Malignant Ovarian Tumors Research Articles

Primary ileal carcinoid presenting with metastatic ovarian tumours and florid carcinoid syndrome: a multidisciplinary care challenge

Primary ileal carcinoid presenting with metastatic ovarian tumours and florid carcinoid syndrome: a multidisciplinary care challenge

Role of magnetic resonance imaging to differentiate between borderline and malignant serous epithelial ovarian tumors.

We aimed to differentiate serous borderline ovarian tumors (SBOT) from serous epithelial ovarian carcinomas (SEOC) using morphological and functional MRI findings, to improve the patient management. We retrospectively investigated 24 ovarian lesions diagnosed with SBOT and 64 ovarian lesions diagnosed with SEOC. Additional to the demographic and morphological findings T2W signal intensity ratio, mean apparent diffusion coefficient (ADCmean) and total apparent diffusion coefficient (ADCtotal) values were analyzed and compared between two groups. Bilaterality, pelvic free fluid presence, serum CA-125 level (U/mL), presence of pelvic peritoneal implant were in favor of SEOC. Lower maximum size of solid component and solid size to maximum size ratio, dominantly cystic and solid-cystic appearance, exophytic growth pattern, presence of papiller projection and papillary architecture and internal branching pattern, higher T2W signal intensity ratio, ADCmean and ADCtotal values were in favor of SBOT. Our study revealed that morphological and functional imaging findings were valuable in differentiating BSOT from SEOC.

Correlation of Heavy Metal Content in the Blood of Patients with Ovarian Cancer by Place of Residence

Introduction. Malignant ovarian tumours are an urgent problem in oncology today. Ovarian cancer (OC) is in the top ten in terms of prevalence, ranking 7th, and in the top five in terms of mortality, ranking 4th. The asymptomatic course of the disease is explained by the progression of ovarian cancer mainly due to peritoneal dissemination; that is the reason why the disease is diagnosed at late stages. The prognosis of the disease depends on its stage, the degree of differentiation of the tumour, the recurrence-free period, the size of the residual tumour after surgical treatment. Taking into account the above factors, this disease is interesting for scientists in terms of finding new factors for predicting its course and trying to influence them. Purpose: increasing the effectiveness of treatment of patients with ovarian cancer by individualizing supportive therapy taking into account the level of heavy metal salts in the blood.
 Methods. The study is based on the results of observation of 127 patients with ovarian cancer of stages I-IV. The duration of recurrence-free survival was studied and evaluated depending on the place of residence of patients with ovarian cancer. Results. The analysis of the recurrence-free survival of patients by the territorial principle was carried out: higher rates of cumulative survival of patients are recorded in virtually all studied intervals in patients living in Ivano-Frankivsk and Kalush districts (where a higher content of Zn in the blood of patients is recorded). Cox regressions in correlation with Zn variables were constructed for them.
 The Cox regression was calculated in correlation with the variables of Zn in the blood of patients with OC living in the Ivano-Frankivsk and Kalush districts at minimal values of the metal content in the blood. For the Ivano-Frankivsk district, it is predicted that at the 16th month of observation, the recurrence-free survival rate will be 0%. For Kolomyia district, the projected recurrence-free survival rate is even lower, with no patients remaining at the 9th month of follow-up. The predicted recurrence-free survival in correlation with Zn variables in the blood of patients with OC living in Ivano-Frankivsk and Kalush districts at the maximum values of the metal in the blood was determined. For the Ivano-Frankivsk district, it is predicted that 97% of patients will remain under observation at month 36. For Kolomyia district, the predicted recurrence-free survival rate at the 36th month of observation is 99%. Conclusions. A correlation was found between the zinc content in the blood of patients with OC and the place of residence in Ivano-Frankivsk region; according to the analysis of the obtained data set, the strongest correlation of recurrence-free survival of patients is observed with this element. Increased levels of zinc and copper in the blood of patients resulted in a longer duration of disease-free survival, so patients from Kalush and Ivano-Frankivsk regions have a more favourable prognosis.
 For chromium and copper, the place of residence of patients doesn’t play any role.

