Speculation on optimal numbers of examined lymph node for early-stage epithelial ovarian cancer from the perspective of stage migration.

Introduction: In early-stage epithelial ovarian cancer (EOC), how to perform lymphadenectomy to avoid stage migration and achieve reliable targeted excision has not been explored in depth. This study comprehensively considered the stage migration and survival to determine appropriate numbers of examined lymph node (ELN) for early-stage EOC and high-grade serous ovarian cancer (HGSOC). Methods: From the Surveillance, Epidemiology, and End Results database, we obtained 10372 EOC cases with stage T1M0 and ELN ≥ 2, including 2849 HGSOC cases. Generalized linear models with multivariable adjustment were used to analyze associations between ELN numbers and lymph node stage migration, survival and positive lymph node (PLN). LOESS regression characterized dynamic trends of above associations followed by Chow test to determine structural breakpoints of ELN numbers. Survival curves were plotted using Kaplan-Meier method. Results: More ELNs were associated with more node-positive diseases, more PLNs and better prognosis. ELN structural breakpoints were different in subgroups of early-stage EOC, which for node stage migration or PLN were more than those for improving outcomes. The meaning of ELN structural breakpoint varied with its location and the morphology of LOESS curve. To avoid stage migration, the optimal ELN for early-stage EOC was 29 and the minimal ELN for HGSOC was 24. For better survival, appropriate ELN number were 13 and 8 respectively. More ELNs explained better prognosis only at a certain range. Discussion: Neither too many nor too few numbers of ELN were ideal for early-stage EOC and HGSOC. Excision with appropriate numbers of lymph node draining the affected ovary may be more reasonable than traditional sentinel lymph node resection and systematic lymphadenectomy.

Inhibit ALDH3A2 reduce ovarian cancer cells survival via elevating ferroptosis sensitivity.

Ovarian cancer (OC) is a malignant gynecologic tumor with high morbidity and mortality. As a newly discovered mode of programmed cell death, ferroptosis has been involved in various pathological processes of kinds of tumors in recent years. Aldehyde dehydrogenase 3 family member A2 (ALDH3A2) catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid. ALDH3A2 has been shown to be associated with ferroptosis in acute myeloid leukemia (AML), but the mechanism remains unclear. In this study, we analyzed the TCGA and GTEx databases and showed that high ALDH3A2 expression predicted poor prognosis in ovarian cancer. Further studies found that knockout or overexpression of ALDH3A2 correspondingly increased or attenuated the ferroptosis sensitivity of ovarian cancer cells. And sequencing revealed that ALDH3A2 knockout led to the activation of lipid metabolic, GSH metabolic, phospholipid metabolic, and aldehyde metabolic pathways, suggesting that ALDH3A2 induced changes in the sensitivity of ovarian cancer cells to ferroptosis by affecting these metabolic processes. Our results provide a new promising therapeutic strategy for the treatment of OC.

UQCRFS1 serves as a prognostic biomarker and promotes the progression of ovarian cancer.

UQCRFS1 has been reported to be highly expressed in gastric and breast cancer, but the mechanism remains unclear. The prognosis and biological functions of UQCRFS1 in ovarian cancer (OC) have not been evaluated. The expression of UQCRFS1 in EOC was detected by GEPIA and HPA websites, and the prognosis value was investigated by Kaplan-Meier analysis. Then the correlation between the UQCRFS1 gene and tumor-related signature were analyzed by Spearman correlation analysis and rank sum test. Subsequently, the expression of the UQCRFS1 gene in four ovarian cancer cell lines was detected. A2780 and OVCAR8 with the highest expression of UQCRFS1 were selected in the following biological experiments. Cell proliferation was detected by CCK8 assay, cell cycle and apoptosis were determined by flow cytometry, reactive oxygen species (ROS) production was detected by DCFH-DA, DNA damage gene mRNA expression was analyzed by RT-PCR, and AKT/mTOR pathway protein expression were also examined by western blot after siRNA transfection. We found that UQCRFS1 was high-expression in EOC and associated with poor prognosis. Spearman correlation analysis revealed that the high expression of UQCRFS1 is associated with the cell cycle, apoptosis, oxidative phosphorylation, and DNA damage. Further studies found that knockdown of UQCRFS1 cells reduced cell proliferation, cell cycle arrest at the G1 phase, increased proportion of apoptosis, ROS production, and expression of DNA damage genes, inhibited ATK/mTOR pathway. The study suggested that UQCRFS1 may be a candidated target for diagnosis and treatments in OC.

