MR-based radiomics-clinical nomogram in epithelial ovarian tumor prognosis prediction: tumor body texture analysis across various acquisition protocols

Background Epithelial ovarian cancer (EOC) is the most malignant gynecological tumor in women. This study aimed to construct and compare radiomics-clinical nomograms based on MR images in EOC prognosis prediction. Methods A total of 186 patients with pathologically proven EOC were enrolled and randomly divided into a training cohort (n = 130) and a validation cohort (n = 56). Clinical characteristics of each patient were retrieved from the hospital information system. A total of 1116 radiomics features were extracted from tumor body on T2-weighted imaging (T2WI), T1-weighted imaging (T1WI), diffusion weighted imaging (DWI) and contrast-enhanced T1-weighted imaging (CE-T1WI). Paired sequence signatures were constructed, selected and trained to build a prognosis prediction model. Radiomic-clinical nomogram was constructed based on multivariate logistic regression analysis with radiomics score and clinical features. The predictive performance was evaluated by receiver operating characteristic curve (ROC) analysis, decision curve analysis (DCA) and calibration curve. Results The T2WI radiomic-clinical nomogram achieved a favorable prediction performance in the training and validation cohort with an area under ROC curve (AUC) of 0.866 and 0.818, respectively. The DCA showed that the T2WI radiomic-clinical nomogram was better than other models with a greater clinical net benefit. Conclusion MR-based radiomics analysis showed the high accuracy in prognostic estimation of EOC patients and could help to predict therapeutic outcome before treatment.

PD-L1 Expression in Different Segments and Histological Types of Ovarian Cancer According to Lymphocytic Infiltrate

Background and Objectives: Ovarian cancer is the leading cause of death among gynecological tumors. PD-1/PD-L1 immunoregulatory mechanism is activated in ovarian cancers. Lymphocyte infiltration is a significant factor that affects its expression. We analyzed the correlation between localization of lymphocytic infiltrate and PD-L1 expression in epithelial ovarian tumors. Materials and Methods: PD-L1 expression was analyzed in 328 subjects, 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. Expression in central and invasive tumor parts in epithelial ovarian carcinoma was combined with the most pronounced lymphocyte reaction. Immunohistochemical analysis was performed using the tissue microarray and correlated with a set of histopathology parameters. Results: PD-L1 expression was most prominent in epithelial ovarian carcinoma with different levels of expression observed between invasive and central tumor segments. A high level of PD-L1 expression on tumor cells was more frequently present in the invasive than in the central tumor parts (p < 0.001) only in high-grade serous ovarian carcinoma (HGSC). There was no significant correlation between peritumoral lymphocytic infiltrate and PD-L1 expression regardless of tumor segment. In the central tumor parts of HGSC, there was a correlation of intratumoral lymphocytic infiltrate with a higher level of PD-L1 expression (p = 0.003). Conclusions: The most prominent PD-L1 expression was observed in the invasive tumor parts of HGSC. Only the central parts of the HGSC exhibited significant PD-L1 expression in association with considerable intratumoral lymphocytic infiltrate.

LYVE1+ macrophages of murine peritoneal mesothelium promote omentum-independent ovarian tumor growth

Two resident macrophage subsets reside in peritoneal fluid. Macrophages also reside within mesothelial membranes lining the peritoneal cavity, but they remain poorly characterized. Here, we identified two macrophage populations (LYVE1hi MHC IIlo-hi CX3CR1gfplo/− and LYVE1lo/− MHC IIhi CX3CR1gfphi subsets) in the mesenteric and parietal mesothelial linings of the peritoneum. These macrophages resembled LYVE1+ macrophages within surface membranes of numerous organs. Fate-mapping approaches and analysis of newborn mice showed that LYVE1hi macrophages predominantly originated from embryonic-derived progenitors and were controlled by CSF1 made by Wt1+ stromal cells. Their gene expression profile closely overlapped with ovarian tumor-associated macrophages previously described in the omentum. Indeed, syngeneic epithelial ovarian tumor growth was strongly reduced following in vivo ablation of LYVE1hi macrophages, including in mice that received omentectomy to dissociate the role from omental macrophages. These data reveal that the peritoneal compartment contains at least four resident macrophage populations and that LYVE1hi mesothelial macrophages drive tumor growth independently of the omentum.

