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We investigated the potential diagnostic and prognostic role of maternally expressed 3 (MEG-3), a type of long non-coding RNA, in epithelial ovarian carcinoma (EOC) by comparing long non-coding RNA (LNCRNA-MEG-3) expression in EOC and normal ovarian tissues and exploring clinical correlations. The study included 126 patients diagnosed with stage III EOC, confirmed by histopathological examination. We used quantitative polymerase chain reaction (qPCR) to quantify levels of the long noncoding RNA MEG-3. The long non-coding RNA MEG-3 expression in EOC tissues was significantly lower than in normal ovarian tissues, indicating its potential as a diagnostic marker. Receiver operating characteristic curve (ROC) analysis demonstrated an Area under the ROC Curve (AUC) of 0.831, signifying its high sensitivity (100%) and specificity (97.04%) in distinguishing malignant ovarian tissues from normal ones. LNCRNA-MEG-3 expression varied significantly across different EOC stages (p < 0.0001) and tumor grades (p < 0.0001), correlating with aggressive behavior and serous tumor types. Low LNCRNA-MEG-3 expression associated with adverse prognostic factors such as ascites (p < 0.0001) and poor treatment response (p < 0.0001). High LNCRNA-MEG-3 expression predicted better treatment response. It also correlates with the size of residual disease after debulking surgery, which is an important prognostic factor. Compared to those with low LNCRNA-MEG-3 expression, patients with high expression had significantly longer overall and disease-free survival (p = 0.0004 and p = 0.0002, respectively). The study highlights LNCRNA-MEG-3 as a valuable diagnostic and prognostic marker for EOC. Low expression of the long non-coding RNA MEG-3 is linked to aggressive tumor features and unfavorable clinical outcomes, stressing the importance of MEG-3 in managing EOC and tailoring the treatment to the individual patient. [ABSTRACT FROM AUTHOR]

Ovarian cancer is classified as a gynaecological cancer, but the symptoms present as abdominal and they can be mistaken for those of a bowel condition or bladder problems. Target Ovarian Cancer is urging clinicians to recognise the red flags for ovarian cancer, and to never diagnose new-onset irritable bowel syndrome (IBS) or overactive bladder in women over 50 without ruling out ovarian cancer. The symptoms of these are also red flags for ovarian cancer and warrant further investigations. This article covers how to spot these red flags, safety netting and what to do if you suspect a woman's symptoms may be ovarian cancer. [ABSTRACT FROM AUTHOR]

Intraoperative consultation (IC) is often used for surgical planning in gynecological oncology, primarily in ovarian and endometrial cancer surgery. However, there is limited research that compares IC diagnoses and results from definitive analyses. This retrospective study compares IC results and definitive analysis findings in terms of ovarian mass diagnoses and endometrial carcinoma patients consulted for myometrial invasion (MI) depth across 7 years (2012-2019). IC was performed in 282 cases to evaluate ovarian masses. The sensitivity of IC was 94% for benign ovarian masses and 90% for malignant ovarian masses. 92 cases were submitted to IC for endometrial carcinoma. Sensitivity was 80% for tumors with <50% MI and 74% for tumors with ≥50% MI. IC is an important method with high sensitivity and specificity for diagnosing ovarian masses and determining MI depth in endometrial carcinomas. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is often diagnosed in its advanced stages with many patients suffering from recurrence. Relapse is frequent after standard treatment leading to platinum resistance and poor prognosis in patients. Several studies have reported that immune status and inflammatory factors, such as Interleukin-17D (IL-17D), are major players in the prognosis of malignant tumors. IL-17 family is an important pro-inflammatory cytokine family, which mediates immunosuppression and promotes tumor progression. Our previous exploration revealed the promoting role of IL-17D expression in the occurrence and development of ovarian carcinoma, but the specific mechanism remains unclear. In this study, we investigated the effects of rhIL-17D on the proliferation, migration and invasion of human ovarian carcinoma cell SKOV3 in vitro. In addition, we also detected the effect of rhIL-17D on programmed death ligand- 1 (PD-L1) expression of SKOV3 cells and possible mechanism.We found that rhIL- 17D accelerated SKOV3 cell proliferation rate, enhanced the migration and penetration ability, and promoted the expression of PD-L1. After knockdown P65 expression,the activated form of NF-κB, in SKOV3 cells, the proliferation activity, migration, and invasion of ovarian cancer cells were significantly reduced. And the expression of PDL1 decreased. In summary, we believe that IL-17D can accelerate cell proliferation and enhance cell migration and invasion abilities of ovarian cancer and induce PD-L1 expression by regulating the activation of NF-κB pathway. Down-regulation of IL-17D in tumor microenvironment may be a new approach to inhibit ovarian cancer. [ABSTRACT FROM AUTHOR]

Objectives: To assess the role of the positron emission tomography with fluorine-18-deoxyglucose (PET/CT) in the detection of recurrent serous ovarian cancer in patients with normal serum CA125 level. Material and methods: Thirty-one patients with suspected recurrent serous ovarian cancer with normal (< 35 IU/mL) serum CA125 level and no prior recurrence underwent PET/CT imaging. The results of the PET/CT were analyzed considering clinical data of the patients, histological diagnosis and 6 months follow-up. Results: The patients were referred to the PET/CT due to suspected relapse in imaging tests (CT -- 11 cases, US -- 3 cases, MRI -- 2 cases; n = 16; 51.6%), clinical examination (n = 4; 12.9%) and clinical symptoms (n = 11; 35.5%). The recurrent serous ovarian cancer was present in 16 patients (51.6%). In 9 these cases (56.3%) the recurrences were diagnosed in patients aged 51-70 years. In 15 cases (93.8%) the recurrences were diagnosed within 24 months after treatment. There were 15 true positive (48.4%), 12 true negative (38.7%), 3 false positive (9.7%) and 1 false negative (3.2%) PET//CT results. Sensitivity, specificity, positive and negative predictive value of the PET/CT were calculated as 93.8% (95% CI, 86.1-97.4%), 80.0% (95% CI, 69.7-88.9%), 83.3% (95% CI, 74.3-90.4%) and 92.3% (95% CI, 84.2-98.3%), respectively. Conclusions: In patients with a diagnosis of complete remission after treatment for serous ovarian cancer, even a multifocal recurrence may occur during follow up despite normal serum CA125 levels. Our results showed a usefulness of the PET/CT in detecting and differentiating malignant from benign lesions in patients with normal serum CA125 levels but inconclusive results in other imaging tests. We observed false results of the PET/CT for lesions in parotid gland, mesorectal adipose tissue and mediastinal lymph nodes. [ABSTRACT FROM AUTHOR]

Introducing PARP inhibitors maintenance therapy into clinical practice significantly improved treatment outcomes in patients with high-grade platinum-sensitive advanced ovarian cancer, the most lethal gynecological malignancy. Niraparib is a potent PARP inhibitor whose safety and efficacy were assessed in the placebo-controlled, randomized clinical trial PRIMA. Niraparib significantly prolonged progression-free survival in the overall population of high-grade advanced ovarian cancer regardless of BRCA1 and BRCA2 mutation and homologous deficiency status compared to placebo. However, the most significant benefit was observed in BRCA mutated and homologous recombination deficient subgroups. Niraparib has a manageable toxicity profile and is well-tolerated by patients. Most common toxicities are hematological and can be managed with drug interruption and/or dose reduction that do not decrease efficacy. Niraparib is recommended for patients who responded to the first-line chemotherapy with platinum compound regardless of homologous recombination status. This review will discuss the use of niraparib in newly diagnosed advanced ovarian cancer patients focusing on its efficacy and tolerability. Additionally, a case series will be presented to further discuss this drug use in clinical practice in Poland. [ABSTRACT FROM AUTHOR]

