Quality of life among borderline ovarian tumor survivors: A comparison with survivors of early-stage ovarian cancer and a cancer-free population: A cross-sectional population-based PROFILES study.

OBJECTIVE: This study assessed the health-related quality of life (HRQo) of women surviving a borderline ovarian tumor (BOT) in comparison with early-stage ovarian cancer survivors treated surgically alone and with a matched cancer-free population. METHODS: Survivors of BOT and ovarian cancer were invited in two Dutch cross-sectional, population-based studies. Ovarian cancer survivors with tumor stage I who were treated surgically only were included. A random sample from the cancer-free population was matched on sex, age and education to the sample of BOT survivors. The EORTC QLQ-C30 (version 3.0) and the EORTC QLQ-OV28 were completed by the cancer-free population and the BOT and ovarian cancer survivors in study 1 and 2. The Hospital Anxiety and Depression Scale (HADS) was only completed by the cancer-free population and the survivors of BOT and ovarian cancer in study 1. BOT survivors were compared to early-stage ovarian cancer survivors and the general population using linear regression analyses and effect sizes regarding clinical importance. RESULTS: 83 BOT (42%), 88 early-stage ovarian cancer survivors (52%), and 82 women from the general population were included. In most HRQoL domains, BOT survivors were not significantly different from early-stage ovarian cancer survivors and the cancer-free population, except that BOT survivors reported significantly less insomnia than early-stage ovarian cancer survivors and more dyspnea than the cancer-free population (small clinical difference). CONCLUSION: In general, BOT survivors' HRQoL lies between the HRQoL of early-stage ovarian cancer survivors and of the cancer-free population, but clinical effect sizes between the groups were mostly only trivial.

A Rare Case of Postmenopausal Hirsutism Associated With a Serous Cystadenofibroma of the Ovary.

Hirsutism in females is most commonly associated with polycystic ovarian syndrome, but can also result from congenital adrenal hyperplasia and ovarian tumors like granulosa cell tumors, Sertoli-Leydig cell tumors, and hilus cell tumors. We present a case of a 54-year-old female with hirsutism, diagnosed with ovarian cystadenofibroma. She had a history of premature ovarian failure at the age of 35 and presented with new onset chin and upper lip hair, and scalp hair loss. Labs showed elevated total testosterone, normal dehydroepiandrosterone (DHEA) and sex hormone-binding globulin (SHBG), low estradiol, and postmenopausal range anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Cytogenetic testing showed a normal XX karyotype. Initial transvaginal ultrasound revealed a thickened endometrial stripe and unremarkable ovaries. Repeat ultrasound and MRI noted persistent endometrial thickening and a solid-cystic structure in the left ovary. The patient underwent total hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node dissection. Endometrial biopsy showed FIGO grade 1 endometrioid carcinoma, and the left ovary biopsy revealed benign serous cystadenofibroma and endometriosis. Postoperatively, hirsutism resolved and testosterone levels normalized. Hirsutism in postmenopausal women should prompt evaluation for adrenal or ovarian sources, including tumors. Ovarian tumors cause about 1% of hirsutism cases. Our case highlights the need for thorough evaluation, as benign ovarian tumors can also cause androgen excess and associated conditions like endometrial cancer.

Gastrointestinal Stromal Tumors (GISTs) Mimicking Primary Ovarian Tumors or Metastasizing to the Ovaries: A Systematic Literature Review.

Background: Gastrointestinal stromal tumors (GISTs) are a rare neoplasm, sometimes mimicking primary ovarian tumors (OTs) and/or metastasizing to the ovaries (M-OT). We performed a systematic literature review (SLR) of OTs and M-OTs, investigating differences in recurrence-free and overall survival. Methods: Our SLR was performed according to PRISMA guidelines, searching in Pubmed, Scopus, and Web of Science databases from inception until 21 April 2024. Results: Overall, 59 OTs (Group 1) and 21 M-OTs (Group 2) were retrieved. The absence of residual disease after surgery was achieved significantly in a higher percentage of patients with Group 1 GISTs (91.5%) compared with Group 2 GISTs (57.1%). Chemotherapy was more frequently administered to Group 2 patients (33% vs. 0%). Recurrence and deaths for disease were significantly more frequent in Group 2 than Group 1 cases (54.5% vs. 6.8%, and 37.5% vs. 9.8%, respectively). Conclusions: GISTs can rarely mimic primary ovarian cancers or even more rarely metastasize to the ovaries. Group 1 GISTs occurred in younger women, were not associated with elevated tumor markers, and had a better prognosis. In contrast, Group 2 GISTs occurred in older women, may exhibit elevated tumor markers, and presented a worse prognosis. However, no significant statistical difference for survival between the two studied groups was detected. Computed tomography scans can define the size of GISTs, which correlate to stage and prognostic risk classes. The gold standard treatment is complete surgical resection, which was achieved in almost all cases of Group 1 GISTs and in half of Group 2. Histopathology and immunohistochemistry are essential for the final diagnosis and guide chemotherapy treatment.