Clinicopathological Features and Survival Trends of Non-Epithelial Ovarian Cancer: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database

Introduction: Owing to their low incidence, no reliable statistics about prognostication derived from large sample sizes have been reported of malignant ovarian germ cell tumors (MOGCTs) and sex cord-stromal tumors (SCSTs). The present study aimed to investigate the clinicopathological prognostic factors and the survival trends of MOGCTs and SCSTs. Materials and Methods: Patients with MOGCTs and SCSTs were recorded in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2000 and 2019. Clinical, demographic, and treatment characteristics were compared between groups of MOGCTs and SCSTs. Cox risk regression analysis and Kaplan-Meier survival curves were used to compare overall survival (OS) and cancer-specific survival (CSS) and to assess the prognostic factors. Results: Information about 2,506 patients with MOGCTs and 1,556 patients with SCSTs was extracted from the SEER database, respectively. Aged <40 years and single were more common in patients with MOGCTs than in those with SCSTs. The vast majority of patients with MOGCTs and SCSTs underwent surgery (98.1% vs. 94.5%; p < 0.001), and women with MOGCTs were more likely to receive chemotherapy than women with SCSTs (56.1% vs. 32.2%; p < 0.001). For both patients before and after propensity-score matching, the 5-year OS rates of patients with SCSTs were lower than those of patients with MOGCTs (p < 0.05). In multivariate Cox regression analysis, both age and surgery were independent predictors of OS in patients with MOGCTs and SCSTs. FIGO staging was an independent predictor of CSS in MOGCT patients. Tumor size and chemotherapy were also independent predictors of CSS in patients with SCSTs. Conclusion: Compared to patients with SCSTs, those with MOGCTs tended to be younger and had a higher OS and CSS. Adjuvant chemotherapy after surgery did not prolong OS and CSS in patients with SCSTs.

Ultrasonographic diagnosis of ovarian tumors through the deep convolutional neural network.

The objective of this study was to develop and validate an ovarian tumor ultrasonographic diagnostic model based on deep convolutional neural networks (DCNN) and compare its diagnostic performance with that of human experts. We collected 486 ultrasound images of 192 women with malignant ovarian tumors and 617 ultrasound images of 213 women with benign ovarian tumors, all confirmed by pathological examination. The image dataset was split into a training set and a validation set according to a 7:3 ratio. We selected 5 DCNNs to develop our model: MobileNet, Xception, Inception, ResNet and DenseNet. We compared the performance of the five models through the area under the curve (AUC), sensitivity, specificity, and accuracy. We then randomly selected 200 images from the validation set as the test set. We asked three expert radiologists to diagnose the images to compare the performance of radiologists and the DCNN model. In the validation set, AUC of DenseNet was 0.997 while AUC was 0.988 of ResNet, 0.987 of Inception, 0.968 of Xception and 0.836 of MobileNet. In the test set, the accuracy was 0.975 with the DenseNet model versus 0.825 (p < 0.0001) with the radiologists, and sensitivity was 0.975 versus 0.700 (p < 0.0001), and specificity was 0.975 versus 0.908 (p < 0.001). DensNet performed better than other DCNNs and expert radiologists in identifying malignant ovarian tumors from benign ovarian tumors based on ultrasound images, a finding that needs to be further explored in clinical trials.