Serous Epithelial Ovarian Cancer: Retrospective Analysis of 260 Cases

Objective: To evaluate the outcomes of patients who were followed up and treated for serous epithelial ovarian tumor. Materials and Methods: This retrospective study included 260 patients who were diagnosed with serous epithelial ovarian cancer, treated and followed up at Kanuni Sultan Suleyman Training and Research Hospital between January 2002 and December 2019. Results: The mean age of the patients participated in the study was 53.4±11.6 years. Of the patients, 79.7% had advance stage and 82.4% had grade 3 tumors. The rate of complete or optimal surgery was 88.2%, while the rate of suboptimal surgery was 11.2%. While 82% of the patients received adjuvant chemotherapy, 15.7% received neoadjuvant chemotherapy. Of the patients, 80.2% had a Ca 125 value higher than 35. Despite primary cytoreductive surgery and platinum-based adjuvant chemotherapy, the recurrence rate was 66.2%, and the PFS and OS rates were 34.7±41.0 and 50.5±40.0 months, respectively. Conclusion: The majority of serous epithelial ovarian cancers are diagnosed at an advanced stage. Despite primary situ reductive surgery and subsequent platinum-based chemotherapy, the recurrence rates are quite high.

The Accuracy of Intraoperative Frozen Sections in Epithelial Ovarian Tumor

Objective: To evaluate the accuracy of the intraoperative frozen section in the diagnosis of epithelial ovarian tumor. Materials and Methods: An observational study of epithelial ovarian tumor reports from patients that underwent surgery with intraoperative consultation at Ramathibodi Hospital, Thailand between 2013 and 2017 was done. The frozen section diagnoses were compared with the final surgical diagnoses and the overall accuracy, sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) were studied. Results: One hundred sixteen ovarian specimen reports were reviewed, comprised of 74 (63.8%) benign, 21 (18.1%) borderline, and 21 (18.1%) malignant neoplasms. Nine cases (7.7%) were discordant diagnoses. The overall accuracy was 92.2%. The sensitivity and specificity for benign, borderline, and malignant neoplasms were 100%, 80.9%, and 76.2%, and 88.1%, 95.8%, and 100%, respectively. The PPV and NPV for benign, borderline, and malignant neoplasms were 93.7%, 80.9%, and 100%, and 100%, 95.8%, and 95.0%, respectively. Conclusion: The intraoperative frozen section has high accuracy in the diagnosis of ovarian epithelial neoplasm. The results can be used in guidance on the extent and type of surgical management. Keywords: Frozen section, Accuracy, Epithelial ovarian tumor

Expression of CD133 and Aldehyde Dehydrogenase 1A1 in Borderline Ovarian Tumor and Their Correlation with International Federation of Gynecology and Obstetrics

BACKGROUND: Borderline ovarian tumor (BOT) is an epithelial ovarian tumor with atypical epithelial proliferation without stromal invasion. BOTs may have an aggressive fashion with associated microinvasion feature, peritoneal “implants,” regional lymphadenopathy, and higher International Federation of Gynecology and Obstetrics (FIGO) stage. CD133 is cancer stem cells (CSCs) marker that promotes cell proliferation and tumor invasion through induction of nuclear factor kappa B and upregulation of MMP9. Aldehyde dehydrogenase 1A1 (ALDH1A1) is CSCs marker that promotes cell proliferation through the upregulation of c-MYC and cyclin-D1. AIM: The aim of this study was to investigate the correlation between CD133 and ALDH1A1 expression with FIGO stage. This research was performed as an analytic-observational with a cross-sectional design. METHODS: This research using a paraffin block of patients diagnosed as BOT in Hasan Sadikin Hospital Bandung. Samples were divided in two groups: FIGO stage IA and FIGO stage >IA. All samples were stained by immunohistochemistry CD133 and ALDH1A1. All data were analyzed using the Chi-square test with a significant level 5%. RESULTS: This study showed a statistically significant correlation between CD133 (p = 0.047) and ALDH1A1 (p = 0.042) expression with FIGO stage in BOT. Multivariate analysis showed there was no correlation between CD133 and ALDH1A1 in the affected of FIGO stage in BOT. CONCLUSION: CD133 and ALDH1A1 in BOT can be considered as a factor to predict the prognosis of BOT through predict FIGO stage.

