Neoadjuvant chemotherapy plus camrelizumab for locally advanced cervical cancer (NACI study): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Locally advanced cervical cancer constitutes around 37% of cervical cancer cases globally and has a poor prognosis due to limited therapeutic options. Immune checkpoint inhibitors in the neoadjuvant setting could address these challenges. We aimed to investigate the efficacy and safety of neoadjuvant chemo-immunotherapy for locally advanced cervical cancer. METHODS: In this single-arm, phase 2 trial, which was done across eight tertiary hospitals in China, we enrolled patients aged 18-70 years with untreated cervical cancer (IB3, IIA2, or IIB/IIIC1r with a tumour diameter ≥4 cm [International Federation of Gynecology and Obstetrics, 2018]) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients underwent one cycle of priming doublet chemotherapy (75-80 mg/m2 cisplatin, intravenously, plus 260 mg/m2 nab-paclitaxel, intravenously), followed by two cycles of a combination of chemotherapy (cisplatin plus nab-paclitaxel) on day 1 with camrelizumab (200 mg, intravenously) on day 2, with a 3-week interval between treatment cycles. Patients with stable disease or progressive disease received concurrent chemoradiotherapy, and patients with a complete response or partial response proceeded to radical surgery. The primary endpoint was the objective response rate, by independent central reviewer according to Response Evaluation Criteria in Solid Tumours, version 1.1. Activity and safety were analysed in patients who received at least one dose of camrelizumab. This study is registered with ClinicalTrials.gov, NCT04516616, and is ongoing. FINDINGS: Between Dec 1, 2020, and Feb 10, 2023, 85 patients were enrolled and all received at least one dose of camrelizumab. Median age was 51 years (IQR 46-57) and no data on race or ethnicity were collected. At data cutoff (April 30, 2023), median follow-up was 11·0 months (IQR 6·0-14·5). An objective response was noted in 83 (98% [95% CI 92-100]) patients, including 16 (19%) patients who had a complete response and 67 (79%) who had a partial response. The most common grade 3-4 treatment-related adverse events during neoadjuvant chemo-immunotherapy were lymphopenia (21 [25%] of 85), neutropenia (ten [12%]), and leukopenia (seven [8%]). No serious adverse events or treatment-related deaths occurred. INTERPRETATION: Neoadjuvant chemo-immunotherapy showed promising antitumour activity and a manageable adverse event profile in patients with locally advanced cervical cancer. The combination of neoadjuvant chemo-immunotherapy with radical surgery holds potential as a novel therapeutic approach for locally advanced cervical cancer. FUNDING: National Key Technology Research and Development Program of China and the National Clinical Research Center of Obstetrics and Gynecology.

NLRP12 is a prognostic biomarker and correlated with immune infiltrates in epithelial ovarian cancer.

BACKGROUND: NLRP12 is a member of the intracellular Nod-like receptor (NLR) family, suggesting it is an innate immune receptor for the initiation and progression of several cancers. However, its role on prognosis and immune infiltrates in epithelial ovarian cancer (EOC) is still unknown. The present study aimed to evaluate its prognostic value and its association with immune infiltrates in EOC. METHODS: The mRNA expression of NLRP12 of EOC from The Cancer Genome Atlas (TCGA) was analyzed. The association between NLRP12 and clinicopathological characters was evaluated with logistic regression. The association between NLRP12 expression and survival was analyzed by Cox regression and Kaplan-Meier analyses. A nomogram was used to predict the impact of NLRP12 on prognosis. Gene Ontology term analysis and gene set enrichment analysis (GSEA) were performed to identify the signaling pathways related to NLRP12 expression. Immune cells infiltration for NLRP12 was analyzed using single-sample GSEA. The relationship between NLRP12 and tumor-infiltrating immune cells (TICs) was investigated by a Wilcoxon rank sum test. The expression of NLRP12 were also further verified in EOC tissues and cell lines. Additionally, we confirmed the biological function of NLRP12 in vitro. RESULTS: NLRP12 was highly expressed in patients with EOC from TCGA. High NLRP12 expression correlated with poor disease-specific survival (p < 0.001) and overall survival (p < 0.001). Multivariate analysis revealed that NLRP12 expression was an independent prognostic marker for overall survival (p = 0.042). The C-indexes and calibration plots of the nomogram based on multivariate analysis indicated an effective predictive performance for EOC patients. GSEA showed enrichment of cell adhesion, tumorigenesis and immune response in the NLRP12 high expression group. Increased NLRP12 expression correlated positively with several TICs, including macrophages, neutrophils, T effector memory cells and immature dendritic cells (p < 0.001). In addition, NLRP12 silencing inhibited cell proliferation and migration in EOC cells. CONCLUSIONS: In conclusion, increased NLRP12 expression correlated significantly with poor survival and immune infiltration in EOC.

