fatty acid treatment-induced apoptosis and tumour progression. CONCLUSIONS: Our data are the first to illustrate that impaired glucose metabolism accelerates dyslipidaemia-promoted EC progression, which is attributed to hyperinsulinaemia and saturated fatty acid-induced Ca2+ dyshomoeostasis and UPR activation in EC cells via ER stress.

Estrogen-Induced Extracellular Calcium Influx Promotes Endometrial Cancer Progress by Regulating Lysosomal Activity and Mitochondrial ROS.

OBJECTIVE: Calcium is present in serum mainly in filterable and bound forms, and Ca2+ is a major key to modulate signaling pathways that control oncogenesis and oncochannels associated with several types of cancer. However, the biological significance of serum calcium and its related mechanism with estrogen in endometrial cancer (EC) still remains elusive. This study aims to ascertain the relationship between serum calcium and clinicopathology in EC. METHODS: Retrospective assessment of a total of 502 patients diagnosed with EC after surgery in Peking University People's Hospital from 2010 to 2018. Preoperative serum ionized calcium and the albumin corrected calcium was calculated in quartiles for various postoperative clinicopathological characteristics, logistic regression adjusted for potential confounders. Intracellular calcium homeostasis change induced by estrogen was detected by confocal analysis. Downstream pathways were analyzed by transcriptome and proteomics. Mitochondrial Ca2+ and ROS (reactive oxygen species) level was detected by confocal and flow cytometry. Lysosomal morphological and membrane changes were verified by confocal or Western blot assays. RESULTS: High level of albumin-corrected serum calcium was significantly correlated with EC clinicopathological characteristics progression include lymph vascular space invasion, lymph nodes metastasis, myometrial invasion, and cervical invasion. Calcium homeostasis regulated by estrogen in EC cells derived from extracellular calcium influx but not the release of the endoplasmic reticulum. Proteomic and bioinformatic analysis revealed the calcium influx might be involved in the regulation of autophagy and mitochondrial-related pathways. Mechanistic investigation demonstrated that calcium influx acted on the function of mitochondrial ROS and lysosomal activity. CONCLUSION: Our findings revealed that serum calcium level was significantly related to poor outcomes. The extracellular calcium influx induced by estrogen was targeted to mitochondrial ROS and lysosome activity, which should be oriented to improve EC therapeutic strategies.

Comparison of prognosis of patients with endometrial cancer after hysteroscopy versus dilatation and curettage: A multicenter retrospective study.

Introduction: Hysteroscopy is a useful procedure for diagnosing endometrial cancer. There is controversy regarding whether hysteroscopy affects the prognosis of endometrial cancer by prompting cancer cell into intraperitoneal dissemination. Our purpose was to confirm whether hysteroscopy could be a risk factor of the tumor stage, recurrence and survival rate of endometrial cancer. Methods: This multicenter retrospective study included all consecutive patients who had endometrial carcinoma diagnosed preoperatively with hysteroscopy and directed endometrial biopsy (HSC, group A) and dilatation and curettage (D&C, group B) between February 2014 and December 2018 at the Fujian Provincial, China. We compared the demographic feature, clinical characteristics and prognosis between the two groups. Results: A total of 429 patients were included in the study (Group A, n = 77; Group B, n = 352). There was no significant difference between their baseline characteristics [including age, BMI, histological type and International Federation of Gynecology and Obstetrics (FIGO) stage]. By comparing several pathological conditions that may affect prognosis, there were no significant differences between the two groups in the peritoneal cytology, depth of myometrial invasion, the positivity of lymph nodes, lymphovascular space invasion and paraaortic lymph node dissection. Finally, no significant difference was found between the two groups in overall survival (OS) (P = 0.189) or recurrence free survival (RFS) (P = 0.787). Conclusion: Under certain inflation pressure and distension medium, hysteroscopic examination and lesion biopsy ensure the safety and have no adverse effects on prognosis compared to conventional curettage.

Serum calcium is a novel parameter to assess metabolic syndrome in endometrial carcinoma.