Noble metal nanostructured substrates enhance photoluminescence emitted from molecules immobilized onto their surface, allowing for the development of highly sensitive immunoassays employing fluorescent labels. In this work, nanostructured silver surfaces were implemented as substrates for the immunochemical detection of two ovarian cancer markers, carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4). Biotinylated detection antibodies were used to allow for the detection of immunocomplexes through a reaction with streptavidin conjugated to Rhodamine Red-X. The detection limits achieved were 2.5 U/mL and 0.06 ng/mL for CA125 and HE4, respectively, with linear dynamic ranges, covering the concentration ranges of both healthy and ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Precise radiological evaluation is pivotal for the management of platinum-sensitive recurrent ovarian cancer. We aimed to compare the value of [68 Ga]-FAPI and [18F]-FDG PET/CT for the detection of relapsed lesions. Methods: Twenty-nine suspected platinum-sensitive recurrent ovarian cancers were enrolled from January 2022 to July 2022. [18F]-FDG and [68 Ga]-FAPI PET/CT were obtained within 1 week for radiological evaluation. Treatment strategies, visual scores, and Eisenkop scores were recorded. A paired T test was used to compare differences between two scans. Sensitivity, specificity, PPV, NPV, and accuracy were also evaluated. Results: Up to 22 (75.86%) patients displayed inconsistency between two scans. Among them, 4 patients with negative [18F]-FDG imaging had measurable lesions in [68 Ga]-FAPI scans. The treatment strategies were changed in 5 patients (17.24%) due to discrepancies. Finally, 15 (35.7%) patients underwent surgeries, and 14 patients achieved complete resection, except for 1 patient who had milliarc residual disease. TBR, but not SUVmax, of [68 Ga]-FAPI was significantly higher than that of [18F]-FDG in recurrent lesions. Compared with [18F]-FDG, [68 Ga]-FAPI PET presented higher sensitivity and accuracy for lesion detection (96.30% vs. 49.07% and 97.40% vs. 63.87%, respectively). Additionally, [68 Ga]-FAPI PET showed a much higher visual score than [18F]-FDG PET (41 vs. 4), especially for peritoneal metastasis (35 vs. 1). [68 Ga]-FAPI PET also presented a larger tumor burden than [18F]-FDG according to the Eisenkop score (27 vs. 16, p = 0.025). Conclusions: [68 Ga]-FAPI was superior to [18F]-FDG PET/CT for the detection of recurrent lesions, which is pivotal for the individualized management of platinum-sensitive recurrent ovarian cancer. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate an MRI-based radiomics nomogram for the preoperative prediction of miliary changes in the small bowel mesentery (MCSBM) in advanced high-grade serous ovarian cancer (HGSOC). Materials and methods: One hundred and twenty-eight patients with pathologically proved advanced HGSOC (training cohort: n = 91; validation cohort: n = 37) were retrospectively included. All patients were initially evaluated as MCSBM-negative by preoperative imaging modalities but were finally confirmed by surgery and histopathology (MCSBM-positive: n = 53; MCSBM-negative: n = 75). Five radiomics signatures were built based on the features from multisequence magnetic resonance images. Independent clinicoradiological factors and radiomics-fusion signature were further integrated to construct a radiomics nomogram. The performance of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves and clinical utility. Results: Radiomics signatures, ascites, and tumor size were independent predictors of MCSBM. A nomogram integrating radiomics features and clinicoradiological factors demonstrated satisfactory predictive performance with areas under the curves (AUCs) of 0.871 (95% CI 0.801–0.941) and 0.858 (95% CI 0.739–0.976) in the training and validation cohorts, respectively. The net reclassification index (NRI) and integrated discrimination improvement (IDI) revealed that the nomogram had a significantly improved ability compared with the clinical model in the training cohort (NRI = 0.343, p = 0.002; IDI = 0.299, p < 0.001) and validation cohort (NRI = 0.409, p = 0.015; IDI = 0.283, p = 0.001). Conclusion: Our proposed nomogram has the potential to serve as a noninvasive tool for the prediction of MCSBM, which is helpful for the individualized assessment of advanced HGSOC patients. [ABSTRACT FROM AUTHOR]

Peritoneal mesothelioma is a rare neoplasm that is associated with multiple diagnostic and therapeutic challenges. Therapeutic guidelines are scarce and based on extrapolative data. Histopathological diagnosis is difficult as neither the morphological finding nor the immunohistochemical stains are specific. The mainstay treatment for resectable disease is cytoreductive surgery with intraperitoneal chemotherapy being a valuable addition. Treatment of non-resectable cases includes platinum-based chemotherapy, immune checkpoint inhibitors, and bevacizumab. We present a case of a 49-year-old woman suffering from inoperable peritoneal mesothelioma, which was initially diagnosed as ovarian cancer and treated accordingly. [ABSTRACT FROM AUTHOR]

Purpose: To explore values of intra- and peritumoral CT-based radiomics for predicting recurrence in high-grade serous ovarian cancer (HGSOC) patients. Methods: This study enrolled 110 HGSOC patients from our hospital between Aug 2017 and Apr 2021. All patients underwent contrast-enhanced CT scans before treatment. The least absolute shrinkage and selection operator (LASSO) regression was used to select radiomics features from intra- and peritumoral areas. Radiomics signatures were built based on selected features from Intra-RS, Peri-RS, and in Com-RS. A nomogram was constructed by combining radiomics signatures and clinical parameters with predictive potential. Receiver operating characteristics (ROC), calibration, and decision curve analyses (DCA) curves were used to evaluate performance of the nomogram. Results: The intra- and peritumoral combined Com-RS showed effective ability in predicting recurrent HGSOC in the training (AUCs, Intra-RS vs. Peri-RS vs. Com-RS, 0.861 vs. 0.836 vs. 899) and validation (AUCs, Intra-RS vs. Peri-RS vs. Com-RS, 0.788 vs. 0.762 vs. 815) cohort. The Federation of International of FIGO stage, menstruation, and location were found to be strongly associated with tumor recurrence. The nomogram has the best predictive ability in the training (AUCs, Com-RS vs. clinical model vs. nomogram, 0.899 vs. 0.648 vs. 0.901) and validation (AUCs, Com-RS vs. clinical model vs. nomogram, 0.815 vs. 0.666 vs. 0.818) cohort. Conclusion: Our findings suggested values of intra- and peritumoral-based radiomics for predicting recurrent HGSOC. The constructed nomogram may be of importance in clinical application. [ABSTRACT FROM AUTHOR]

Purpose: To determine pathways to endometrial or ovarian cancer diagnosis by comparing health service utilization between cancer cases and matched cancer-free controls, using linked health records. Methods: From cancer registry records, we identified 238 incident endometrial and 167 ovarian cancer cases diagnosed during 2006–2013 in the Australian 45 and Up Study cohort (142,973 female participants). Each case was matched to four cancer-free controls on birthdate, sex, place of residence, smoking status, and body mass index. The use of relevant health services during the 13–18-, 7–12-, 0–6-, and 0–1-months pre-diagnosis for cases and the corresponding dates for their matched controls was determined through linkage with subsidized medical services and hospital records. Results: Healthcare utilization diverged between women with cancer and controls in the 0–6-months, particularly 0–1 months, pre-diagnosis. In the 0–1 months, 74.8% of endometrial and 50.3% of ovarian cases visited a gynecologist/gynecological oncologist, 11.3% and 59.3% had a CA125 test, 5.5% and 48.5% an abdominal pelvic CT scan, and 34.5% and 30.5% a transvaginal pelvic ultrasound, respectively (versus ≤ 1% of matched controls). Moreover, 25.1% of ovarian cancer cases visited an emergency department in the 0–1-months pre-diagnosis (versus 1.3% of matched controls), and GP visits were significantly more common for cases than controls in this period. Conclusion: Most women with endometrial or ovarian cancer accessed recommended specialists and tests in the 0–1-months pre-diagnosis, but a high proportion of women with ovarian cancer visited an emergency department. This reinforces the importance of timely specialist referral. [ABSTRACT FROM AUTHOR]