Prediction of complete regression in fertility-sparing patients with endometrial cancer and apical hyperplasia: the GLOBAL model in a large Chinese cohort.

BACKGROUND: Fertility preservation treatment is increasingly essential for patients with apical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) worldwide. Complete regression (CR) is the main endpoint of this treatment. Accurately predicting CR and implementing appropriate interventions during treatment are crucial for these patients. METHODS: We conducted a retrospective study involving 193 patients diagnosed with atypical AEH or EEC, enrolled from January 2012 to March 2022 at our center. We evaluated 24 clinical parameters as candidate predictors and employed LASSO regression to develop a prediction model for CR. Subsequently, a nomogram was constructed to predict CR after the treatment. We evaluated the performance of the nomogram using receiver operator characteristic (ROC) curve and decision curve analysis (DCA) to assess its predictive accuracy. Additionally, we employed cumulative curves to determine the CR rate among patients. RESULTS: Out of the 193 patients, 173 achieved CR after undergoing fertility preservation treatment. We categorized features with similar properties and provided a list of formulas based on their coefficients. The final model, named GLOBAL (including basic information, characteristics, blood pressure, glucose metabolism, lipid metabolism, immunohistochemistry, histological type, and medication), comprised eight variables identified using LASSO regression. A nomogram incorporating these eight risk factors was developed to predict CR. The GLOBAL model exhibited an AUC of 0.907 (95% CI 0.828-0.969). Calibration plots demonstrated a favorable agreement between the predicted probability by the GLOBAL model and actual observations in the cohort. The cumulative curve analysis revealed varying cumulative CR rates among patients in the eight subgroups. Categorized analysis demonstrated significant diversity in the effects of the GLOBAL model on CR among patients with different total points (p < 0.05). CONCLUSION: We have developed and validated a model that significantly enhances the predictive accuracy of CR in AEH and EEC patients seeking fertility preservation treatment.

The comparison of pure uterine serous carcinoma and mixed tumor with serous component: a single-institution review of 91 cases.

BACKGROUND: Pure uterine serous carcinoma (p-USC) and mixed tumors with serous component (m-USC) are aggressive subtypes of endometrial cancer associated with high mortality rates. This retrospective study aimed to compare clinicopathologic features and outcomes of p-USC and m-USC in a single center. METHODS: This study retrospectively reviewed patients diagnosed with USC at Peking University People's Hospital between 2008 and 2022. T-tests and chi-square tests were used to compare clinicopathological characteristics between p-USC and m-USC. Kaplan-Meier survival curve and Cox regression analysis were used to analyze the impact of clinical and pathological variables on OS and PFS. RESULTS: Among the 91 patients who underwent surgery, 65.9% (n = 60) were p-USC, and 34.1% (n = 31) were m-USC. Patients with p-USC had earlier menopause (P = 0.0217), a lower rate of progesterone receptor(PR) expression (P < 0.001), and were more likely to have positive peritoneal cytology (P = 0.0464). After a median follow-up time of 40 months, 28 (46.7%) p-USC and 9 (29%) m-USC patients had progression disease, 18 (30%) and 8 (25.8%) patients died of their disease. 5-year PFSR were 51.2% and 75.3%, respectively, and 5-year OS rates were 66% and 67.4%. Kaplan-Meier survival analysis showed that p-USC was more likely to relapse than m-USC (P = 0.034), but there was no significant difference in OS. Cox regression analysis showed that lymph node metastasis and surgical approach were risk factors for OS, and myoinvasion depth ≥ 1/2 was an independent risk factor for PFS. CONCLUSIONS: p-USC was more likely to relapse than m-USC, but there was no significant difference in OS between the two subtypes.

DEAR model in overweight endometrial cancer patients undergoing fertility-sparing treatment: A randomized controlled trial.