OBJECTIVES: To investigate the distribution of serum calcium and the relationship between serum calcium and serum metabolic parameters in endometrial carcinoma (EC) patients. METHODS: Retrospective assessment of patients diagnosed with endometrial cancer from Peking University People's Hospital from 2004 to 2009. Clinical characteristics as well as pretreatment serum calcium, albumin, fasting plasma glucose (FPG), serum triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol (TC) value were extracted from patient records. Serum calcium was corrected for albumin. Unpaired t test and analysis of covariance were used to compare serum calcium among categorical variables. Simple correlation analyses and partial correlation analyses were used to assess the associations between serum calcium and continuous variables. RESULTS: Two-hundred twenty patients were included in this study. After adjusting for confounders, postmenopausal patients had higher total serum calcium (p=0.002) and albumin-corrected serum calcium (p=0.012) than premenopausal patients, endometrioid endometrial carcinoma (EEC) patients had higher total serum calcium than non-endometrioid endometrial carcinoma (NEEC) patients (p=0.037). Significant positive correlations were found between total serum calcium and FPG (p=0.017), TG (p=0.043), HDL (p=0.042), LDL (p<0.001), and TC (p<0.001) after adjusting for multiple variables, and the corrected serum calcium showed no significant correlation with metabolic parameters. CONCLUSION: Total serum calcium might be a more sensitive parameter for metabolic syndrome in endometrioid endometrial cancer patients than lipids.

Vaginectomy and vaginoplasty for isolated vaginal recurrence 8 years after cervical cancer radical hysterectomy: A case report and literature review.

A subgroup of early-stage cervical cancer patients suffer from vaginal cuff recurrence following a primary surgery; however, recurrence after a disease-free interval of 5 years is rare. Treatments for isolated vaginal relapse remain controversial. Here we report a case of a 50-year-old woman with isolated vaginal cuff recurrence 8 years after primary radical surgery for cervical cancer. We conducted a vaginectomy and vaginoplasty using a type of tissue-engineered biomaterial graft. Three chemotherapy cycles of paclitaxel and cisplatin were administered after surgery. The patient has no evidence of disease to date (18 months after surgery) and had regained a satisfactory sexual life by 8 months postoperatively. To our knowledge, this case represents the first report regarding the use of vaginoplasty with biomaterial graft following vaginectomy for late isolated vaginal recurrence of cervical cancer in a patient who had undergone a primary radical hysterectomy.

Gefitinib enhances sensitivity of endometrial cancer cells to progestin therapy via dual-specificity phosphatase 1.

In this study, we investigated if Gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, augments endometrial cancer (EC) therapy with medroxyprogesterone acetate (MPA). Combined treatment with Gefitinib plus MPA decreased the proliferation and invasiveness of the Ishikawa and RL952 EC cell lines more effectively than MPA treatment alone. Moreover, combined treatment with Gefitinib plus MPA reduced growth of EC xenografts in Balb/c nude mice more than either Gefitinib or MPA alone. The therapeutic efficacy of combined Gefitinib plus MPA treatment was dependent on expression of dual-specificity phosphatase 1 (DUSP1). DUSP1 knockdown in Ishikawa cells treated with Gefitinib plus MPA showed greater proliferation and invasiveness than parental Ishikawa cells treated similarly. EC cells treated with the combination of Gefitinib plus MPA also showed DUSP1-dependent reductions in phospho-ERK1/2 and increases in E-Cadherin. Thus, Gefitinib appears to DUSP1-dependently enhance the therapeutic efficacy of progestin in EC cells.

Comparison of Survival Benefits of Combined Chemotherapy and Radiotherapy Versus Chemotherapy Alone for Uterine Serous Carcinoma: A Meta-analysis.