A robust real-time flow injection assay using Quartz Crystal Microbalance (QCM) biosensor has been developed for the detection of mesothelin, an antigen expressed on various malignant tumors including mesothelioma and ovarian cancers. A QCM sensor chip functionalized with self-assembled monolayer of cysteamine used to fabricate a sensitive immunosensor. Mesothelin specific antibody was immobilized on cysteamine modified gold surface of quartz crystal using N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide and N-hydroxy succinimide coupling. Further, ethanolamine was used as a blocking reagent to prevent the non-specific adsorption on antibody functionalized gold surface. Various concentrations of mesothelin was tested and the resonant frequency variation of the crystal was observed by a quartz crystal microbalance until a stable response is obtained. A good correlation between the frequency changes and concentration of mesothelin tested was observed and the QCM biosensor detects mesothelin in the linear range of 100pg/mLto 50 ng/mL. Thus, QCM assay could be a promising technique for early diagnosis of mesothelioma, ovarian and pancreatic adenocarcinoma. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have recently emerged as effective regulatory agents in biological processes as well as in the formation of tumors. LncRNAs are important regulators of cell transformation and cancer progression. LncRNA NEAT1 is one of the most important lncRNAs, and its deregulation has been reported in a variety of human cancers. Ovarian cancer has an inverse relationship with the number of reported pregnancies and deliveries, while it has a direct relationship with infertility. This study aimed to investigate NEAT1 expression in ovarian cancer. A total of 140 tissue samples, including 70 ovarian tumors and 70 marginal samples, were included in the study. Total RNA was extracted using the RNXplus solution. The quality and quantity of the extracted RNAs were determined using gel electrophoresis and a NanoDrop device. The complementary DNA was synthesized by the reverse transcriptase enzyme, and quantitative reverse transcriptase PCR was used to quantify the expression of NEAT1. A comparison between the mean expression of NEAT1 in ovarian tumors and marginal samples showed an increase in NEAT1 expression in tumor tissue that was not statistically significant (P-value = 0.2). ROC curve analysis also showed that NEAT1 expression level might not be an informative biomarker for ovarian cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: We performed a systematic review and meta-analysis aiming to assess the diagnostic performance of the Ovarian Adnexal Report Data System (O-RADS) using transvaginal ultrasound for classifying adnexal masses. Data from 11 studies comprising 4634 masses showed that the pooled estimated sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of O-RADS system for classifying adnexal masses were 97% (95% confidence interval (CI) = 94%–98%), 77% (95% CI = 68%–84%), 4.2 (95% CI= 2.9–6.0), 0.04 (95% CI = 0.03–0.07), and 96 (95% CI = 50–185), respectively. We concluded that the O-RADS system has good sensitivity and moderate specificity for classifying adnexal masses. In this systematic review and meta-analysis, we aimed to assess the pooled diagnostic performance of the so-called Ovarian Adnexal Report Data System (O-RADS) for classifying adnexal masses using transvaginal ultrasound, a classification system that was introduced in 2020. We performed a search for studies reporting the use of the O-RADS system for classifying adnexal masses from January 2020 to April 2022 in several databases (Medline (PubMed), Google Scholar, Scopus, Cochrane, and Web of Science). We selected prospective and retrospective cohort studies using the O-RADS system for classifying adnexal masses with histologic diagnosis or conservative management demonstrating spontaneous resolution or persistence in cases of benign appearing masses after follow-up scan as the reference standard. We excluded studies not related to the topic under review, studies not addressing O-RADS classification, studies addressing MRI O-RADS classification, letters to the editor, commentaries, narrative reviews, consensus documents, and studies where data were not available for constructing a 2 × 2 table. The pooled sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio (DOR) were calculated. The quality of the studies was evaluated using QUADAS-2. A total of 502 citations were identified. Ultimately, 11 studies comprising 4634 masses were included. The mean prevalence of ovarian malignancy was 32%. The risk of bias was high in eight studies for the "patient selection" domain. The risk of bias was low for the "index test" and "reference test" domains for all studies. Overall, the pooled estimated sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and DOR of the O-RADS system for classifying adnexal masses were 97% (95% confidence interval (CI) = 94%–98%), 77% (95% CI = 68%–84%), 4.2 (95% CI = 2.9–6.0), 0.04 (95% CI = 0.03–0.07), and 96 (95% CI = 50–185), respectively. Heterogeneity was moderate for sensitivity and high for specificity. In conclusion, the O-RADS system has good sensitivity and moderate specificity for classifying adnexal masses. [ABSTRACT FROM AUTHOR]

Background and objectives Epithelial ovarian cancer (OC) is a clinically, morphologically, and molecularly heterogeneous disease. Estrogen receptor (ER) ß is highly represented in normal ovarian epithelial cells and benign tumors, but ERa is the main form expressed in OC. ERa-positive OC had a favorable outcome. Progesterone receptor (PR) expression in ovarian tumors is a good prognostic marker associated with longer progression-free survival. Human epidermal growth-factor receptor (HER) 2 expression is associated with a worse prognosis. The aim of the study was to evaluate immunohistochemical (IHC) expression of ER, PR, and HER2/neu in ovarian epithelial tumors and to correlate their expression with different demographic, clinical, and pathological parameters. Patients and methods Sixty cases of primary ovarian epithelial tumors were studied according to their expression to ER, PR, and HER2/neu. Results There was a statistically significant relation between ER IHC and histopathological type of borderline tumor cases and also between PR IHC and histopathological types of both borderline and malignant tumor cases. A statistically significant relation was found between PR IHC and tumor grade and FIGO stage. Triple-negative tumors are significantly associated with mucinous carcinoma and with FIGO stage IV. Interpretation and conclusion Larger studies on a wider scale of patients, especially those with triple-negative ovarian tumor cases, are needed in order to elucidate the exact role of ER, PR, and HER2/neu as a possible prognostic marker in epithelial OC. Other markers are recommended to be used in association with ER, PR, and HER2/neu in order to improve test sensitivity. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian cancer (OC) is often diagnosed at advanced stages. This study aimed to assess the Palestinian women's knowledge about OC symptoms and determine the factors associated with having good knowledge.Methods: A cross-sectional study was conducted from July 2019 to March 2020 in the two main areas of Palestine: the West Bank and Jerusalem as well as the Gaza Strip. A translated-into-Arabic version of the validated OC awareness measure (OCAM) was utilized for data collection. Stratified convenience sampling was used to recruit adult women attending hospitals, primary healthcare centers, and public spaces at 11 governorates. The knowledge level was categorized into three categories based on the number of symptoms recognized: poor (0 to 4), fair (5 to 8), and good (9 to 11).Results: Of 6095 approached, 5618 participants completed the Arabic OCAM (response rate = 92.1%).A total of 5411 questionnaires were included in the analysis: 2278 from the Gaza Strip and 3133 from the West Bank and Jerusalem. Participants living in the West Bank and Jerusalem were older, of higher monthly income, and with more chronic diseases than those living in the Gaza Strip. The most frequently identified symptoms were 'extreme generalized fatigue' (n = 3821, 70.6%), 'unexplained weight loss' (n = 3607, 66.7%), and 'increased abdominal size on most days' (n = 3252, 60.1%). On the other hand, the least recognized symptoms were 'feeling full persistently' (n = 1553, 28.7%) and 'difficulty eating on most days' (n = 1971, 36.4%). Only 943 participants (17.4%) displayed good knowledge of OC symptoms. Participants from the Gaza Strip had a higher likelihood than participants from the West Bank and Jerusalem to have a good level of knowledge (21.0% vs. 14.8%). Being married, knowing someone with cancer, and visiting hospitals were all associated with a higher likelihood of having good knowledge level. However, living in the West Bank and Jerusalem was associated with a lower likelihood of having good knowledge.Conclusion: The overall knowledge of OC symptoms in this study was low. Educational interventions are needed to improve Palestinian women's knowledge about OC symptoms. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the most prevalent pathologies in gynaecology. This malignancy can be divided into 2 large groups: epithelial and non-epithelial. Because epithelial ovarian cancers (EOC) are the most commonly diagnosed, this paper focuses on the latest therapies associated with this disease. Due to the difficult diagnosis, EOC is frequently detected in the advanced stage. The treatment is usually complex and requires specialist knowledge. Advances and new ideas, such as identification of various genes and molecules that can serve as prognostic factors, might increase patients' chances of survival; they may contribute to optimization of patients' treatment, deciding whether to use aggressive treatment strategies, and predicting chemoresistance. Moreover, new strategies might also improve the quality of life of patients. The study aimed to analyse and discuss the latest reports on new methods of managing EOC. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the leading cause of mortality among all gynecological cancers in developed countries and its most common and most lethal type is the high-grade serous ovarian carcinoma (HGSC). At the molecular level, nearly half of all HGSCs exhibit ineffective homologous DNA recombination and disruption of DNA damage/repair pathway inactivation caused often by BRCA1 and BRCA2 gene mutation. Recently, the detection of BRCA1/2 mutations became important for personalized treatment of HGSC patients with the PARP-inhibitors in the defined clinical setting of relapse after positive adjuvant platinum-based chemotherapeutic response. Based on the selection of patients by regional oncologists, we attempted to verify the possibilities of BRCA1/2 mutation testing on archival formalin-fixed paraffin-embedded (FFPE) biopsy material from regional hospitals. In the study we used: a/ FFPE tumor resections of 97 patients sent to our laboratory, originally stored in archives of regional departments for a period of 1-3 years and retrieved on the principle to contain a maximum of non-necrotic tumor tissue, b/ next-generation sequencing (NGS) assay covering all known mutations in the BRCA1/2 genes on MiSeq (Illumina® platform), and c/ Sophia DDM® bioinformatics platform. After processing of FFPE samples, 5 cases were excluded due to the insufficient genomic DNA quantity. Bioinformatics results of NGS analyses of 92 patients' samples indicated 17.39% pathogenic mutations and 32.61% potentially pathogenic mutations in genes BRCA1/2. Overall, 50% pathogenic and potentially pathogenic mutations were detected in the patient's cohort. The relatively high incidence of BRCA1/2 mutations in our series may be influenced by various indicators including the selection of patients based on adjuvant therapy response as well as regional or population heterogeneity in their frequency. Based on the interdisciplinary cooperation, the use of archival biopsy material processed primarily and stored for a longer period in different laboratories without uniformly defined pre-analytical conditions allows identifying the HGSC patients who might better respond to the PARP-inhibition therapy. [ABSTRACT FROM AUTHOR]