OBJECTIVE: To evaluate the effects of DEAR weight management in overweight patients undergoing fertility-sparing treatment for endometrial cancer or atypical hyperplasia. METHODS: Women with endometrial cancer or atypical hyperplasia who received fertility-sparing treatment and had a body mass index of >25 kg/m2 were randomly allocated to the DEAR (DEAR weight management) and control (self weight management) groups. Body morphology and composition, glycolipid metabolism, and tumor outcomes were assessed in both groups before and at 3 and 6 months after intervention. RESULTS: Overall, 72 subjects were included (36 in each group). Following intervention, the DEAR group showed significantly lower median body weight (69.45 vs. 78.05), body mass index (26.19 vs. 29.15), lipid accumulation index (29.21 vs. 57.86), body fat mass (24.00 vs. 29.30), visceral fat area (112.5 vs. 133.3), and glycolipid metabolic indices (except high density lipoprotein) than the control group (P < 0.05) and showed a decreasing trend. The test group achieved significantly higher complete remission (88.46% vs. 57.14%; P < 0.05); the time to complete remission did not differ significantly (P > 0.05). CONCLUSIONS: DEAR weight management can improve the studied parameters and complete remission rates in this population. REGISTRATION: NCT06169449.

Pre- vs Post-Operative Levator Ani Subtended Volume in Patients Undergoing Hysterectomy: A Comparative Imaging Study.

INTRODUCTION AND HYPOTHESIS: The effects of hysterectomy on pelvic floor function remain uncertain, with the levator ani muscle (LAM) playing a critical role in pelvic support. The levator ani subtended volume (LASV) is an objective measure of the LAM's anatomical volume, derived from magnetic resonance imaging (MRI). This study was aimed at assessing the consistency between MRI and computed tomography (CT) in quantifying LASV, and to investigate the effect of hysterectomy on the LAM. METHODS: This retrospective study analyzed a cohort of 55 hysterectomy patients, utilizing pre-operative pelvic MRI and post-operative CT scans to measure the LASV. To evaluate the consistency between MRI and CT, the study employed the intraclass correlation coefficient and Bland-Altman agreement analysis in a subset of 32 patients with both pre-operative scans. A paired-samplet test was used to analyze LASV changes pre- and post-hysterectomy, and linear regression analysis was performed to account for potential risk factors that may influence post-operative LASV. RESULTS: High consistency between MRI and CT in measuring LASV was found, with an ICC of 0.911. We observed a significant increase in LASV following hysterectomy, with mean volume pre- and post-operatively of 16.66 cm3 and 18.87 cm3 respectively. Age and body mass index were significant predictors of post-hysterectomy LASV, whereas parity and the type of hysterectomy had no significant impact. CONCLUSIONS: Hysterectomy significantly affects the LAM, resulting in an increase in post-operative LASV. Moreover, this study verifies that MRI and CT can be used interchangeably for LASV measurements in clinical practice.

A retrospective study of ovarian tissue cryopreservation in female patients with hematological diseases for fertility preservation.

PURPOSES: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. METHODS: We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. RESULTS: A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT. CONCLUSIONS: Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.

Prognostic significance of positive peritoneal cytology in endometrial carcinoma based on ESGO/ESTRO/ESP risk classification: A multicenter retrospective study.

OBJECTIVE: This study aimed to determine the prognostic significance of positive peritoneal cytology (PC) on endometrial carcinoma (EC) patients under the ESGO/ESTRO/ESP risk classification. METHODS: This study retrospectively analyzed EC patients from 27 medical centers in China from 2000 to 2019. Patients were divided into three ESGO risk groups: low-risk, intermediate-risk and high-intermediate risk, and high-risk groups. The covariates were balanced by using the propensity score-based inverse probability of treatment weighting (PS-IPTW). The prognostic significance of PC was assessed by Kaplan-Meier curves and multivariate Cox regression analysis. RESULTS: A total of 6313 EC patients with PC results were included and positive PC was reported in 384 women (6.1%). The multivariate Cox analysis in all patients showed the positive PC was significantly associated with decreased PFS (hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.55-3.13, P < 0.001) and OS (HR 2.25, 95% CI 1.49-3.40, P < 0.001),and the Kaplan-Meier curves also showed a poor survival in the intermediate and high-intermediate risk group (5-year PFS: 75.5% vs. 93.0%, P < 0.001; 5-year OS: 78.3% vs. 96.4%, P < 0.001); While in the low-risk group, there were no significant differences in PFS and OS between different PC status (5-year PFS: 93.1% vs. 97.3%, P = 0.124; 5-year OS: 98.6% vs. 98.2%, P = 0.823); in the high-risk group, significant difference was only found in PFS (5-year PFS: 62.5% vs. 77.9%, P = 0.033). CONCLUSION: Positive PC was an adverse prognostic factor for EC, especially in the intermediate and high-intermediate risk patients. Gynecologic oncologists should reconsider the effect of positive PC on different ESGO risk groups.