A Case Report of Comprehensive Diagnostic Approach on a Complex Left Adnexal Mass in a Young Female: Endometrioma or Complicated Ovarian Serous Cystadenofibroma.

This case report presents a young female who was clinically, radiologically, and intraoperatively misdiagnosed as an ovarian endometrioma and was only diagnosed by histopathological biopsy as complicated serous cystadenofibroma, a rare benign tumor composed of both glandular and fibrous tissue. The diagnosis of adenofibroma typically involves a combination of imaging studies, such as ultrasound or magnetic resonance imaging (MRI) scan, and a histopathological biopsy to confirm the presence of the tumor. This case underscores the significance of utilizing various diagnostic methods and histopathological biopsies to diagnose and treat complex adnexal masses in females accurately.

Nomogram development for predicting ovarian tumor malignancy using inflammatory biomarker and CA-125.

Global challenges in ovarian cancer underscore the need for cost-effective screening. This study aims to assess the role of pretreatment Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte-Ratio (LMR), Platelet-to-Lymphocyte Ratio (PLR), and CA-125 in distinguishing benign and malignant ovarian tumors, while also constructing nomogram models for distinguish benign and malignant ovarian tumor using inflammatory biomarkers and CA-125. This is a retrospective study of 206 ovarian tumor patients. We conducted bivariate analysis to compare mean values of CA-125, LMR, NLR, and PLR with histopathology results. Multiple regression logistic analysis was then employed to establish predictive models for malignancy. NLR, PLR, and CA-125 exhibited statistically higher levels in malignant ovarian tumors compared to benign ones (5.56 ± 4.8 vs. 2.9 ± 2.58, 278.12 ± 165.2 vs. 180.64 ± 89.95, 537.2 ± 1621.47 vs. 110.08 ± 393.05, respectively), while lower LMR was associated with malignant tumors compared to benign (3.2 ± 1.6 vs. 4.24 ± 1.78, p = 0.0001). Multiple logistic regression analysis revealed that both PLR and CA125 emerged as independent risk factors for malignancy in ovarian tumors (P(z) 0.03 and 0.01, respectively). Utilizing the outcomes of multiple regression logistic analysis, a nomogram was constructed to enhance malignancy prediction in ovarian tumors. In conclusion, our study emphasizes the significance of NLR, PLR, CA-125, and LMR in diagnosing ovarian tumors. PLR and CA-125 emerged as independent risk factors for distinguishing between benign and malignant tumors. The nomogram model offers a practical way to enhance diagnostic precision.

Health-related quality of life, sexual function, psychological health, reproductive concerns and fertility outcome in young women treated with fertility-sparing surgery for ovarian tumors - A prospective longitudinal multicentre study.

OBJECTIVE: This study aimed to investigate health-related quality of life (HRQoL), sexual function, psychological-health, reproductive concerns, and fertility outcomes of women of reproductive age undergoing Fertility-Sparing Surgery (FSS) for treatment of ovarian cancer (OC) or borderline ovarian tumor (BOT), over a 2-year period. METHODS: Prospective longitudinal multicentre study including women 18-40 years undergoing FSS between 2016 and 2018 in Sweden. Clinical data at diagnosis, histopathological findings and 2-year follow-up regarding oncological and reproductive outcomes were collected. Participants completed the EORTC QLQ-C30 and OV-28, FSFI, HADS and study-specific items at time of diagnosis and at one- and two-years following FSS. Data were analysed using a model for repeated measures to investigate changes over time. RESULTS: Of 68 eligible women, 49 were included following exclusions due to benign pathology or subsequent radical surgery. During a mean follow-up of 20.5 months, two women experienced a recurrence and 82% reported regular menstruations. The majority (94%) had a strong desire to become biological mothers, which remained or increased over time. The conception-rate was 76%. HRQoL, psychological-health and sexual function improved over time and the proportion of women with sexual dysfunction decreased. At one-year follow-up 50% of nulliparous women had scores indicating sexual dysfunction compared to 0% of the women who had given birth either before or after surgery (p = 0.008). CONCLUSION: HRQoL, psychological-health and sexual function improved during two-year follow-up after FSS in young women presenting with OC or BOT. Women who had given birth prior to or after FSS reported improved sexual function compared to nulliparous women.