Background: To evaluate the performance of a decision support system (DSS) based on radiomics and machine learning in predicting the risk of malignancy of ovarian masses (OMs) from transvaginal ultrasonography (TUS) and serum CA-125. Methods: A total of 274 consecutive patients who underwent TUS (by different examiners and with different ultrasound machines) and surgery, with suspicious OMs and known CA-125 serum level were used to train and test a DSS. The DSS was used to predict the risk of malignancy of these masses (very low versus medium-high risk), based on the US appearance (solid, liquid, or mixed) and radiomic features (morphometry and regional texture features) within the masses, on the shadow presence (yes/no), and on the level of serum CA-125. Reproducibility of results among the examiners, and performance accuracy, sensitivity, specificity, and area under the curve were tested in a real-world clinical setting. Results: The DSS showed a mean 88% accuracy, 99% sensitivity, and 77% specificity for the 239 patients used for training, cross-validation, and testing, and a mean 91% accuracy, 100% sensitivity, and 80% specificity for the 35 patients used for independent testing. Conclusions: This DSS is a promising tool in women diagnosed with OMs at TUS, allowing to predict the individual risk of malignancy, supporting clinical decision making. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is one of the most common malignancies often resulting in a poor prognosis. 5-methylcytosine (m5C) is a common epigenetic modification with roles in eukaryotes. However, the expression and function of m5C regulatory factors in ovarian cancer remained unclear. Results: Two molecular subtypes with different prognostic and clinicopathological features were identified based on m5C regulatory factors. Meanwhile, functional annotation showed that in the two subtypes, 452 differentially expressed genes were significantly related to the malignant progression of ovarian cancer. Subsequently, four m5C genes were screened to construct a risk marker predictive of overall survival and indicative of clinicopathological features of ovarian cancer, also the robustness of the risk marker was verified in external dataset and internal validation set. multifactorial cox regression analysis and nomogram demonstrated that risk score was an independent prognostic factor for ovarian cancer prognosis. Conclusion: In conclusion, our results revealed that m5C-related genes play a critical role in tumor progression in ovarian cancer. Further detection of m5C methylation could provide a novel targeted therapy for treating ovarian cancer. [ABSTRACT FROM AUTHOR]

Laboratory-markers of the systemic inflammatory-response, such as neutrophil/lymphocyte-ratio (NLR) have been studied as prognostic factors in several tumors but in OC-patients their role is still controversial and no data about the possible correlation with the BRCA-status has been ever reported. We consecutively enrolled a series of 397 newly diagnosed high-grade serous-advanced OC-patients. All patients were tested for BRCA-mutational-status and blood-parameters have been collected 48 h before staging-surgery. A significant correlation of NLR with disease distribution (p < 0.005) was found and patients with NLR < 4 underwent primary-debulking-surgery more frequently (p-value 0.001), with a lower surgical-complexity-score (p-value 0.002). Regarding survival-data, patients with NLR < 4 had a significant 7-month increase in mPFS (26 vs 19 months, p = 0.009); focusing on the BRCA-status, among both BRCA-mutated and BRCA-wild type patients, those with lower NLR had a significantly prolonged mPFS compared to patients with NLR > 4 (BRCA-mutated: 35 vs 23 months, p = 0.03; BRCA-wt: 19 vs 16 months, p = 0.05). At multivariate-analysis, independent factors of prolonged PFS were BRCA mutational status, having received complete cytoreduction and NLR < 4. Also, the strongest predictors of longer OS were BRCA-mutational status, having received complete cytoreductive surgery, NLR < 4 and age. NLR is confirmed to be a prognostic marker in OC-patients and it seems unrelated with BRCA-mutational status. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the efficiency of CA-125, menopausal status, ultrasound features and risk malignancy index in predicting malignancy in patients with an adnexal mass. STUDY DESIGN: This study was designed prospectively and 212 patients who applied to our hospital and met the study criteria were included. Preoperatively RMI value was calculated for the differentiation of benign from malignant patients. The diagnosis was confirmed by histopathology. Kolmogorov- Smirnov, Yates correction, Pearson Chi-Square and Student's t-test were used for statistical analysis. ROC curves were drawn as diagnostic tests and the test results were presented. RESULTS: Of 212 patients included in our study, 174 (82%) patients' were reported as benign, 6 (3%) borderline and 32 (15%) malignant. In predicting malignancy, the malignity risk index with 200 cutoff value the sensitivity and specivity was 87% and 80% respectively. However, when the cutoff value of malignity risk index taken as 112, the sensitivity was unchanged but the specificity increased to 90%. Similarly, when CA-125's cutoff value was taken as 46U/mL, the sensitivity did not change but the specificity increased from 68% to 72%. CONCLUSION: Malignancy risk index is a method that has high sensitivity and specificity. Preoperativeop RMI calculation can provide accurate predictions for the establishment of an appropriate surgical plan for pelvic masses or referral to tertiary centers. [ABSTRACT FROM AUTHOR]