Comparing carbon nanoparticles and indocyanine green for sentinel lymph node mapping in endometrial cancer: A randomized-controlled single-center trial.

BACKGROUND AND OBJECTIVES: To compare the feasibility and diagnostic value of sentinel lymph node (SLN) mapping with carbon nanoparticles (CNPs) and indocyanine green (ICG) in endometrial cancer (EC). METHODS: This was a single-center, open-label, randomized controlled trial. Between August 1, 2020 and April 30, 2022, patients with early-stage EC were assessed for enrollment. All patients underwent SLN mapping with ICG or CNPs ± pelvic and/or para-aortic lymphadenectomy. The detection rate (DR), its impact factors, the sensitivity and the negative predictive value (NPV) of SLN mapping were analyzed. RESULTS: In total, 206 patients, with 103 per group, were included. The overall and bilateral DRs of the two groups were comparable without significant differences. There was no difference regarding the distribution of mapped SLNs. The sensitivity was 66.7% for both groups, and the NPVs were not significantly different. Furthermore, the sensitivity and NPV reached 100% when calculated either per hemipelvis or only in patients with bilateral SLN detection. CONCLUSIONS: SLN mapping by CNPs in EC is feasible with high DRs and diagnostic accuracy compared with ICG. CNPs might be an alternative to ICG for SLN mapping when near-infrared imaging equipment is lacking, especially in stage IA patients.

A comparative analysis of cycle threshold (Ct) values from Cobas4800 and AmpFire HPV assay for triage of women with positive hrHPV results.

BACKGROUND: To compare the triage performance of HPV viral loads reflected by cycle threshold values (CtV) from two different HPV testing assays: the PCR based Cobas4800 and the isothermal amplification based AmpFire assay. METHODS: We used the data from a sub-study of The Chinese Multi-Center Screening Trial and analyzed the data of the cases positive in both Cobas4800 and AmpFire assays with recorded CtV. Spearman's correlation was applied to analyze the association between CtV from AmpFire and Cobas4800 assays, as well as the correlation between CtV and the histological lesion grades. The 50th percentile of CtV was used as the cutoff to construct triage algorithms for HPV-positive cases. McNemar's test was used to analyze the differences in sensitivity and specificity for detecting CIN2 + and CIN3 + in different triage algorithms. RESULTS: Four hundred forty-six HPV positive women who had consistent HPV results from Cobas4800 and AmpFire in terms of the HPV genotype and reported Ct values were included in the analysis. The mean CtV of hrHPV tested by Cobas4800 and AmpFire were linear correlated. Direct association were showed between the severity of cervical lesions and the HPV viral loads reflected by CtV of hrHPV, HPV16, non-16/18 hrHPV and A9 group from both assays. HPV16/18 genotyping combined with low-CtV for non-16/18 hrHPV, especially A9 group, were demonstrated to be satisfactory in the sensitivity and specificity for detecting CIN2 + or CIN3 + . CONCLUSION: Ct value represented a good triage marker in both PCR-based and isothermal amplification HPV detection.

A review of basic to clinical targeted therapy and immunotherapy in uterine serous cancer.

Uterine serous carcinomas show more frequent mutations of TP53, FBXW7, PIK3CA, and PP2R1A. Furthermore, cyclin-dependent kinase, human epidermal growth factor receptor 2, phosphatidylinositol 3-kinase/protein kinase B, and mammalian target of rapamycin signaling pathways are involved in uterine serous carcinoma progression. However, most patients with uterine serous carcinoma develop chemoresistance to paclitaxel and carboplatin. Moreover, uterine serous carcinoma shows immunosuppressive microenvironment with lower frequency of microsatellite instability. However, some clinical trials of human epidermal growth factor receptor 2/neu and WEE1 targeted therapies showed good effects in prolonging the survival in patients with uterine serous carcinoma. More effective targeted therapies and immunotherapies need to be developed in recurrent uterine serous carcinomas.