Minimally invasive and robotic-assisted approaches applied to pediatric surgical oncology.

The management of pediatric tumors is complex, with surgery, chemotherapy, and radiotherapy being cornerstones in their treatment. Tumor removal is increasingly performed by a minimally invasive approach, which allows for quicker postoperative recovery and less postoperative pain. The goal of this report is to give an overview of minimally invasive surgical approaches for common pediatric tumors, with a focus on technical considerations and postoperative outcomes.

Case report: A huge retroperitoneal solitary fibrous tumor closely related to the external iliac vessels misdiagnosed as an ovarian tumor.

Background: Solitary fibrous tumor (SFT) is a rare soft tissue tumor originating from mesenchymal cells. Thus far, there have been no reported cases of SFT closely related to the iliac vessels. Case presentation: An elderly woman was found to have had a lower abdominal mass for more than 20 years. The enhanced computerized tomography (CT) showed a progressively enhanced hypervascular mass. The external iliac blood vessels were closely related to the mass, which was misdiagnosed as an ovarian tumor. During laparotomy, the external iliac vein was seen to penetrate the tumor, and the external iliac artery was seen to penetrate the tumor capsule. The retroperitoneal tumor was diagnosed during the operation. The surgical plan of complete tumor resection, severing of the external iliac arteries and veins, and blood vessel replacement was implemented. Pathological immunohistochemistry showed positive results for STAT6 and CD34, confirming the diagnosis of giant retroperitoneal SFT. The risk is classified as high and requires long-term follow-up. There has been no local recurrence or distant metastasis almost 1 year after surgery. Conclusion: The incidence of giant retroperitoneal SFT is rare, and the diagnosis can be confirmed through preoperative imaging examination and pathological examination. If the SFT capsule is intact, there is a chance of surgical resection. For SFTs that are penetrated by the iliac blood vessels, adequate preparation must be made before the surgery is performed. Removing the tumor and the iliac blood vessels at the corresponding site and then replacing it with artificial blood vessels is a feasible method with less risk of bleeding. In this case, imaging showed a progressively enhancing hypervascular mass in the lower abdomen, which was related to blood vessels. Preoperative biopsy and pathological testing can confirm the diagnosis. Neoadjuvant therapy or interventional therapy before surgery can shrink the tumor, making the surgical procedure relatively easy with less risk of bleeding.

An extensive immunohistochemical analysis of 290 ovarian adult granulosa cell tumors with 29 markers.

The current knowledge about the immunohistochemical features of adult granulosa cell tumor (AGCT) is mostly limited to the "traditional" immunohistochemical markers of sex cord differentiation, such as inhibin, calretinin, FOXL2, SF1, and CD99. Knowledge about the immunohistochemical markers possibly used for predictive purpose is limited. In our study, we focused on the immunohistochemical examination of 290 cases of AGCT classified based on strict diagnostic criteria, including molecular testing. The antibodies used included 12 of the "diagnostic" antibodies already examined in previous studies, 10 antibodies whose expression has not yet been examined in AGCT, and 7 antibodies with possible predictive significance, including the expression of HER2, PD-L1, CTLA4, and 4 mismatch repair (MMR) proteins. The results of our study showed expression of FOXL2, SF1, CD99, inhibin A, calretinin, ER, PR, AR, CKAE1/3, and CAIX in 98%, 100%, 90%, 78%, 45%, 41%, 94%, 82%, 26%, and 9% of AGCT, respectively. GATA3, SATB2, napsin A, MUC4, TTF1, and CD44 were all negative. PTEN showed a loss of expression in 71% of cases and DPC4 in 4% of cases. The aberrant staining pattern (overexpression) of p53 was found in 1% (3/268) of cases, 2 primary tumors, and 1 recurrent case. Concerning the predictive markers, the results of our study showed that AGCT is microsatellite stable, do not express PD-L1, and are HER2 negative. The CTLA4 expression was found in almost 70% of AGCT tumor cells.

Incidentally Discovered Giant Benign Ovarian Serous Cystadenoma in Elective Bariatric Surgery.