In photoacoustic tomography (PAT), a tunable laser typically illuminates the tissue at multiple wavelengths, and the received photoacoustic waves are used to form functional images of relative total haemoglobin (rHbT) and blood oxygenation saturation (%sO2). Due to measurement errors, the estimation of these parameters can be challenging, especially in clinical studies. In this study, we use a multi‐pixel method to smooth the measurements before calculating rHbT and %sO2. We first perform phantom studies using blood tubes of calibrated %sO2 to evaluate the accuracy of our %sO2 estimation. We conclude by presenting diagnostic results from PAT of 33 patients with 51 ovarian masses imaged by our co‐registered PAT and ultrasound system. The ovarian masses were divided into malignant and benign/normal groups. Functional maps of rHbT and %sO2 and their histograms as well as spectral features were calculated using the PAT data from all ovaries in these two groups. Support vector machine models were trained on different combinations of the significant features. The area under ROC (AUC) of 0.93 (0.95%CI: 0.90‐0.96) on the testing data set was achieved by combining mean %sO2, a spectral feature, and the score of the study radiologist. [ABSTRACT FROM AUTHOR]

Growing evidence suggest that transcription factors (TFs) play vital roles in serous ovarian cancer (SOC). In the present study, TFs mRNA expression profiles of 564 SOC subjects in the TCGA database, and 70 SOC subjects in the GEO database were screened. A 17-TFs related prognostic signature was constructed using lasso cox regression and validated in the TCGA and GEO cohorts. Consensus clustering analysis was applied to establish a cluster model. The 17-TFs related prognostic signature, risk score and cluster models were effective at accurately distinguishing the overall survival of SOC. Analysis of genomic alterations were used to elaborate on the association between the 17-TFs related prognostic signature and genomic aberrations. The GSEA assay results suggested that there was a significant difference in the inflammatory and immune response pathways between the high-risk and low-risk score groups. The potential immune infiltration, immunotherapy, and chemotherapy responses were analyzed due to the significant difference in the regulation of lymphocyte migration and T cell-mediated cytotoxicity between the two groups. The results indicated that patients with low-risk score were more likely to respond anti-PD-1, etoposide, paclitaxel, and veliparib but not to gemcitabine, doxorubicin, docetaxel, and cisplatin. Also, the prognostic nomogram model revealed that the risk score was a good prognostic indicator for SOC patients. In conclusion, we explored the prognostic values of TFs in SOC and developed a 17-TFs related prognostic signature to predict the survival of SOC patients. [ABSTRACT FROM AUTHOR]

Salivary mRNA biomarkers and serum carcinoembryonic antigen (CEA) have been recognized as promising liquid biopsy methods for detection of multiple cancers. However, current tests normally use solitary type of biomarkers, and are limited by unsatisfactory sensitivity and specificity when applied to differentiate cancer patients from healthy controls. In this study, a combined approach of CEA and salivary mRNA biomarkers was evaluated for discriminatory performance of ovarian cancer patients from healthy controls. We designed our study with two phases: a discovery phase to find and evaluate multiple biomarkers, and an independent validation phase to confirm the applicability of the selected biomarkers. In the discovery phase, a total of 140 ovarian cancer patients and 140 healthy controls were recruited. The CEA level in blood as well as five mRNA biomarkers in saliva (i.e. AGPAT1, B2M, BASP1, IER3 and IL1β) were measured, followed by developing a machine-learning model to differentiate ovarian cancer patients and healthy controls. We found a novel panel of biomarkers, which could differentiate ovarian cancer patients from healthy controls with high sensitivity (89.3%) and high specificity (82.9%). Next, we applied this panel of biomarkers in an independent validation study that consisted of 60 ovarian cancer patients and 60 healthy controls. The ovarian cancer patients were successfully differentiated from healthy controls in the validation phase, with sensitivity reaching 85.0% and specificity reaching 88.3%. To our best knowledge, it is the first time that a combined use of CEA and salivary mRNA biomarkers were applied for non-invasive detection of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Surgery remains the main treatment option for an adnexal mass suspicious of ovarian cancer. The malignancy rate is, however, only 10-15% in women undergoing surgery. This results in a high number of unnecessary surgeries. A surveillance-based approach is recommended to form the basis for surgical referrals. We have previously reported the clinical performance of MIA3G, a deep neural network-based algorithm, for assessing ovarian cancer risk. In this study, we show that MIA3G markedly improves the surgical selection for women presenting with adnexal masses., Methods: MIA3G employs seven serum biomarkers, patient age, and menopausal status. Serum samples were collected from 785 women (IQR: 39-55 years) across 12 centers that presented with adnexal masses. MIA3G risk scores were calculated for all subjects in this cohort. Physicians had no access to the MIA3G risk score when deciding upon a surgical referral. The performance of MIA3G for surgery referral was compared to clinical and surgical outcomes. MIA3G was also tested in an independent cohort comprising 29 women across 14 study sites, in which the physicians had access to and utilized MIA3G prior to surgical consideration., Results: When compared to the actual number of surgeries ( n  = 207), referrals based on the MIA3G score would have reduced surgeries by 62% ( n  = 79). The reduction was higher in premenopausal patients (77%) and in patients ≤55 years old (70%). In addition, a 431% improvement in malignancy prediction would have been observed if physicians had utilized MIA3G scores for surgery selection. The accuracy of MIA3G referral was 90.00% (CI 87.89-92.11), while only 9.18% accuracy was observed when the MIA3G score was not used. These results were corroborated in an independent multi-site study of 29 patients in which the physicians utilized MIA3G in surgical consideration. The surgery reduction was 87% in this cohort. Moreover, the accuracy and concordance of MIA3G in this independent cohort were each 96.55%., Conclusion: These findings demonstrate that MIA3G markedly augments the physician's decisions for surgical intervention and improves malignancy prediction in women presenting with adnexal masses. MIA3G utilization as a clinical diagnostic tool might help reduce unnecessary surgeries., Competing Interests: MR, TP, EC, HF, LT, and RP were employed by Aspira Women’s Health and own its stocks. TP was additionally a consultant for Delphi Diagnostics and has options in that company. HF has equity with Apollon PLC, Rokline Health Concepts, Intelymune Inc. and New Day Diagnostic., (Copyright © 2024 Roy Choudhury, Pappas, Twiggs, Caoili, Fritsche and Phan.)

Homologous recombination repair deficiency (HRD) is a frequent feature of high-grade serous ovarian, fallopian tube and peritoneal carcinoma (HGSC) and is associated with sensitivity to PARP inhibitor (PARPi) therapy. HRD testing provides an opportunity to optimise PARPi use in HGSC but methodologies are diverse and clinical application remains controversial. To define best practice for HRD testing in HGSC the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project that incorporated a systematic review approach. The main aims were to (i) define the term 'HRD test'; (ii) provide an overview of the biological rationale and the level of evidence supporting currently available HRD tests; (iii) provide recommendations on the clinical utility of HRD tests in clinical management of HGSC. A broad range of repair genes, genomic scars, mutational signatures and functional assays are associated with a history of HRD. Currently, the clinical validity of HRD tests in ovarian cancer is best assessed, not in terms of biological HRD status per se , but in terms of PARPi benefit. Clinical trials evidence supports the use of BRCA mutation testing and two commercially available assays that also incorporate genomic instability for identifying subgroups of HGSCs that derive different magnitudes of benefit from PARPi therapy, albeit with some variation by clinical scenario. These tests can be used to inform treatment selection and scheduling but their use is limited by a failure to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies. Existing tests lack negative predictive value and inadequately address the complex and dynamic nature of the HRD phenotype. Currently available HRD tests are useful for predicting likely magnitude of benefit from PARPis but better biomarkers are urgently needed to better identify current homologous recombination proficiency status and stratify HGSC management. • Homologous recombination repair deficiency (HRD) is a common feature of high-grade serous gynaecological cancers (HGSC). • Currently, the clinical validity of HRD tests in ovarian cancer is best assessed in terms of PARPi benefit. • Germline and somatic BRCA mutation and genomic instability tests help to predict likely magnitude of benefit from a PARPi. • Existing HRD tests fail to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies. • HRD is a dynamic entity and better biomarkers that capture current homologous recombination proficiency status are needed. [ABSTRACT FROM AUTHOR]