Tumor microenvironment manipulates chemoresistance in ovarian cancer (Review).

Ovarian cancer (OC) is the leading cause of mortality among the various types of gynecological cancer, and >75% of the cases are diagnosed at a late stage. Although platinum­based chemotherapy is able to help the majority of patients to achieve remission, the disease frequently recurs and acquires chemoresistance, resulting in high mortality rates. The complexity of OC therapy is not solely governed by the intrinsic characteristics of the OC cells (OCCs) themselves, but is also largely dependent on the dynamic communication between OCCs and various components of their surrounding microenvironment. The present review attempts to describe the mutual interplay between OCCs and their surrounding microenvironment. Tumor­associated macrophages (TAMs) and cancer­associated fibroblasts (CAFs) are the most abundant stromal cell types in OC. Soluble factors derived from CAFs steadily nourish both the OCCs and TAMs, facilitating their proliferation and immune evasion. ATP binding cassette transporters facilitate the extrusion of cytotoxic molecules, eventually promoting cell survival and multidrug resistance. Extracellular vesicles fulfill their role as genetic exchange vectors, transferring cargo from the donor cells to the recipient cells and propagating oncogenic signaling. A greater understanding of the vital roles of the tumor microenvironment will allow researchers to be open to the prospect of developing therapeutic approaches for combating OC chemoresistance.

The effect of preperitoneal pelvic packing for hemodynamically unstable patients with pelvic fractures.

PURPOSE: Hemodynamically unstable patients with pelvic fractures still represent a challenge to trauma surgeons and have a very high mortality. This study was designed to explore the effect of the interventions of direct preperitoneal pelvic packing for the hemodynamically unstable pelvic fractures. METHODS: This retrospective study enrolled 67 cases of severe pelvic fractures with unstable hemodynamics from October 2011 to December 2019. All patients presented in our emergency center and received preperitoneal pelvic packing were included in this study. The indication was persistent systolic blood pressure ≤90 mmHg during initial resuscitation and after transfusion of two units of red blood cells. Patients with hemodynamic stability who need no preperitoneal pelvic packing to control bleeding were excluded. Their demographic characteristics, clinical features, laboratory results, therapeutic interventions, adverse events, and prognostic outcomes were collected from digital information system of electronic medical records. Statistics were described as mean ± standard deviation or medium and analyzed using pair sample t-test or Mann-Whitney U-test. RESULTS: The patients' average age was 41.6 years, ranging from 10 to 88 years. Among them, 45 cases were male (67.2%) and 22 cases were female (32.8%). Significant difference was found regarding the systolic blood pressure (mmHg) in the emergency department (78.4 ± 13.9) and after preperitoneal pelvic packing in the surgery intensive care unit (100.1 ± 17.6) (p < 0.05). Simultaneously, the arterial base deficit (mmol/L) were significantly lower in the surgery intensive care unit (median -6, interquartile range -8 to -2) than in the emergency department (median -10, interquartile range -14 to -8) (p < 0.05). After preperitoneal pelvic packing, 15 patients (22.4%) underwent pelvic angiography for persistent hypotension or suspected ongoing haemorrhage. The overall mortality rate was 29.5% (20 of 67). CONCLUSIONS: Preperitoneal pelvic packing, as a useful surgical technique, is less invasive and can be very efficient in early intra-pelvic bleed control.

Construction of a new tumor immunity-related signature to assess and classify the prognostic risk of ovarian cancer.