Help-seeking behavior for nonsevere stress urinary incontinence among elderly women in communities, Beijing, China.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is a common health problem and influences women's quality of life significantly. In order to enhance health education according to a specific situation, it is essential to identify barriers to seeking help among elderly women with nonsevere SUI. The objectives were to investigate reasons for (not) seeking help for nonsevere SUI among women aged ≥60 years, and to analyze factors affecting help-seeking behavior. METHODS: We enrolled 368 women aged ≥60 years with nonsevere SUI from communities. They were asked to filled out sociodemographic information, International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), Incontinence Quality of Life (I-QOL), and self-constructed questiones on help-seeking behavior. Mann-Whitney U tests were used to analyze the different factors between seeking group and nonseeking group. RESULTS: Only 28 women (7.61%) had ever sought help from health professionals for SUI. The most frequent reason for seeking help was urine-soaked clothes (67.86%, 19 out of 28). The most frequent reason for not seeking help was that women thought it was normal (67.35%, 229 out of 340). Compared with the nonseeking group, the seeking group had higher total ICIQ-SF scores and lower total I-QOL scores. CONCLUSION: Among elderly women with nonsevere SUI, the rate of seeking help was low. Lack of correct perception about the SUI kept women from doctor visits. Women who were bothered by more severe SUI and lower quality of life were more likely to seek help.

Gestational diabetes mellitus and pelvic floor function 6 weeks postpartum in Chinese women.

INTRODUCTION AND HYPOTHESIS: With the significant increase in its incidence, gestational diabetes mellitus (GDM) has received growing attention for its effect on pelvic floor function. This study was aimed at investigating the association of GDM with pelvic floor function and diastasis recti abdominis (DRA) in postpartum women. METHODS: This is a retrospective cohort study. At 6 weeks postpartum, 1,133 postpartum women with vaginal delivery underwent routine examinations including measurement of the pelvic floor muscle (PFM) strength and endurance, determination of the stress urinary incontinence (SUI) by questionnaire, quantification of pelvic organ prolapse (POP) and assessment of DRA. Statistical analysis was performed using binary logistic regression and multiple linear regression analysis. RESULTS: One hundred and seventy-six (176) of the 1,133 women were confirmed to be suffering from GDM, with a rate of 15.53% (176 out of 1,133). The age and pre-pregnancy body mass index of the GDM group were significantly higher than those without GDM (p < 0.05). The GDM group was more likely to have smaller gestational age and a higher chance of having to undergo a lateral episiotomy. No statistically significant differences are found in PFM endurance (B: -0.025, p = 0.462) or PFM strength (B: -0.001, p = 0.979) between women with and without GDM. And these two groups are not significantly different in terms of the prevalence of SUI (19.3% vs 20.4%), POP (35.8% vs 37.5%) and DRA (29.0% vs 25.8%; p > 0.05). CONCLUSIONS: Pelvic floor muscle function and SUI/POP/DRA prevalence of women at 6 weeks postpartum are not significantly affected by GDM.

Analysis of immunohistochemical characteristics and recurrence after complete remission with fertility preservation treatment in patients with endometrial carcinoma and endometrial atypical hyperplasia.

OBJECTIVE: To investigate the relationship between immunohistochemical characteristics and recurrence after complete remission (CR) with fertility preservation treatment in patients with endometrial cancer (EC) and endometrial atypical hyperplasia (AH). METHODS: The clinical data and immunohistochemical results of 53 patients with EC and 68 patients with AH admitted to Peking University People's Hospital from January 2010 to January 2021 were retrospectively analyzed. Patients were divided into two groups according to whether recurrence after complete remission (CR): group 1: recurrence after CR; group 2: no recurrence after CR, for statistical analysis. RESULTS: (1) The expression rate of ER in group 1 was lower than that in group 2, (P < 0.05). The expression rate of Ki-67 in group 1 was significantly higher than that in group 2, (P < 0.01). The expression rates of PR, P16, P53, and PTEN were not significantly different between the two groups (P > 0.05); (2) combination index ER/ Ki-67 row ROC curve analysis, there was a significant difference (P < 0.01), the best cut-off value was 3.55, sensitivity 0.730, specificity 1.000, Youden index 0.730. The 3-year RFS of high rate patients was 100%, and that of low rate patients was 42.3%, P < 0.01. CONCLUSIONS: The expression rate of Ki-67 is of great significance in predicting the recurrence of EC after fertility preservation therapy. The best cut-off value of combination index ER/ Ki-67 (3.55) was better than a single immunohistochemical marker in predicting recurrence of EC after fertility preservation treatment.