Patients with ovarian cancer are mostly diagnosed at advanced stages which leads to poor prognosis and high mortality rate. Deregulation of lncRNA HOXD-AS1 expression associates with cancer development and metastasis. However, the expression level of this lncRNA in ovarian cancer is not determined.50 paired ovarian tumors and their adjusted normal tissues were included in the study. Total RNA was extracted by TRIzol® Reagent and reverse-transcribed to cDNA using PrimeScript II cDNA synthesis kit. The expression levels of HOXD-AS1 were quantified by qRT-PCR and compared. The Roc curve analysis was used to evaluate the capacity of HOXD-AS1 as a biomarker for ovarian cancer. We observed that lncRNA HOXD-AS1 was significantly upregulated in ovarian tumors compared to their adjusted normal tissues (p<0.003). Moreover, the ROC curve analysis revealed that the lncRNA HOXD-AS1 expression level could discriminate tumoral and non-tumoral tissues with 85% sensitivity and 88% specificity. The lncRNA HOXD-AS1 expression level might be considered as a potential biomarker for ovarian cancer development. [ABSTRACT FROM AUTHOR]

Objective Although trials of neoadjuvant chemotherapy in ovarian cancer use 3 neoadjuvant cycles, real-world practice varies. We sought to evaluate the influence of increasing pre-operative cycles on survival, accounting for surgical outcomes. Methods We identified 199 women with newly diagnosed ovarian cancer recommended for neoadjuvant chemotherapy who underwent interval debulking surgery from July 2015 to December 2018. Non-parametric tests were used to compare clinical characteristics by neoadjuvant cycles. The Kaplan--Meier method was used to estimate differences in progression-free and overall survival. The log-rank test was used to assess the relationship of covariates to outcome. Results The median number of neoadjuvant cycles was 4 (range 3--8), with 56 (28%) women receiving ≥5 cycles. Compared with those receiving 3 or 4, women with ≥5 neoadjuvant cycles received fewer or no post-operative cycles (p<0.001) but had no other differences in clinical factors (p>0.05). Complete gross resection rates were similar among those receiving 3, 4, and ≥5 neoadjuvant cycles (68.5%, 70%, and 71.4%, respectively, p=0.96). There were no significant differences in progressionfree or overall survival when comparing 3 versus 4 neoadjuvant cycles. However, more cycles (≥5 vs 4) were associated with worse progression-free survival, even after adjustment for BRCA status and complete gross resection (HR 2.20, 95% CI 1.45 to 3.33, p<0.001), and worse overall survival, even after adjustment for histology, response on imaging, and complete gross resection rates (HR 2.78, 95% CI 1.37 to 5.63, p=0.016). The most common reason for receiving ≥5 cycles was extent of disease requiring more neoadjuvant chemotherapy. Conclusions Despite maximal cytoreduction, patients receiving ≥5 neoadjuvant cycles have a poorer prognosis than those receiving 3--4 cycles. Future studies should focus on reducing surgical morbidity and optimizing novel therapies in this high-risk group. [ABSTRACT FROM AUTHOR]

Ovarian malignancy has the highest mortality rate for all women with genital cancer because of late diagnosis, tumor heterogeneity, rapid growth and development and resistance to chemotherapy. This study aims to assess the effectiveness of artemisinin as a treatment for ovarian cancer disease. In this study, cases were divided into three groups, the first group contains thirty women with ovarian cancer from the third stage, the second group contains thirty women with ovarian cancer from the fourth stage and the third group contains thirty healthy women. All of them were chosen to study the differences in the biochemical level of ovarian cancer in the sera. Cancer antigen 125 (CA125), Vascular Endothelial Growth Factor A (VEGFA), and Cyclooxygenase_2 (COX-2) were measured in the sera. A significant height was found when measuring CA125, VEGFA, and COX_2. However, when adding artemisinin, very significant decreases in CA125 and VEGFA concentrations have been observed. Also, a decrease in COX_2 activity has been observed. This study was seen increasing COX-2, VEGFA, and CA125, and after adding artemisinin we notice a significant decrease in COX-2, VEGFA, and CA125. [ABSTRACT FROM AUTHOR]

Ovarian cancer refers to any cancerous growth that begins in the ovary. It is difficult to detect, especially in the early stages due to its vague symptoms. Thus, silent killer is a name that has been given to this cancer. Knowledge on the risk factors of ovarian cancer will help in early detection and better prognosis. The aim of this study is to evaluate the level of awareness on the risk factors of ovarian cancer among post menopausal women. A self-administered questionnaire was designed and consisted of questions regarding the awareness on various risk factors of ovarian cancer. The questionnaire was distributed through an online forum. The study population included 100 menopausal women belonging to age groups 40-70years. The questions were carefully studied and the corresponding answers were marked by the participants. The data were collected and statistically analyzed using SPSS software. The results show that the level of awareness on risk factors of ovarian cancer among post menopausal women was less. Majority of the participants were aware that age is a risk factor for ovarian cancer. The most recognised ovarian cancer risk factors among the participants were severe menstrual pain (53%), infertility (48%), hormone replacement therapy (43%) and the least recognised risk factors were usage of birth control pills (36%) and changes in bowel habits (28%). Within the limitations of this study it can be concluded that the overall low level of awareness on risk factors of ovarian cancer among post menopausal women. [ABSTRACT FROM AUTHOR]

The aim of this paper was to find out the association of relevant factors on health-related quality of life (HRQOL) among ovarian cancer patients and their ability to work. Analyzed data were prospectively collected on 123 ovarian cancer patients enrolled across multiple oncology practices in Slovakia. We examined knowledge about the disease, negative perceptions related to health care, ability to work and social and economic ranking. HRQOL measurements included quality of life based on a numeric scale (1-worst, 10-best) and selected aspects from QoL-Ov28 questionnaire. We have used non-parametric Friedman and Dunne pairwise comparison tests to detect differences in HRQOL and the ability to work. Spearman correlation was used to measure the strength of association between variables. With hindsight, patients identified first signs of disease 3.6 months prior to diagnosis, with median duration of disease being 3.1 years. HRQOL was significantly different at various points during cancer journey; between current state and at diagnosis (4.19), between current state and at time without cancer or at time in full health (8.94, 9.52 respectively). Similarly, significant differences were noted in patients' current work ability (WA) compared to WA at diagnosis, or at time without cancer or in full health (4.2, 9.07, 9.58). The highest correlation of HRQOL was found in relation to current ability to work (r = 0.87) and in impact of cancer treatment (r = 0.66). Medium correlation was noted with visits to oncology clinics, knowledge about cancer, salary, future expectations or perceived quality of life of relatives (r < 0.51). Low correlation (r < 0.3) was found with other aspects related to healthcare (nursing care, general practitioner appointments) or demographics (age, number of children) and others. Patients were willing to pay monthly for curative treatment €191.84 from an average monthly salary €470.84 (41%). Ovarian cancer diagnosis has a significant impact on HRQOL and WA and both are positively highly correlated. Ovarian cancer patients are willing to give significant share of their monthly salary for treatment leading to cure. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is one of the most common tumors in females. Growing evidence shows that microRNA-506-3p (miR-506-3p) is downregulated in OC tissues. The purpose of this study was to investigate the mechanism of miR-506-3p in modulating OC. Quantitative reverse transcriptase PCR (qRT-PCR) was employed to investigate the expression of miR-506-3p and its target in OC tissues or cell lines. CCK-8 or colony formation assay was used to examine cell viability or proliferation, respectively. Flow cytometry was demonstrated to detect cell apoptosis. Western blot was then applied to analyze underlying mechanisms. The potential target of miR-506-3p was examined via luciferase reporter assay. MiR-506-3p was significantly downregulated in both human OC tissues and cell lines. Overexpression of miR-506-3p not only decreased cell viability of OC cell lines but also promoted cell apoptosis, thus inhibiting OC progression. Moreover, SIRT1 (Sirtuin 1) was found to be a direct target of miR-506-3p, and SIRT1 expression was negatively regulated by miR-506-3p in OC cell lines. Further investigation revealed that overexpression of SIRT1 could promote cell viability as well as inhibit cell apoptosis, showing the reversed effect on OC progression compared to miR-506-3p. Lastly, AKT (Protein kinase B) /FOXO3a (Forkhead box O3) signaling pathway was inactivated by miR-506-3p while activated by SIRT1, relating to regulation of miR-506-3p on OC progression. Our results revealed a novel mechanism by which miR-506-3p inhibited proliferation while promoted apoptosis of OC via inactivation of SIRT1/AKT/FOXO3a signaling pathway, suggesting that miR-506-3p might be a potential target for OC. [ABSTRACT FROM AUTHOR]