Long-term multidisciplinary integrative therapy management resulted in favorable outcomes for ovarian cancer during pregnancy: a case report and literature review

Background Ovarian cancer during pregnancy is relatively rare and treatment strategies are inexperienced in surgery and chemotherapy. Multidisciplinary management of advanced epithelial ovarian cancer in pregnant patients with strong desire of fertility including sufficient mental and medical understanding, perioperative consideration, intraoperative decision, chemotherapy sensitivity and follow-up after treatment can gain successful outcomes for both maternal disease and fetus’s development. Case presentation A 34-year-old primigravidae was diagnosed with advanced epithelial ovarian tumor and then first cytoreductive surgery to resect macroscopical lesions and protect the uterus for fetus was performed following with four chemotherapy courses (docetaxel and carboplatin) before delivery and four other chemotherapy courses after delivery. Chemotherapy drugs were decided by sensitivity test and the patient’s anaphylaxis. Second surgery involved cesarean section with a healthy offspring and secondary cytoreductive surgery. Operative strategies were considered to gain a balance of disease and risk for fetus. Psychosocial support was provided during the course of diagnosis and treatment for a healthy coping situation. This patient relapsed 19 months after the last chemotherapy course and was treated by additional adjuvant therapy to a clinical remission. The 33-month baby boy has no evidence with disease until now. The follow-up of both mother and baby is still continuing. Conclusions Ovarian cancer during pregnancy has low incidence which must increase in future as women delay reproduction age. Ovarian cancer cytoreductive surgery and chemotherapy have limitation to handle conditions under a desire of fetus protection. Multidisciplinary treatment model is a therapeutic solution and a challenge for gynecological surgeons, medical oncologists, pathologists, obstetricians, neonatologists, pharmacists, anesthetist, and psychologists.

CA125, YKL-40, HE-4 and Mesothelin: a new serum biomarker combination in discrimination of benign and malign epithelial ovarian tumor

Objective Cancer Antigen 125 (CA125) and Risk of Ovarian Malignancy Algorithm (ROMA) score are used for classification of ovarian masses (benign/malign) in preoperative stage. However, their discrimination capacity are considered insufficient, and greatly effected by histological subtype and menopausal status. This study aimed to investigate diagnostic performance of Human epididymis protein 4 (HE4), Y (tyrosine), K (lysine), and L (leucine)-40 (YKL-40), Mesothelin, Rho GDP dissociation inhibitor ß (LyGDI), CA125 or their combinations in discrimination of benign/malign ovarian diseases in preoperative stage. Materials and methods The study groups were comprised sera of 31 epithelial ovarian cancer (EOC), 30 benign ovarian tumor patients, and 32 healthy women. The diagnostic performance of the biomarkers were evaluated based on ROC-AUC values and logistic regression analysis incorporating menopausal status and clinical diagnosis of the subjects. Results Our data demonstrates that “CA125-HE4-Mesothelin-YKL-40” had the highest sensitivity at 80%, 90%, 95% specificity 96.8%, 93.6%, 93.6%, respectively. Conclusion This study provides the first evidence for the combinational uses of “CA125-HE4-Mesothelin-YKL-40” as a panel in distinguishing malign from benign ovarian tumor, not affected by menopausal status unlike ROMA. However, higher patient number may also provide the evaluation of this panel in malign group in terms of tumor stages.