Group penalized logistic regression differentiates between benign and malignant ovarian tumors

Group penalized logistic regression differentiates between benign and malignant ovarian tumors

Disabled-2: a protein up-regulated by high molecular weight hyaluronan has both tumor promoting and tumor suppressor roles in ovarian cancer

Although the pro-tumorigenic functions of hyaluronan (HA) are well documented there is limited information on the effects and targets of different molecular weight HA. Here, we investigated the effects of 27 kDa, 183 kDa and 1000 kDa HA on ES-2 ovarian cancer cells overexpressing the stem cell associated protein, Notch3. 1000 kDA HA promoted spheroid formation in ES-2 cells mixed with ES-2 overexpressing Notch3 (1:3). We report disabled-2 (DAB2) as a novel protein regulated by 1000 kDa HA and further investigated its role in ovarian cancer. DAB2 was downregulated in ovarian cancer compared to normal tissues but increased in metastatic ovarian tumors compared to primary tumors. High DAB2 expression was associated with poor patient outcome and positively correlated with HA synthesis enzyme HAS2, HA receptor CD44 and EMT and macrophage markers. Stromal DAB2 immunostaining was significantly increased in matched ovarian cancer tissues at relapse compared to diagnosis and associated with reduced survival. The proportion of DAB2 positive macrophages was significantly increased in metastatic ovarian cancer tissues compared to primary cancers. However, DAB2 overexpression significantly reduced invasion by both A2780 and OVCAR3 cells in vivo. Our research identifies a novel relationship between HA signalling, Notch3 and DAB2. We highlight a complex relationship of both pro-tumorigenic and tumor suppressive functions of DAB2 in ovarian cancer. Our findings highlight that DAB2 has a direct tumor suppressive role on ovarian cancer cells. The pro-tumorigenic role of DAB2 may be mediated by tumour associated macrophages and requires further investigation.

OR16-06 A Novel Pathway Controlling Anticancer Drug Induced Immunogenic Necrosis In ERα Positive Cancer Cells

Abstract Disclosure: J. Zhu: None. S. Ghosh: None. D. Duraki: None. M. Boudreau: Other; Self; Patent on ErSO. M. Jabeen: None. C. Mao: None. B. Park: None. G. Cheng: None. E.R. Nelson: None. P.J. Hergenrother: Advisory Board Member; Self; System Oncology. Other; Self; Patent on ErSO. D.J. Shapiro: Other; Self; Patent on ErSO. Acting through estrogen receptor alpha (ER), in orthotopic mouse xenograft models and a PDX, our non-competitive anticancer drug ErSO induces complete or near complete regression of primary and metastatic therapy-resistant ERα-positive breast, ovarian and endometrial tumors. ErSO is also highly effective in ovarian cancer PDOs from patient ascites. Unlike most anticancer agents which inhibit cancer cell proliferation or induce apoptosis, ErSO induces immune-cell-activating necrosis through ERα dependent sustained hyperactivation of the anticipatory unfolded protein response (a-UPR) pathway resulting in ATP depletion and cell swelling followed by membrane rupture and necrotic cell death. The medium from cancer cells killed by ErSO not only robustly activates mouse and human macrophages, but also dramatically increases monocyte migration. ErSO therefore has the potential to help extend the reach of immunotherapy to many solid tumors that do not express neoantigens. However, unlike apoptosis which has an established signaling pathway, how ErSO-induced necrosis was elusive. From a genome-wide CRISPR-Cas9 screen in MCF7 cells with negative selection against ErSO, we identified a guanine exchange factor (GEF) protein as a top target. Consistent with the screen, through subsequent knockout and overexpression of this protein in human breast cancer cells, we found that the knockout cells have significant resistance to ErSO while the overexpressing cells exhibit increased sensitivity to killing by ErSO. Our data indicates that this protein is not an upstream regulator of the ErSO-induced necrosis pathway. Instead, it is a regulator of the last stage of necrosis - cell membrane rupture. Thus, we identified a cytoskeleton-modifying signaling pathway with multiple components that plays a pivotal role in whether the breast cancer cell responds to a-UPR activation and swelling by membrane rupture and necrotic cell death or reorganizes its cytoskeleton enabling the cancer cell to survive. RNA-seq and other studies indicate that by regulating cytoskeleton organization, this axis is important in ErSO-persister breast cancer cells exhibiting long-term survival in ErSO. Unlike wild type and overexpressing cells, the knockout cells and persister cells display the persister cell phenotype - rapid re-growth of the cancer cells once ErSO is removed. This work enables identification of breast cancer patients whose elevated levels of components of this signaling pathway make them most likely to benefit from this novel therapy. Here, we describe a therapy that induces necrosis and immunogenic cell death in ERα-positive breast, ovarian and endometrial cancer cells. We show that, as cancer cells respond to this unique therapeutic approach, a cytoskeleton regulating pathway plays a critical role in life-death decisions. Presentation: Friday, June 16, 2023