Pre-operative discrimination of malignant masses is crucial for accurate diagnosis and prompt referral to a gynae oncology centre for optimal surgical intervention. HGSOC progression is correlated with local and systemic inflammation. We hypothesised that inclusion of inflammatory biomarkers in sera may improve diagnostic tests. In the training cohort, we tested four existing clinical tests (RMI score and ROMA, CA125 and HE4) and a panel of 28 immune soluble biomarkers in sera from 66 patients undergoing surgery for suspected ovarian cancer. Six promising immune biomarkers alone, or in combination with conventional tests, were subsequently analysed in an independent validation cohort (n = 69). IL-6 was identified as the main driver of variability followed closely by conventional diagnostic tests. Median sera IL-6 was higher in HGSOC patients compared to those with a benign mass or controls with normal ovaries (28.3 vs 7.3 vs 1.2 pg/ml, p < 0.0001). The combination of IL-6 further improved the overall predictive probability of the conventional tests. Modelling a two-step triage of women with a suspicious ovarian mass, with IL-6 > 3.75 pg/ml as primary triage followed by conventional tests (CA125 or RMI score) identified ovarian cancer in patients with a misclassification rate of 4.54–3.03%, superior to the use of CA125 or RMI alone (9.09 to 10.60). The validation cohort demonstrated a similar improvement in the diagnostic sensitivity following addition of IL-6. IL-6 in combination with conventional tests may be a useful clinical biomarker for triage of patients with a suspected malignant ovarian mass. [ABSTRACT FROM AUTHOR]

Objectives In non-gynecologic cancers, clinical trial participation has been associated with aggressive care at the end of life. The objective of this investigation was to examine how trial participation affects end of life outcomes in patients with ovarian cancer. In a retrospective review of women diagnosed with ovarian cancer at our institution between January 2010 and December 2015, we collected variables identified by the National Quality Forum as measures of aggressive end of life care including chemotherapy in the last 14 days of life, intensive care unit (ICU) admission in the last 30 days of life, or death in the acute care setting. Trials investigating medications but not surgical interventions were included. The primary outcome of this study was the association between trial participation and the National Quality Forum measures of aggressive end of life care in ovarian cancer decedents. Data were analyzed with univariable and multivariable parametric and non-parametric testing, and time to event outcomes were analyzed using the Kaplan-Meier method and Cox's proportional hazard models. Results Among 391 women treated for ovarian cancer, 62 patients (16%) participated in a clinical trial. Patients enrolled in clinical trials were more likely to have chemotherapy administered within 14 days of death; however, no association was found with other metrics of aggressive care at the end of life including the initiation of a new chemotherapy regimen in the last 30 days of life, ICU admissions, and death in an acute care setting. Among patients with recurrent ovarian cancer, median overall survival for trial participants was 57 months compared with only 31 months in non-trial participants (p<0.001). Conclusions In patients with ovarian cancer, clinical trial enrollment is associated with chemotherapy administration within 14 days of death, but not other measures of aggressive care at the end of life. Given the importance of clinical trial participation in improving care for women with ovarian cancer, this study suggests that concerns regarding aggressive care prior to death should not limit clinical trial participation. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the diseases that have the highest mortality rate for women, especially women over 50 years old. In the future, incidence and mortality rates are predicted to extend in countries with low HDI. Instability in the structure and function of genetic factors has long been known as a cause of cancer, including ovarian cancer. Besides understanding gene mutations, epigenetic alterations have emerged as another aspect leading to the pathogenesis of ovarian neoplasm. The development and progression of this fatal disease have been found to be associated with abnormalities of epigenetic regulation. DNA methylation, histone modification, and non-coding RNAs-based gene silencing are processes of interest in developing ovarian carcinoma and are also new targets for cancer detection or treatment., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Unusual clinical course. Background: Metachronous ovarian metastasis from primary colorectal cancer (CRC) is a rare condition that is diagnosed after the treatment of CRC. In most cases, ovarian metastases present without specific symptoms or signs and are usually diagnosed during follow-up imaging. A rare case is presented of metachronous ovarian metastasis from primary CRC, diagnosed on follow-up by computed tomography (CT) and magnetic resonance imaging (MRI), and includes a review of the literature. Case Report: A 66-year-old woman recently underwent a left hemicolectomy for a stage T3, N0, M0 primary adenocarcinoma of the sigmoid colon, which was completely excised. Three years later, follow-up CT and MRI imaging showed a right ovarian cyst. She underwent exploratory laparotomy and bilateral salpingo-oophorectomy, which identified tumor in the right ovary. Histopathology and immunohistochemistry confirmed metachronous ovarian metastasis from CRC. The patient was referred for further treatment. Conclusions: Newly-diagnosed ovarian metastasis from primary colorectal cancer (CRC) is challenging to diagnose and manage, and may initially be incorrectly diagnosed as malignancy of primary ovarian origin. This case demonstrated that it is important to confirm the diagnosis with imaging, histology, and the appropriate use of tumor markers. Because ovarian metastases do not respond favorably to chemotherapy, the treatment of choice is surgery. However, for women who are treated for CRC, the use of prophylactic oophorectomy remains controversial. [ABSTRACT FROM AUTHOR]

Sensitive detection of early ovarian cancer is imminent for women's health. Human epididymis specific protein 4 antigen (HE4 Ag), as a novel tumor marker, has good specificity and sensitivity in ovarian cancer markers, especially for the detection of early ovarian cancer. In this work, a novel and ultrasensitive sandwich-type amperometric electrochemical immunosensor was constructed using amine modified graphene supported gold nanorods (Au NRs/NH 2 -GS) as a sensor platform and core-shell Au@Pd urchin-shaped nanostructures (Au@Pd USs) as a label of the secondary antibodies (Ab 2 , Au@Pd USs-Ab 2) to realize the quantitative determination of HE4 Ag. The Au NRs/NH 2 -GS were used for increasing the electrode surface area and effectively immobilizing primary antibodies (Ab 1) due to its good water-solubility. The Au@Pd USs have special morphology with high crystal surface index and good stability, capable of loading secondary antibodies (Ab 2) and providing a larger active site for the catalysis of hydrogen peroxide (H 2 O 2). The proposed immunosensor displays excellent performance for HE4 Ag detection over the range from 1 pmol L−1 to 50 nmol L−1 with a detection limit of 0.33 pmol L−1 (signal-to-noise ratio of 3). Moreover, the designed immunosensor exhibits excellent reproducibility, selectivity, and stability, which shows great potential in clinical diagnosis. A novel and ultrasensitive sandwich-type electrochemical immunosensor was constructed using amine modified graphene supported gold nanorods (Au NRs/NH 2 -GS) as sensor platform and the improved electrocatalytic bimetallic Au@Pd urchin-shaped nanostructures (Au@Pd USs) as label for the quantitative determination of human epididymis specific protein 4 antigen (HE4 Ag). Image 1 • Au@Pd USs were synthesized by a safe, energy-saving and convenient method. • Au@Pd USs with good electrocatalytic were applied as label for quantitative determination of HE4 Ag for the first time. • Au NRs/NH 2 -GS were used as sensor platform to immobilize antibodies and provided a benign microenvironment. • The novel enzyme-free immunosensor exhibited a good analytical performance. [ABSTRACT FROM AUTHOR]