Ovarian cancer is associated with a high mortality rate. In this study, we established a new immune-related signature that can stratify ovarian cancer patients. First, we obtained immune-related genes through IMMUPORT, and DEGs (Differential Expression Genes) by analyzing the GSE26712 dataset. The APP (Antigen Processing and Presentation) and DEG signatures were established using univariate and multivariate Cox models. Kaplan-Meier analysis revealed the signatures' prognostic value in training and validation cohorts (HR: 0.379 VS. 0.450; 0.333 VS. 0.327). Nomogram analysis was used to assess the signatures' ability to predict the 30-month prognosis, which was evaluated using the calibration curve and time-dependent ROC curve (30-month AUC: 0.665 VS. 0.743). Time-dependent ROC, Decision Curve Analysis (DCA) and Integrated discrimination improvement (IDI) was used to compare the new model to previously published gene signatures. 30-month AUC composite variable (0.736) was higher than 9-gene signature (0.657), and composite variable had a larger net benefit and a higher IDI (+2.436%) relative to the 9-gene signature. Tumor immune infiltration and tumor microenvironment scores of the 2 groups separated by APP signature were compared. GSEA was used to identify enriched KEGG pathways. Conclusively, the proposed signature can stratify ovarian cancer patients by risk-score and guide clinical decisions.

A Retrospective Analysis of the Treatment of Cesarean Scar Pregnancy by High-Intensity Focused Ultrasound, Uterine Artery Embolization and Surgery.

Objective: This study aims to retrospectively analyze the clinical curative effects of surgery, uterine artery embolization (UAE), and high-intensity focused ultrasound (HIFU) in order to provide the theory and evidences for selecting the optimal treatment for cesarean scar pregnancy (CSP). Methods: Women with CSP were treated with surgery (laparoscopic, hysteroscopy, and hysteroscopy-laparoscopic surgery), UAE combined with curettage, and HIFU combined with curettage. The general conditions and therapeutic effects, including vital signs during the operation, discomfort of discharge, cure rate, total blood loss, decline in the rate of hCG, and hospital stay, were compared and analyzed. Results: For the 154 CSP patients, the cure rate of surgery (n = 95) was 97.89%, the cure rate of UAE (n = 32) was 43.74%, and the cure rate of HIFU (n = 27) was 70.37%. The difference was statistically significant (P < 0.05). Furthermore, the hCG level of surgical patients quickly declined, whereas HIFU slowly declined. The difference between the decline rate of hCG and mean hospitalization time was statistically significant (P < 0.05). UAE was good for CSP with gestational age <60 days and diameter of gestational sac <40 mm. Furthermore, HIFU was well for CSP patients with a gestational age of <55 days and a gestational sac diameter of <30 mm. Surgery was suitable for any type of these cases. Conclusion: CSP patients with short gestational age and small gestational sac can be treated with surgery, UAE, and HIFU, and achieve safe and effective therapeutic effects. Surgery is also a good choice for CSP for patients with a long gestational age, a large gestational sac diameter, high levels of hCG, or an ample blood supply.

IDRiD: Diabetic Retinopathy - Segmentation and Grading Challenge.

Diabetic Retinopathy (DR) is the most common cause of avoidable vision loss, predominantly affecting the working-age population across the globe. Screening for DR, coupled with timely consultation and treatment, is a globally trusted policy to avoid vision loss. However, implementation of DR screening programs is challenging due to the scarcity of medical professionals able to screen a growing global diabetic population at risk for DR. Computer-aided disease diagnosis in retinal image analysis could provide a sustainable approach for such large-scale screening effort. The recent scientific advances in computing capacity and machine learning approaches provide an avenue for biomedical scientists to reach this goal. Aiming to advance the state-of-the-art in automatic DR diagnosis, a grand challenge on "Diabetic Retinopathy - Segmentation and Grading" was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI - 2018). In this paper, we report the set-up and results of this challenge that is primarily based on Indian Diabetic Retinopathy Image Dataset (IDRiD). There were three principal sub-challenges: lesion segmentation, disease severity grading, and localization of retinal landmarks and segmentation. These multiple tasks in this challenge allow to test the generalizability of algorithms, and this is what makes it different from existing ones. It received a positive response from the scientific community with 148 submissions from 495 registrations effectively entered in this challenge. This paper outlines the challenge, its organization, the dataset used, evaluation methods and results of top-performing participating solutions. The top-performing approaches utilized a blend of clinical information, data augmentation, and an ensemble of models. These findings have the potential to enable new developments in retinal image analysis and image-based DR screening in particular.