Comparison of sentinel lymph node distribution and lymphatic drainage pathway between high- and low-risk endometrial cancers.

PURPOSE: This study aimed to compare the distribution and drainage pathway of sentinel lymph nodes between high- and low-risk endometrial cancers. METHODS: In total, 429 patients with endometrial cancer who underwent sentinel lymph node biopsy in Peking University People's Hospital from July 2015 to April 2022 were retrospectively enrolled. There were 148 patients in the high-risk group and 281 patients in the low-risk group. RESULTS: The unilateral and bilateral detection rates of sentinel lymph nodes were 86.5% and 55.9%, respectively. The highest detection rate was achieved in the subgroup with a combined use of indocyanine green (ICG) and carbon nanoparticles (CNP) (94.4% for unilateral detection and 66.7% for bilateral detection). The upper paracervical pathway (UPP) was detected in 93.3% of cases in the high-risk group and 96.0% of cases in the low-risk group (p = 0.261). The lower paracervical pathway (LPP) was detected in 10.0% of cases in the high-risk group and 17.9% of cases in the low-risk group (p = 0.048). Remarkably increased detection rates of SLN in the common iliac (7.5%) and para-aortic or precaval areas (2.9%) were observed in the high-risk group. In contrast, a markedly decreased detection rate of SLN in the internal iliac area (1.9%) was observed in the high-risk group. CONCLUSION: The highest detection rate of SLN was observed in the subgroup with a combined use of ICG and CNP. The detection of UPP is important for both high-risk and low-risk cases, while LPP detection plays a more important role in the low-risk group. Lymphadenectomy in the common iliac and para-aortic or precaval areas is essential for patients with high-risk EC. Removal of internal iliac lymph nodes is essential for patients with low-risk EC, in case of ineffective SLN mapping.

Recurrent Implantation Failure: Bioinformatic Discovery of Biomarkers and Identification of Metabolic Subtypes.

Recurrent implantation failure (RIF) is a challenging scenario from different standpoints. This study aimed to investigate its correlation with the endometrial metabolic characteristics. Transcriptomics data of 70 RIF and 99 normal endometrium tissues were retrieved from the Gene Expression Omnibus database. Common differentially expressed metabolism-related genes were extracted and various enrichment analyses were applied. Then, RIF was classified using a consensus clustering approach. Three machine learning methods were employed for screening key genes, and they were validated through the RT-qPCR experiment in the endometrium of 10 RIF and 10 healthy individuals. Receiver operator characteristic (ROC) curves were generated and validated by 20 RIF and 20 healthy individuals from Peking University People's Hospital. We uncovered 109 RIF-related metabolic genes and proposed a novel two-subtype RIF classification according to their metabolic features. Eight characteristic genes (SRD5A1, POLR3E, PPA2, PAPSS1, PRUNE, CA12, PDE6D, and RBKS) were identified, and the area under curve (AUC) was 0.902 and the external validated AUC was 0.867. Higher immune cell infiltration levels were found in RIF patients and a metabolism-related regulatory network was constructed. Our work has explored the metabolic and immune characteristics of RIF, which paves a new road to future investigation of the related pathogenic mechanisms.

Metabolic syndrome is an independent risk factor for time to complete remission of fertility-sparing treatment in atypical endometrial hyperplasia and early endometrial carcinoma patients.

OBJECTIVE: Fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients has recently emerged important social health topic. This study is designed to explore the risk factors for time to complete remission (CR) of fertility-sparing treatment in woman with AEH and early EC. METHODS: A retrospective study was designed with clinical data from 106 patients admitted between January 2012 to December 2019. Univariate and multivariate logistic analysis were used to explore independent risk factors for time to CR. These factors were employed in receiver operator characteristic (ROC) curve and the decision curve analysis (DCA) to evaluate predictive accuracy of time to CR. Stratified analysis and interactive analysis was also performed for more in-depth perspective. RESULTS: Univariate analysis showed that fasting blood glucose levels (FBG, OR = 1.6, 95%CI: 0.6-2.5, P = 0.020), metabolic syndrome (MetS, OR = 3.0, 95%CI: 1.1-5.0, P = 0.003), and polycystic ovary syndrome (PCOS, OR = 2.0, 95%CI: 0.5-3.4, P = 0.009) were associated with time to CR. Among these factors, multivariate analysis confirmed MetS (OR = 3.1, 95%CI: 1.0-5.2, P = 0.005) was an independent risk factor. The area under the ROC curve (AUC) of MetS was higher than FBG and PCOS (AUC = 0.723 vs 0.612 and 0.692). The AUC of FBG combined with PCOS was 0.779, and it was improved to 0.840 when MetS was included (P < 0.05). Additionally, MetS played different roles in time to CR in various groups. Moreover, we found high-density lipoprotein (HDL) and MetS had an interactive effect for time to CR. CONCLUSION: MetS is an independent risk factor for time to CR and should be taken seriously in fertility-sparing management of AEH and early EC patients.