Revised Cut-Off Value of Human Epididymis Protein 4 Enhances Its Use as an Ovarian Tumor Marker

Objectives: Human epididymis protein 4 (HE4), a protein secreted by ovarian tumors, has been used as an ovarian tumor marker. This study aimed to improve the usefulness of HE4 to detect malignant ovarian tumors by reviewing the cut-off values. Design: A retrospective study without intervention was conducted. Participants: One hundred forty-nine healthy women (premenopausal, 126; postmenopausal, 23) and 24 patients with ovarian tumors (malignant, 12; benign, 12) participated in the study. Setting: The study used the Department of Obstetrics and Gynecology of a university hospital in Japan and the university hospital as a workplace from 2016 to 2018. Methods: The basic performance of the HE4 assay was evaluated, and the serum HE4 levels of participants were measured. Receiver operating characteristic analysis was performed using the HE4 data of the patients. Results: There were no significant differences in HE4 levels between the pre- and postmenopausal groups of healthy women. When the global cut-off values (premenopausal, 70 pmol/L; postmenopausal, 140 pmol/L) were adopted, the clinical sensitivity, specificity, positive predictive value, and negative predictive value were 41.7%, 91.7%, 83.3%, and 61.1%, respectively. Based on the results of the receiver operating characteristic analysis, we set the HE4 cut-off level at 60 pmol/L, regardless of the menopausal status. With the newly set cut-off value, the clinical sensitivity, specificity, positive predictive value, and negative predictive value were 66.7%, 91.7%, 88.9%, and 73.3%, respectively. That is, the clinical sensitivity of HE4 was improved without lowering specificity. Limitations: The small number of subjects and the fact that the health status of the healthy women was evaluated based on questionnaires were limitations to the study. Conclusion: A clinically useful cut-off value for HE4 as an ovarian tumor marker was established regardless of the menopausal status of the women, with improved clinical sensitivity, positive predictive value, and negative predictive value without lowering specificity. Currently, different cut-off values for HE4 in pre- and postmenopausal women are used globally. The cut-off value for CA125 was the same between pre- and postmenopausal women. Therefore, with the newly established cut-off value, HE4 can be used more conveniently in a non-specialized setting, especially when it is used in combination with CA125.

Histopathological spectrum of ovarian tumors in tertiary care centre of central India

Abstract Background: Ovarian tumors are common, ranking third in frequency after cervical and uterine cancer. According to the World Ovarian Cancer Coalition Atlas 2018, India has the second-highest incidence of ovarian carcinoma worldwide. In Chhattisgarh, ovarian malignancy accounts for 5.21% of all malignancies in females. Materials and Methods: The present descriptive observational cross-sectional study encompassed 108 cases of ovarian tumors. A histopathological examination was done, and data was compiled and analyzed. Observations and Results: Among the 108 ovarian tumors, 59.25% were noted in women aged 40–59 years. The primary presenting symptom was abdominal pain, reported by 57.40% of the cases. The majority of ovarian tumors were unilateral, the right side being more common. Primary ovarian tumors constituted 91.66%, while 8.33% were classified as secondary or metastatic ovarian tumors. Of 108 cases, 55.5% were malignant, 40.7% were benign, and 3.7% were borderline tumors. Surface epithelial tumors accounted for 73.14% of the cases; germ cell tumors constituted 9.25%, sex cord-stromal tumors were 7.4%, and mesenchymal tumors were 1.85%. Among surface epithelial tumors, serous cystadenocarcinoma was most common. Mature cystic teratoma was the most common germ cell tumor, and granulosa cell tumor was the most common sex cord-stromal tumor. Conclusion: Ovarian tumors were more commonly seen in the peri and postmenopausal age group. Primary malignant epithelial tumors were the most common type of ovarian tumor. The histopathological evaluation of ovarian tumors remains the gold standard for definitive diagnosis.