Ovarian cystadenomas are benign epithelial neoplasms, many of which are of the serous subtype. Most patients present with symptoms such as abdominal pain, bloating, and bladder issues. This patient, who had a BMI of 45, presented with a giant ovarian serous cystadenoma identified during an elective bariatric surgery; interestingly, she was completely asymptomatic at the time of discovery. A large, predominantly cystic pelvic mass with internal septations and soft tissue components, suspicious for ovarian neoplasm, was discovered on a CT abdomen and pelvis with IV contrast. She underwent an exploratory laparotomy with complete resection, right oophorectomy, and ovarian cystectomy. Her postoperative pathology report revealed the mass to be a benign serous cystadenoma. This case serves as an example of how a massive tumor can potentially get overlooked for many years, only to be detected unintentionally in an asymptomatic patient. Healthcare quality is often negatively impacted by the inherent prejudice that many healthcare providers have toward their obese patients. Providers may mistakenly over-attribute a patient's symptoms to their obesity, failing to effectively evaluate the patient's concerns, which could lead to overlooking potentially harmful diagnoses. A comprehensive history and physical exam in all patients, especially those who are obese, is vital in ensuring timely diagnosis and management to improve patient outcomes.

Factors Affecting the Diagnostic Discordance Between Frozen and Permanent Sections in Mucinous Ovarian Tumors.

Purpose: To investigate the accuracy of intraoperative frozen section (FS) diagnosis for predicting the permanent section (PS) diagnosis of mucinous ovarian tumors and evaluate the factors affecting the diagnostic discordance. Patients and Methods: This retrospective cohort study was performed in Tianjin Medical University General Hospital. All women who underwent ovarian surgery with FS between January 2011 and December 2022 were identified, and those with a diagnosis of mucinous ovarian tumor (MOT) by FS or PS were reviewed. Clinical and pathologic data were extracted. Results: A total of 180 women were included, of which 141 (78.33%) had diagnostic concordance between FS and PS, yielding a sensitivity of 83.43% and a positive predictive value (PPV) of 92.76%. Under- and over-diagnosis occurred in 28 cases (15.56%) and 11 cases (6.11%). Tumor size > 13cm (OR 3.79, 95% CI 1.12-12.73) was an independent risk factor for under-diagnosis, and tumor size ≤ 13cm (OR 16.78, 95% CI 0.01-0.49), laparoscopic surgery (OR 0.14, 95% CI 0.02-0.92), the combination of other tumor components (including serous, Brenner tumor, and chocolate cyst; OR 7.00, 95% CI 1.19-41.12) were independently associated with over-diagnosis. The Kaplan-Meier survival curves and the Log rank test showed no significant difference between misdiagnosed and accurately diagnosed patients (all P > 0.05). Conclusion: Intraoperative frozen pathology of MOT is problematic for under- and over-diagnosis. The incorrect diagnosis of FS was related to determining the extent of surgery but had no impact on the patients' long-term recurrence and survival outcomes. In future clinical practice, surgeons need to obtain material accurately and enhance communication with pathologists during the operation to improve the accuracy of FS diagnosis.

Radiomics analysis of ultrasound images to discriminate between benign and malignant adnexal masses with solid ultrasound morphology.