IP10-CDR3 Reduces The Viability And Induces The Apoptosis Of Ovarian Cancer Cells By Down-Regulating The Expression Of Bcl-2 And Caspase 3.

PURPOSE: This study aimed to explore the effects of interferon-γ inducible protein 10 (IP10) and complementarity-determining region 3 (CDR3) of T cells receptor on ovarian cancer cells and the involved mechanisms. METHODS: IP10 and CDR3 were linked with single-chain antibody (scfv) and exotoxin gene muton of Pseudomonas aeruginosa (PE40) to construct IP10-CDR3scfv and IP10-CDR3-PE40scfv. Then, we constructed pcDNA3.1-IP10-CDR3scfv and pcDNA3.1-IP10-CDR3-PE40scfv plasmids which were proved by HindIII/EcoRI digestion. SKOV3 cells and HOSEpiC cells were incubated with fluorescein isothiocyanate (FITC) labeled IP10-CDR3scfv and IP10-CDR3-PE40scfv proteins and protein levels were examined by flow cytometry. After gene transfection, SKOV3 cells were divided into four groups: Control, pcDNA3.1(+) negative control (NC) (pcDNA3.1(+) NC transfection), IP10-CDR3scfv (IP10-CDR3scfv transfection) and IP10-CDR3-PE40scfv (IP10-CDR3-PE40scfv transfection). Levels of IP10, CDR3, Caspase-3, cleaved Caspase-3 and Bcl-2 were determined by RT-PCR and Western blot. Cell viability and apoptosis were investigated by CCK-8 assay and Annexin V-FITC/PI assay, respectively. RESULTS: The levels of FITC-labeled IP10-CDR3scfv and IP10-CDR3-PE40scfv proteins in the SKOV3+IP10-CDR3scfv group and the SKOV3+IP10-CDR3-PE40scfv group were remarkably higher than that in the SKOV3 group (P<0.05). So was the HOSEpiC related groups. There was no obvious difference in the levels of IP10, CDR3, Caspase-3, cleaved Caspase-3 and Bcl-2 between the control group and the pcDNA3.1(+) NC group. However, compared with the control group, the levels of Caspase-3 and Bcl-2 were reduced notably and the levels of IP10, CDR3 and cleaved Caspase-3 were elevated sharply in the IP10-CDR3scfv and IP10-CDR3-PE40scfv groups (P<0.05). The control group and the pcDNA3.1(+) NC group demonstrated similar cell viability and apoptosis. However, compared with the control group, cell viability in the IP10-CDR3scfv and IP10-CDR3-PE40scfv groups decreased significantly and cell apoptosis increased (P<0.05). CONCLUSION: IP10-CDR3 could reduce the viability and induce the apoptosis of ovarian cancer cells by down-regulating the expression of Bcl-2 and Caspase-3.

Assessment of Parametrial Involvement in Early Stages Cervical Cancer With Preoperative Magnetic Resonance Imaging.

OBJECTIVE: The objective of this study was to develop a predictive model for parametrial involvement (PMI) and to identify low-risk group of PMI in early stages of cervical cancer based on preoperative magnetic resonance imaging (MRI) parameters. METHODS: We retrospectively analyzed patients with stages IB1 to IIA2 cervical cancer (N = 1347) who underwent type C radical hysterectomy between 2005 and 2012. Clinical records, preoperative MRI, and its association with pathological data were reviewed. A predictive model for PMI was developed using preoperative MRI parameters for the estimation of its performance. RESULTS: Of 1347 patients, 138 (10.2%) had pathological PMI (p-PMI). Multivariate analysis identified the maximal tumor diameter (odds ratio, 2.0; 95% confidence interval, 1.23-3.40; P < 0.001) and PMI (odds ratio, 7.0; 95% confidence interval, 4.49-11.02; P < 0.001) on preoperative MRI (m-PMI) as independent predictive factors for p-PMI. The rate of p-PMI was 1.3% for low-risk patients identified by the current model (maximal tumor diameter ≤2.5 cm and no indication of PMI, n = 448). The 5-year progression-free survival rate was significantly greater (96.7%) in low-risk patients than in those with a maximal tumor diameter greater than 2.5 cm and/or indication of m-PMI (90.8%, P = 0.004). CONCLUSIONS: A predictive model for p-PMI was developed in which p-PMI exclusion was set as a maximal tumor diameter less than or equal to 2.5 cm and no indication of m-PMI. Patients with a low risk of m-PMI could be identified so that less radical surgery for stages IB1 to IIA2 cervical cancer could be offered.