Critical elements in the operative management of pediatric malignant ovarian germ cell tumors

Performance of the appropriate operation is highly important to ensure that any patient with a suspected ovarian germ cell tumor receives optimal therapy that prioritizes cure while simultaneoulsy minimizing risk of short and long-term toxicities of treatment. The following critical elements of any operative procedure performed for a suspected pediatric or adolescent ovarian germ cell tumor are reviewed: 1. Complete resection of the tumor via ipsilateral oophorectomy while avoiding tumor rupture and spillage, and 2. Performance of complete intraperitoneal staging at the time of initial tumor resection.

Fertility-sparing approach to malignant ovarian germ cell tumors - Oncologic and obstetric outocome: A retrospective study.

To evaluate oncologic (such as disease-free and overall survival) and obstetric outcomes in patients diagnosed with malignant ovarian germ cell tumors (MOGCTs). Patients diagnosed with MOGCTs between March 2007 and February 2022 were evaluated and patients who underwent fertility sparing surgery were included in this retrospective study. The obstetric and oncologic outcomes were evaluated by collecting data up until the patient's last follow-up visit from the hospital records and patient files. The study was approved by Başkent University Institutional Review Board (KA23/124). Seventy FSS patients were included in this study. The median age of the patients was 22.5 years (range: 11-37). The median follow-up time was 92.0 months (10-189). Immature teratoma was the most common histological subtype (32.9%). Bilateral involvement was detected in only one patient with immature teratoma (1.4%). The 5-year DFS rates of immature teratoma, dysgerminoma, yolk sac, and mixed germ cell histologic types were 91.1%, 94.1%, 82.4%, and 88.9%, respectively (P: 0.716). The 5-year OS rates of the same histologic types were 95.7%, 100%, 88.2%, and 88.9%, respectively (P = 0.487). All patients (100%) had a regular menstrual cycle after the completion of adjuvant treatment. The mean time between the last chemotherapy and menstruation was 4.38 months. To date, a total of 34 patients tried to conceive after the completion of disease treatment. A total of 23 (67.6%) patients conceived, resulting in 27 live births in 22 (100%) patients. Fertility preservation should be the first treatment option in MOGCTs in young patients due to the unilateral involvement of the disease and its chemosensitive nature.

Diagnostic roles of PAX8 immunohistochemistry in ovarian tumors

ObjectiveThis study aimed to elucidate the diagnostic roles of PAX8 immunohistochemistry in various ovarian tumors. MethodsWe searched through the PubMed database and selected the eligible studies to perform the meta-analysis. The PAX8 immunohistochemical expression rates of various ovarian tumors, including primary and metastatic carcinomas, were analyzed. In addition, the subgroup analysis based on tumor behaviors was performed. ResultsThe PAX8 expression rates were 0.056 (95% confidence interval [CI] 0.008–0.307), 0.400 (95% CI 0.228–0.600), 0.741 (95% CI 0.578–0.857), and 0.738 (95% CI 0.666–0.799) in normal ovary and benign, borderline, and malignant ovarian tumors, respectively. The PAX8 expression rates of serous and transitional cell carcinomas were 0.937 (95% CI 0.882–0.967) and 0.918 (95% CI 0.841–0.959). In addition, the PAX8 expression rate of mucinous carcinomas was 0.393 (95% CI 0.285–0.512). However, metastatic carcinomas showed a significantly lower PAX8 expression rate than primary ovarian cancers (P < 0.001 in the meta-regression test). In cytologic specimens, PAX8 expression rates of serous and endometrioid carcinomas were 0.905 (95% CI 0.832–0.948) and 0.714 (95% CI 0.327–0.928), respectively. ConclusionPAX8 expression rate was significantly higher in serous ovarian tumors than in mucinous ovarian tumors. In addition, PAX8 expression rates were significantly higher in primary ovarian cancers than in metastatic carcinomas.