OBJECTIVE: To date, there is no convincing evidence comparing the impact of combined chemotherapy and radiotherapy with chemotherapy alone in postoperative uterine serous carcinoma (USC), which remains an unclear issue. We conducted a meta-analysis assessing the impact of combined chemotherapy and radiotherapy compared to chemotherapy alone on overall survival in postoperative USC. METHODS: A comprehensive search was performed in the databases of EMBASE, PubMed, Web of Science, and Cochrane Library from inception to March 2016. Studies comparing survival among patients who underwent combined chemotherapy and radiotherapy or chemotherapy alone after surgery for USC were included. Quality assessments were carried out by the Newcastle-Ottawa Scale. Hazard ratio (HR) for overall survival was extracted, and a random-effects model was used for pooled analysis. Publication bias was assessed using both funnel plot and the Egger regression test. Statistical analyses were performed using Stata version 13.0 software. RESULT: Nine retrospective studies with relatively high quality containing 9354 patients were included for the final meta-analysis. The pooled results demonstrated that combined chemotherapy and radiotherapy significantly reduced the risk of death (HR, 0.72; P < 0.0001) compared to chemotherapy alone with a low heterogeneity (I = 21.0%, P = 0.256). Subgroup analyses indicated that calculating HR by unadjusted method may cause the heterogeneity among studies. Exploratory analyses showed that either patients with early stage disease (HR, 0.73; P = 0.011) or advanced stage disease (HR, 0.80; P < 0.0001) have survival benefits from combined chemotherapy and radiotherapy. No significant evidence of publication bias was found. CONCLUSIONS: This is the first meta-analysis examining the role of combined chemotherapy and radiotherapy compared to chemotherapy alone in USC. Our results suggest the potential survival benefits of combined chemotherapy and radiotherapy. Further studies, preferably randomized clinical trials, are needed to confirm our results.

Trends in computed tomography utilisation in the emergency department: A 5 year experience in an urban medical centre in northern Taiwan.

BACKGROUND: Steady increase in computed tomography (CT) utilisation in the ED was observed in countries such as the USA, Canada, China and Korea; however, limited empirical data are available regarding Taiwan. OBJECTIVE: The objective of the present study is to quantify and compare trends in CT utilisation in the ED over a 5 year period in a medical centre in Taiwan. METHODS: Electronic chart review was performed in a medical centre with an annual ED census of 80 000 patients. Subjects >20 years of age who underwent CT scans during ED visits from 1 January 2005 to 31 December 2009 were identified. RESULTS: Among the 333 673 adult ED visits, 43 635 received CT scans, with a utilisation rate of 131 per 1000. Within the 5 year span, patient volume increased by 7.7%, whereas CT utilisation increased by 42.7%. The rates of increase in patient volume and CT utilisation were 5.0% and 32.4% in non-trauma; 19.7% and 97.8% in trauma. CT scans were mostly performed on the head (47%), abdomen (36%), followed by chest (10%) and miscellaneous (7%). An increase of 168% in spinal CTs for trauma patients was observed. An increase in CT utilisation was found in all age groups with a proportionate increase with increasing age in both trauma and non-trauma. CONCLUSION: ED CT utilisation has increased at a rate far exceeding the growth in ED patient volume. This may be attributed to the improved utility of CT in diagnosing serious pathology, more diagnostic indications for CT, ready availability and the necessity for diagnostic certainty in the ED.

Prognostic factors for survival outcome after in-hospital cardiac arrest: An observational study of the oriental population in Taiwan.

BACKGROUND: In-hospital cardiac arrest (IHCA) is a catastrophic complication for patients while admitted in a medical institution. The outcome of IHCA remains poor, and understanding of the prognostic factors for survival outcome after IHCA is lacking, specifically in an oriental population. METHODS: A retrospective observational cohort study of 382 patients with IHCA who required resuscitation was conducted in an urban tertiary hospital in Taiwan. Return of spontaneous circulation (ROSC) and survival to hospital discharge were the primary outcome measures. RESULTS: The incidence of IHCA was 3.25 per 1000 admissions. These patients had a mean age of 67.2 ± 21.7 years and were mostly men (66.5%). The rate of successful ROSC was 66%, and the rate of survival to hospital discharge was 11.8%. A stepwise decrease in ROSC was observed with additional resuscitation efforts. Independent predictors for survival to hospital discharge were being female, a resuscitation duration of <20 minutes, and no use of epinephrine during resuscitation. A 68% ROSC success rate and an 84% survival to discharge rate was recorded in patients receiving resuscitation for <30 minutes. Young patients seemed the most likely to benefit from longer resuscitation attempts (>30 minutes), as observed in survival to hospital discharge. CONCLUSION: Based on data from a single hospital registry in East Asia, a shorter duration of resuscitation was demonstrated to be a predictor of immediate survival with ROSC and survival to hospital discharge.