OBJECTIVE: Our primary aim was to identify radiomic ultrasound features that can distinguish benign from malignant adnexal masses with solid ultrasound morphology, and primary invasive from metastatic solid ovarian masses, and to develop ultrasound-based machine learning models that include radiomics features to discriminate between benign and malignant solid adnexal masses. Our secondary aim was to compare the diagnostic performance of our radiomics models with that of the ADNEX model and subjective assessment by an experienced ultrasound examiner. METHODS: This is a retrospective observational single center study. Patients with a histological diagnosis of an adnexal tumor with solid morphology at preoperative ultrasound examination performed between 2014 and 2021 were included. The patient cohort was split into training and validation sets with a ratio of 70:30 and with the same proportion of benign and malignant (borderline, primary invasive and metastatic) tumors in the two subsets. The extracted radiomic features belonged to two different families: intensity-based statistical features and textural features. Models to predict malignancy were built based on a random forest classifier, fine-tuned using 5-fold cross-validation over the training set, and tested on the held-out validation set. The variables used in model building were patient's age, and those radiomic features that were statistically significantly different between benign and malignant adnexal masses (Wilcoxon-Mann-Whitney Test with Benjamini-Hochberg correction for multiple comparisons) and assessed as not redundant based on the Pearson correlation coefficient. We describe discriminative ability as area under the receiver operating characteristics curve (AUC) and classification performance as sensitivity and specificity. RESULTS: 326 patients were identified and 775 preoperative ultrasound images were analyzed. 68 radiomic features were extracted, 52 differed statistically significantly between benign and malignant tumors in the training set, and 18 features were selected for inclusion in model building. The same 52 radiomic features differed statistically significantly between benign, primary invasive malignant and metastatic tumors. However, the values of the features manifested overlap between primary malignant and metastatic tumors and did not differ statistically significantly between them. In the validation set, 25/98 tumors (25.5%) were benign, 73/98 (74.5%) were malignant (6 borderline, 57 primary invasive, 10 metastases). In the validation set, a model including only radiomics features had an AUC of 0.80, and 78% sensitivity and 76% specificity at its optimal risk of malignancy cutoff (68% based on Youden's index). The corresponding results for a model including age and radiomics features were 0.79, 86% and 56% (cutoff 60% based on Youden's method), while those of the ADNEX model were 0.88, 99% and 64% (at 20% malignancy cutoff). Subjective assessment had sensitivity 99% and specificity 72%. CONCLUSIONS: Even though our radiomics models had discriminative ability inferior to that of the ADNEX model, our results are promising enough to justify continued development of radiomics analysis of ultrasound images of adnexal masses. This article is protected by copyright. All rights reserved.

I saw the "sea anemone" sign: Puffy face of borderline ovarian tumors.

The sea anemone sign is a radiologic sign seen on magnetic resonance imaging (MRI) studies that indicates the morphological development of serous borderline ovarian tumors (SBOTs), as papillary projections originating from the wall of the cystic lesion. The presence of T2 hypointense fibrous stroma in the center of the papilla is a helpful tip in the diagnosis of SBOTs. Those projections might also be assumed to have a frond-like appearance which can be seen as branching papillary projections, especially on T2-weighted imaging. The term "sea anemone" sign is described by Tanaka et al. who deemed it as a "hallmark" feature of surface SBOTs.

Antidepressant use and ovarian cancer risk: Evidence from nationwide studies with >14,000 cases from Denmark and Sweden.

OBJECTIVE: Given that the evidence regarding the link between antidepressant use and ovarian cancer risk is equivocal, we investigated this research question by conducting two nationwide nested case-control studies among the Danish and Swedish populations. METHODS: Altogether, 14,121 women with epithelial ovarian cancer (30-84 years old) (Denmark: 8976 diagnosed 2000-2019, Sweden: 5145 diagnosed 2010-2018) were randomly age-matched with 564,840 female controls (359,040 from Denmark, and 205,800 from Sweden) using risk set sampling. We used conditional logistic regression to estimate odds ratios (OR) with 95 % confidence intervals (CI) and combined the estimates based on the fixed-effect assumption. We also investigated potential effect modification by well-established risk factors for ovarian cancer. RESULTS: Antidepressant use was associated with an overall reduced risk of ovarian cancer (OR = 0.92, 95%CI: 0.88-0.96), and that reduction was more pronounced in postmenopausal women and long-term users. The effect was most pronounced for serous ovarian tumors (OR = 0.90, 95%CI: 0.86-0.95) but was also observed in other subtypes, although not statistically significant. Among different types of antidepressants, selective serotonin reuptake inhibitors in general and citalopram in particular exhibited a noteworthy reduction in ovarian cancer risk (OR = 0.89, 95%CI: 0.82-0.96). Additionally, use of oral contraceptives and hormone replacement therapy individually modified the association between antidepressant use and ovarian cancer risk. CONCLUSIONS: Use of an antidepressant was associated with a slight, but statistically significant, decrease in ovarian cancer risk. Given the morbidity and mortality associated with ovarian cancer, and increasing use of antidepressants, these findings may be of significance to cancer prevention and should be studied in more detail mechanistically.

Fertility potential and safety assessment of residual ovarian cortex in young women diagnosed with epithelial borderline and early-stage malignant ovarian tumors.