Rare malignant tumors of the ovary during pregnancy: a clinical case report

This article describes a clinical case of a malignant ovarian neoplasm, which was first detected during an urgent visit of a pregnant woman with signs of fetal distress in the third trimester of pregnancy. The relevance of this problem lies in the possibility of early diagnosis of adnexal tumors during routine ultrasound screenings, the lack of definitive recommendations for the management of such patients and the limited range of treatment methods during pregnancy. The aim of the study is to demonstrate a clinical case of pregnancy with late-detected ovarian malignancy. A 39-year-old pregnant woman at 35 weeks and 4 days' gestation consulted the antenatal clinic of a city maternity hospital with complaints of a decrease in the number and change in the nature of fetal movements over the past 24 hours. After assessment of the fetal condition (cardiotocography, ultrasound), the woman was hospitalized with a diagnosis: Pregnancy III, 35 weeks and 4 days. Fetal distress in the antenatal period. Fetal growth restriction, stage I. Gestational hypertension without significant proteinuria. Multicompartmental cyst of the right ovary. An urgent cesarean section was performed. Clinical diagnosis: рremature delivery by cesarean section. Medical care for the mother with fetal growth restriction of the first degree, fetal distress in the antenatal period. Cyst of the right ovary. Right-sided adnexectomy. Omental resection. Gestational hypertension. On the 5th day, the patient was discharged in a satisfactory condition with a recommendation for further examination in an oncology hospital. Pathological examination of the right ovary: morphological picture, taking into account the results of immunohistochemical examination, in favor of undifferentiated carcinoma; on repeated viewing - granular cell tumor of the ovary of adult type. The patient was routinely hospitalized at the city oncology center for surgical treatment and further examination. Clinical diagnosis: Bl ovarii gr I, adult-type granulosa cell tumor, T1Nx Mx. Condition after surgical treatment: lower midline laparotomy. Pangisterectomy, omentectomy. Sampling of the retroperitoneal lymph nodes on the right. Sanitation and drainage of the abdominal cavity. Clinical group II. The results of this article are of great practical importance for obstetricians-gynecologists, general surgeons and ultrasound diagnosticians in the differential diagnosis of indirect signs of malignant tumors during pregnancy, in the need to examine all pelvic organs during routine ultrasound screening of pregnant women and in establishing cause and effect relationships in the diagnosis of obstetric complications.

When Thyroid Meets Ovary: A Case Report of Struma Ovarii

Struma Ovarii is not a common tumor. It is a mature ovarian teratoma, completely or predominantly composed of thyroid tissue. It belongs to a specialised monodermal variety. Struma ovarii may have an association with hyperthyroidism; however, it is a rare association and just in about 8% of cases. Its diagnosis is mostly delayed because most of the patients do not present any symptoms. Some patients may develop symptoms of specific conditions like ovarian torsion, hyperthyroidism, and ascites. Ultrasound, MRI, CT scan, and scintigraphic evaluation are necessary to differentiate benign from malignant variety. The first line treatment option is surgical removal. There are lesser chances that the tumor will recur and the quality of life is improved significantly. In this case report, we have discussed a unique case of struma ovarii. It was duly diagnosed and appropriate management was done. The tumor was different from malignant ovarian tumor on the basis of ascites and tumor marker assessments. Thyroid function investigations were also normal. The tumor is incidentally found on imaging in most cases. The definitive diagnosis is established by a histopathological study. The first line of treatment is surgical removal and it usually leads to a successful prognosis. We will determine the challenges that are faced to reach the diagnosis and management of this rare tumor. Misdiagnosis is common. The treatment options are debatable because it is a rare tumor. In fertile and young age groups, fertility conserving surgeries like ovarian cystectomy or unilateral salpingo-oophorectomy are advised. For the purpose of treatment, in postmenopausal cases, total abdominal hysterectomy with bilateral salpingo-oophorectomy may sometimes be indicated. The quality of life will improve if investigations are done early and appropriate management is done.