Acceleration of pelvic tissue generation by overexpression of basic fibroblast growth factor in stem cells.

BACKGROUND: Pelvic organ prolapse (POP) is a common debilitating condition affecting approximately 30-40% of women. The FDA issued a warning about polypropylene mesh used for pelvic floor repair due to erosion, exposure and other complications and banned it in 2019. The application of stem cell therapy and growth factors has strongly promoted the development of pelvic tissue engineering. PURPOSE: we intend to address the issues of direct application of growth factors, the side effects of long-term exogenous treatment, and the directional differentiation of stem cells. Methods: we evaluated the paracrine effects and directional differentiation of adipose mesenchymal stem cells through stable overexpression of basic fibroblast growth factor (bFGF). RESULTS: we found that the modified stem cells could continuously and stably release bFGF in the initial stage and could spontaneously differentiate into fibroblasts with a high differentiation efficiency in the later stage. CONCLUSION: following ADSCs are designed to continuously release controllable levels of growth factors during the control period of repair, taking advantage of the paracrine function of stem cells to accelerate cell growth and extracellular matrix (ECM) reconstruction during the early stage of stem cell implantation, and then stem cells are differentiated into target tissues-fibroblasts to accelerate the reconstruction of pelvic floor tissues, this study demonstrated the strong therapeutic potential of this approach for pelvic tissue engineering. ABBREVIATIONS: POP: Pelvic organ prolapse; ADSCs: Adipose-derived stem cells; bFGF: Basic fibroblast growth factor; BMSCs: Bone marrow-derived mesenchymal stem cells; HUVECs: Human umbilical vein endothelial cells; EMSCs: Endometrial mesenchymal stem cells; VEGF: Vascular endothelial growth factor; PDGF: Platelet-derived growth factor ECM: Extracellular matrix; IGF: Insulin-like growth factor; HGF: Hepatocyte growth factor; EGF: Epidermal growth factor; BMP-2: Bone morphogenetic protein 2; FBR: Foreign body reaction.

Assessment of prognostic and reproductive outcomes of omentectomy for patients with clinically apparent early-stage (I, II) malignant ovarian germ cell tumours: A multicentre retrospective study.

OBJECTIVE: This study assessed the effect of omentectomy on the prognosis and fertility in patients with clinically early-stage (I, II) malignant ovarian germ cell tumours (MOGCT). DESIGN: A retrospective multicentre study. SETTING: Four university teaching hospitals in China. POPULATION: A total of 268 patients with clinically apparent early-stage (I, II) MOGCT. METHODS: Data were obtained from the medical records. Additionally, the propensity score matching (PSM) algorithm was adopted. MAIN OUTCOME MEASURES: Prognostic outcomes were disease-free survival (DFS) and overall survival (OS). Fertility outcomes were pregnancy and live birth rates. RESULTS: A total of 187 (69.8%) patients underwent omentectomy. Kaplan-Meier analysis showed no significant differences in DFS and OS between the omentectomy and non-omentectomy groups before and after PSM (p > 0.05). Additionally, subgroup analysis stratified by age (<18 and ≥18 years) showed similar results. International Federation of Gynecology and Obstetrics (FIGO) stage was the only risk factor associated with DFS (hazard ratio [HR] 14.71, 95% confidence interval [CI] 4.47-48.38, p < 0.001) and OS (HR 37.36, 95% CI 3.87-361.16, p = 0.002). Pregnancy and live birth rates in the total population were 80.3% and 66.7%, respectively. There were no significant differences between the two groups before and after PSM. CONCLUSIONS: Omentectomy did not improve survival or affect fertility in patients with clinically apparent early-stage (I, II) MOGCT, regardless of the age. The clinical FIGO stage was an independent risk factor for recurrence and death.

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.