Endometriosis is a precancerous condition for endometriosis-associated ovarian cancer (EAOC). In the present study, conventional magnetic resonance imaging (MRI) and MR relaxometry were used to examine a case of clear cell carcinoma that arose in a pre-existing right-sided benign ovarian endometrioma (OE). The 42-year-old nulliparous woman suspected of EOAC, as assessed by conventional MRI, requested fertility-sparing surgery such as laparoscopic endometrioma cystectomy. Furthermore, the MR transverse relaxation rate (R2) was determined using a single-voxel, multi-echo MR sequence using a 3 Tesla-MR system. An R2 value <12.1 s−1 was indicative of malignancy, as described in previous studies. In the present study, MR relaxometry identified an R2 value of 7.98 s−1 in the right cyst, which suggested the malignant transformation of benign OE. Based on these findings, fertility-sparing surgery was contraindicated. In conclusion, MR relaxometry may represent a new clinical approach as an adjunctive modality for the diagnosis of EAOC. When patients exhibiting a pelvic mass suspected of EAOC desire fertility-sparing treatment options, MR relaxometry can facilitate the selection of conservative management. [ABSTRACT FROM AUTHOR]

Pharmacological inhibition of PARP is a promising approach in treating high grade serous ovarian carcinoma (HGSOC). PARP inhibitors (PARPi) are most active in patients with defects in DNA damage repair (DDR) mechanisms, such as alterations in expression/function of DNA repair and homologous recombination (HR) genes/proteins, including BRCA1 and BRCA2. Benefit of PARPi could be extended towards HR-proficient patients by combining PARPi with agents that functionally abrogate HR. An attractive molecular target for this purpose is heat shock protein 90 (HSP90), which mediates the maturation and stability of several key proteins required for DDR. Here, we tested the hypothesis that targeted inhibition of HSP90 with a small-molecule inhibitor ganetespib would sensitize non-BRCA mutant ovarian carcinoma (OC) cells to PARP inhibition by talazoparib. We used commercially available cell lines, along with several novel HGSOC OC cell lines established in our laboratory. Ganetespib treatment destabilized HSP90 client proteins involved in DNA damage response and cell cycle checkpoint, and disrupted γ-irradiation-induced DNA repair. The effects of the combination of ganetespib and talazoparib on OC cell viability and survival were also analyzed, and among the non-BRCA mutant cell lines analyzed, the combination was synergistic in several cell lines (OVCAR-3, OC-1, OC-16). Together, our data suggest that ganetespib-mediated inhibition of HSP90 effectively disrupts critical DDR pathway proteins and may sensitize OC cells without 'BRCAness' to PARPi. From a clinical perspective, this suggests that HSP90 inhibition has the potential to sensitize some HGSOC patients without HR pathway alterations to PARPi, and potentially other DNA-damage inducing agents. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinicopathological features and chemotherapy response of ovarian clear cell carcinoma (CCC) and endometrioid carcinoma (EC) associated with endometriosis or not. Methods: This was a retrospective study of 128 patients diagnosed with CCC and EC from 2002 to 2017. Clinicopathological features and chemotherapy response were analyzed. Results:There were 34 women with endometriosis-associated ovarian cancer (EAOC) and 94 with non-endometriosis associated ovarian cancer (non-EAOC) according to Sampson's and Scott's criteria. The mean diagnosis age in the EAOC group was 48.65 vs. 54.39 years in non-EAOC (p = 0.002). Compared with non-EAOC, the EAOC patients were more likely to have an earlier menarche age (13 vs. 14 years, p = 0.001), a higher incidence of infertility (26.47% vs. 10.64%, p = 0.026), and an earlier stage tumor (91.18% vs. 73.40% in stages I–II, p = 0.032). At a median follow-up time of 32.9 months, overall survival among patients with EAOC was significantly longer (109.8 vs. 47.4 months, p = 0.007). Association with endometriosis (p = 0.033) was the significant favorable prognostic factors associated with survival. However, stratifying by stage, the overall survival advantage of EAOC was not significant. Although EAOC had a better prognosis, no difference was observed in chemotherapy response between the two groups (p = 0.535). Conclusions: The EAOC patients were often diagnosed at a younger age, an earlier stage, and related to nulliparity and infertility. Patients with EAOC had a better prognosis than non-EAOC, early stage rather than association with endometriosis may be the driver of survival. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A ratiometric ECL biosensor was developed for the analysis of ovarian cancer marker. • A catalytically promoted ECL sensing platform based on NiFe 2 O 4 nanotubes was designed for ratiometric ECL strategy. • Envision complex was introduced into the ratiometric system to enhance the ECL emission process of two luminophors. • The developed ratiometric ECL biosensor exhibited excellent analytical performance in the detection of HE4. Abstract Herein, a delicate ratiometric electrochemiluminescence biosensor was designed for the detection of human epididymis protein 4 (HE4) based on 2-(Dibutylamino)ethanol (DBAE) and lucigenin as anodic and cathodic ECL emitter, respectively. Initially, NiFe 2 O 4 nanotubes (NiFe 2 O 4 NTs) with charming properties could act as catalytically promoted sensing platform. This NiFe 2 O 4 NTs based platform could trigger an intense ECL emission of DBAE for the reason that NiFe 2 O 4 NTs not only achieved the high loading of Envision-Ab 1 complex but effectively catalyzed the oxygen evolution reaction (OER) to yield oxygen. Moreover, the Envision complex, a polymeric material containing enrich horseradish peroxidase (HRP) could further accelerate the H 2 O 2 decomposition to generate superoxide (O 2 −) for the enhancement of the ECL emission process of two luminophors. It's noteworthy that hexagonal boron nitride nanosheets (h-BN) as the nanolabels, was first illustrated to be capable of immobilizing a large quantity of lucigenin and retaining intense and stable ECL emission of lucigenin in the alkaline condition. Benefiting from the above merits, a new ECL ratiometric sensing mode was established for the sensitive determination of HE4 in a range from 10 fg/mL to 10 ng/mL with the detection limit of 3.3 fg/mL. The strategy exhibited broad prospect in early ovarian cancer diagnosis and blazed a new path for other tumors screening. [ABSTRACT FROM AUTHOR]

Multigene panel testing for breast and ovarian cancer predisposition diagnosis is a useful tool as it makes possible to sequence a considerable number of genes in a large number of individuals. More than 200 different multigene panels in which the two major BRCA1 and BRCA2 breast cancer predisposing genes are included are proposed by public or commercial laboratories. We review the clinical validity and clinical utility of the 26 genes most oftenly included in these panels. Because clinical validity and utility are not established for all genes and due to the heterogeneity of tumour risk levels, there is a substantial difficulty in the routine use of multigene panels if management guidelines and recommendations for testing relatives are not previously defined for each gene. Besides, the classification of variant of unknown significance (VUS) is a particular limitation and challenge. Efforts to classify VUSs and also to identify factors that modify cancer risks are now needed to produce personalised risk estimates. The complexity of information, the capacity to come back to patients when VUS are re-classified as pathogenic, and the expected large increase in the number of individuals to be tested especially when the aim of multigene panel testing is not only prevention but also treatment are challenging both for physicians and patients. Quality of tests, interpretation of results, information and accompaniment of patients must be at the heart of the guidelines of multigene panel testing. • Multigene panel allows to sequence a high number of genes in numerous individuals. • Management and relative testing guidelines need to be defined for each gene. • Variant classification is a challenge amplified by NGS. • Quality of tests, information and accompaniment of patients are testing guidelines. • Tumour DNA is the native DNA of the patient!. [ABSTRACT FROM AUTHOR]