Prediction of benign and malignant ovarian tumors using Resnet34 on ultrasound images.

To develop deep learning (DL) prediction models using transvaginal ultrasound (TVS), transabdominal ultrasound (TAS), and color Doppler flow imaging (CDFI) of TVS (CDFI_TVS) to automatically predict benign or malignant ovarian tumors. This retrospective study included women with ovarian tumors who underwent ultrasound between August 2018 and October 2022. Histopathological analysis was used as a reference standard. The dataset was preprocessed by clipping, flipping, and rotating images to generate a larger, more complicated, and diverse dataset to improve accuracy and generalizability. The dataset was then divided into training (80%) and test (20%) sets. The weights of the models, modified from the residual network (ResNet) with the TVS, TAS, and CDFI_TVS images (hereafter, referred to as DLTVS , DLTAS , and DLCDFI_TVS , respectively) were developed. The area under the receiver operating characteristic curve (AUC) analysis in the test set was used to compare the predictive value of DL for malignancy. A total of 2340 images from 1350 women with adnexal masses were included. DLTVS had an AUC of 0.95 (95% CI: 0.93-0.97) for classifying malignant and benign ovarian tumors, comparable with that of DLTAS (AUC, 0.95; 95% CI: 0.91-0.98; p = 0.96) and DLCDFI_TVS (AUC, 0.88; 95% CI: 0.84-0.93; p = 0.02). Decision curve analysis indicated that DLTVS performed better than DLTAS and DLCDFI_TVS . We developed DL models based on TVS, TAS, and CDFI_TVS on ultrasound images to predict benign and malignant ovarian tumors with high diagnostic performance. The DLTVS model had the best prediction compared with the DLTAS and DLCDFI_TVS models.

The Contribution of Lipidomics in Ovarian Cancer Management: A Systematic Review.

Lipidomics is a comprehensive study of all lipid components in living cells, serum, plasma, or tissues, with the aim of discovering diagnostic, prognostic, and predictive biomarkers for diseases such as malignant tumors. This systematic review evaluates studies, applying lipidomics to the diagnosis, prognosis, prediction, and differentiation of malignant and benign ovarian tumors. A literature search was performed in PubMed, Science Direct, and SciFinder. Only publications written in English after 2012 were included. Relevant citations were identified from the reference lists of primary included studies and were also included in our list. All studies included referred to the application of lipidomics in serum/plasma samples from human cases of OC, some of which also included tumor tissue samples. In some of the included studies, metabolome analysis was also performed, in which other metabolites were identified in addition to lipids. Qualitative data were assessed, and the risk of bias was determined using the ROBINS-I tool. A total of twenty-nine studies were included, fifteen of which applied non-targeted lipidomics, seven applied targeted lipidomics, and seven were reviews relevant to our objectives. Most studies focused on the potential application of lipidomics in the diagnosis of OC and showed that phospholipids and sphingolipids change most significantly during disease development. In conclusion, this systematic review highlights the potential contribution of lipids as biomarkers in OC management.

Systematic Review of the Survival Outcomes of Neoadjuvant Chemotherapy in Women with Malignant Ovarian Germ Cell Tumors.