Expression of serum human epididymal secretory protein E4 at low grade and high grade serous carcinomas.

OBJECTIVE: To investigate the value of serum human epididymis protein 4 (HE4) in differential diagnosis of patients with low-grade serous (LGSC) and high-grade serous carcinoma (HGSC) serous ovarian cancer. METHODS: LGSC and HGSC serous ovarian cancer were diagnosed by the two-tier grade system, serum levels of HE4 and carbohydrate antigen 125 (CA125) were measured by ELISA and radioisotope method, respectively in 60 serous ovarian cancer patients. HE4 and TP53 protein in cancer tissue were measured by immunohistochemical method. RESULTS: The difference in density of HE4 and TP53 protein was significant between LGSC and HGSC tissue, while serum CA125 did not show significant difference between different serum samples. There was significant difference in serum HE4 levels between LGSC and HGSC, and the result was different within FIGO (I+II) stage, suggesting HE4 was not a reliable biomarker for the discrimination between LGSC and HGSC. HE4 had potential as a biomarker for the discrimination between LGSC and HGSC but the role in early diagnosis was limited. CONCLUSIONS: HE4 may be a reliable marker for differential diagnosis of LGSC and HGSC. But its role in early diagnosis of LGSC and HGSC need to be confirmed from the perspective of two-tier grade system.

Inside out transobturator vaginal tape versus tention-free vaginal tape for primary female stress urinary incontinence: meta-analysis of randomized controlled trials.

BACKGROUND: Inside out transobturator vaginal tape (TVT-O) and tension-free vaginal tape (TVT) are predominant surgical treatments for female stress urinary incontinence. This meta-analysis evaluated the complications and cure rates of TVT-O versus TVT. METHODS: A comprehensive literature search was conducted according to the Cochrane Collaboration methodology to identify randomized controlled clinical trials with no language restriction. Two authors independently assessed papers for eligibility and methodological quality. Estimates were measured by relative risk with 95% confidence intervals. Outcome measures were objective cure, subjective cure and complications. Quality rating for each outcome of the meta-analysis and recommendations were performed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Twenty randomized controlled trials met the inclusion criteria, and a pooled estimate of effectiveness and complications was made. Relative risks with 95% confidence intervals for pooled effects under the fixed effects model were: 0.20 (0.09 - 0.45), for bladder injury, 0.37 (0.16 - 0.86) for hematoma, and 2.35 (1.57 - 3.51) for postoperative pain, suggesting an 80% risk reduction of bladder injury, 63% risk reduction of hematoma, and a 1.35% risk elevation for postoperative pain with TVT-O. There was no significant difference between complications of urinary tract infection 1.14 (0.78 - 1.65), lower urinary tract symptoms 1.60 (0.67 - 3.79), recatheterization 0.93 (0.59 - 1.44), and tape erosion 0.90 (0.48 - 1.67), total objective cure rate 1.06 (0.39 - 2.84) and for the subjective cure rate 0.98 (0.93 - 1.04). The quality rating for each outcome and recommendations was high for objective cure, bladder injury, hematoma, lower urinary tract symptoms, and tape erosion and moderate for subjective cure, pain, and urinary tract infection. CONCLUSIONS: TVT-O is associated with a reduced risk of bladder injury and hematoma and an elevated risk of postoperative pain. Other complications, including tape erosion, urinary tract infection, lower urinary tract symptoms, and recatheterization, are similar to those of TVT.