Randomized clinical trials assessing the efficacy of neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer have predominantly included women with high-grade serous carcinomas. The response rate and oncological outcomes of NACT for malignant ovarian germ cell tumors (MOGCT) are poorly understood. This study aimed to examine the effects of NACT on women with MOGCT by conducting a systematic review of four public search engines. Fifteen studies were identified, and a further descriptive analysis was performed for 10 original articles. In those studies, most women were treated with a bleomycin, etoposide, and cisplatin regimen, and one to three cycles were used in most studies. Four studies comparing NACT and primary debulking surgery showed similar complete response rates (n = 2; pooled odds ratio [OR] 0.90, 95% confidence interval [CI] 0.15-5.27), comparable overall survival (n = 3; 87.0-100% versus 70.0-100%), disease-free survival (n = 3; 87.0-100% versus 70.0-100%), recurrence rate (n = 1; OR 3.50, 95%CI 0.38-32.50), and adverse events rate from chemotherapy between the groups. In conclusion, NACT may be considered for the management of MOGCT; however, possible candidates for NACT use and an ideal number of NACT cycles remain unknown. Further studies are warranted to validate the efficacy of NACT in advanced MOGCT patients.

Clinical Significance of the TK1-Specific Activity in the Early Detection of Ovarian Cancer

Introduction: Ovarian cancer is the eighth most common cause of cancer death in women. One of the major concerns is almost two-thirds of cases are typically diagnosed in the late stage as the symptoms are unspecific in the early stage of ovarian cancer. It is known that the combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone. That is why, the aim of the study was to investigate whether the TK1-specific activity (TK1 SA) could function as a complement marker for early-stage diagnosis of ovarian cancer. Methods: The study included a set of 198 sera consisting of 134 patients with ovarian tumors (72 benign and 62 malignant) and 64 healthy age-matched controls. The TK1 SA was determined using TK1 activity by TK-Liaison and TK1 protein by AroCell TK 210 ELISA. Further, CA 125, HE4, as well as risk of ovarian malignancy algorithm index were also determined in the same set of clinical samples. Results: The TK1 SA was significantly different between healthy compared to ovarian cancer patients (p < 0.0001). Strikingly, TK1 SA has higher sensitivity (55%) compared to other biomarkers in the detection of benign ovarian tumors. Further, the highest sensitivity was achieved by the combination of TK1 SA with CA 125 and HE4 for the detection of benign tumors as well as malignant ovarian tumors (72.2% and 88.7%). In addition, TK1 SA could significantly differentiate FIGO stage I/II from stage III/IV malignancies (p = 0.026). Follow-up of patients after surgery and chemotherapy showed a significant difference compared to TK1 SA at the time of diagnosis. Conclusions: These results indicate that TK1 SA is a promising blood-based biomarker that could complement CA 125 and HE4 for the detection of early stages of ovarian cancer.

Peripheral Blood Serum NMR Metabolomics Is a Powerful Tool to Discriminate Benign and Malignant Ovarian Tumors.

Ovarian cancer is the major cause of death from gynecological cancer and the third most common gynecological malignancy worldwide. Despite a slight improvement in the overall survival of ovarian carcinoma patients in recent decades, the cure rate has not improved. This is mainly due to late diagnosis and resistance to therapy. It is therefore urgent to develop effective methods for early detection and prognosis. We hypothesized that, besides being able to distinguish serum samples of patients with ovarian cancer from those of patients with benign ovarian tumors, 1H-NMR metabolomics analysis might be able to predict the malignant potential of tumors. For this, serum 1H-NMR metabolomics analyses were performed, including patients with malignant, benign and borderline ovarian tumors. The serum metabolic profiles were analyzed by multivariate statistical analysis, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) methods. A metabolic profile associated with ovarian malignant tumors was defined, in which lactate, 3-hydroxybutyrate and acetone were increased and acetate, histidine, valine and methanol were decreased. Our data support the use of 1H-NMR metabolomics analysis as a screening method for ovarian cancer detection and might be useful for predicting the malignant potential of borderline tumors.