OBJECTIVE: To establish the safety and quality of ovarian cortex surrounding epithelial ovarian tumors in women eligible for fertility-sparing surgery by identifying occult malignant lesions and characterizing the ovarian follicle pool. METHODS: Multicentric retrospective study of 48 subjects (15-45 years), diagnosed with borderline ovarian tumors (BOTs) or early-stage epithelial ovarian cancers (EOCs) and eligible for fertility-sparing surgery. Histological samples of ovarian cortex surrounding tumors were analyzed to characterize the follicle pool, find any occult malignant lesion using tumor-specific markers (cytokeratin 7 and mucin 1), and quantify tumor-infiltrating lymphocytes (TILs) by CD3 and tumor associated macrophages (TAMs) by CD68. RESULTS: Occult ovarian lesions were observed in 6 out of 45 cases investigated (14.6%), including one mucinous stage-I BOT (1/14), one serous stage-I BOT (1/13), 3 advanced-stage serous BOTs (3/11) and one early-stage serous EOC (1/7). Notably, follicle density was significantly lower in subjects diagnosed with ovarian tumors compared to controls (p < 0.001) and at a younger age. Significantly higher follicle atresia was encountered in the ovarian tumor group then in controls (20.1 ± 8.8% vs 9.2 ± 9.4%, p < 0.001) at all ages. Both TILs and TAMs were found in ovarian tumors irrespective of histotype, but no link was established with the status of the ovarian reserve. CONCLUSIONS: Personalized counseling for fertility preservation is required in the event of BOTs and early-stage EOCs. Fertility-sparing surgery and adjuvant gamete preservation should be considered, balancing the oncological risks according to tumor stage and histotype and fertility potential, especially at a younger age.

Impact of Surgical Timing (Primary, Delayed, or Second Look) on Surgical Morbidity and Outcomes in Malignant Germ Cell Tumor of the Ovary in Children.

BACKGROUND: Malignant ovarian germ cell tumors (MOGCT) are rare in children. Surgery with or without chemotherapy is the primary treatment approach. This study aimed to analyze the impact of primary and delayed surgery on surgical morbidity and outcomes. Second-look surgery after inadequate surgical staging and the various components of surgical staging were also evaluated. METHODS: Children below 15 years with MOGCT treated between 2006 and 2022 were analyzed. A comparison of patients undergoing primary, delayed, and second-look surgery was performed. RESULTS: 118 patients with a median age of 12 (0.11-15) years were eligible. Forty patients underwent primary, 51 delayed, and 27 second-look surgeries. Overall complications, including tumor rupture, blood loss, and adjacent organ removal, were significantly higher in the primary compared to the delayed surgery group (p = 0.0001). Second-look surgery conceded more blood loss (p = 0.0001), extended duration (p = 0.03), and complications (p = 0.004) than delayed surgery. The compliance with surgical guidelines was 100% for most components, with a positive yield rate of 10-80%. At a median follow-up of 5.2 years, the 5-year event-free survival (EFS) and overall survival (OS) for the entire cohort are 86% and 89%, respectively. The OS and EFS did not differ by the timing of surgery, although the second-look surgery demonstrated relatively inferior outcomes consequential to initial suboptimal surgery. CONCLUSIONS: MOGCT shows favorable outcomes. Delayed surgery after chemotherapy in appropriately selected patients minimizes the morbidity of surgery with similar outcomes compared to primary surgery. An optimal initial surgery is essential since second-look surgery produces significant morbidity. Prognosis Study, Level II evidence.

A matter of new life and cell death: programmed cell death in the mammalian ovary.

BACKGROUND: The mammalian ovary is a unique organ that displays a distinctive feature of cyclic changes throughout the entire reproductive period. The estrous/menstrual cycles are associated with drastic functional and morphological rearrangements of ovarian tissue, including follicular development and degeneration, and the formation and subsequent atrophy of the corpus luteum. The flawless execution of these reiterative processes is impossible without the involvement of programmed cell death (PCD). MAIN TEXT: PCD is crucial for efficient and careful clearance of excessive, depleted, or obsolete ovarian structures for ovarian cycling. Moreover, PCD facilitates selection of high-quality oocytes and formation of the ovarian reserve during embryonic and juvenile development. Disruption of PCD regulation can heavily impact the ovarian functions and is associated with various pathologies, from a moderate decrease in fertility to severe hormonal disturbance, complete loss of reproductive function, and tumorigenesis. This comprehensive review aims to provide updated information on the role of PCD in various processes occurring in normal and pathologic ovaries. Three major events of PCD in the ovary-progenitor germ cell depletion, follicular atresia, and corpus luteum degradation-are described, alongside the detailed information on molecular regulation of these processes, highlighting the contribution of apoptosis, autophagy, necroptosis, and ferroptosis. Ultimately, the current knowledge of PCD aberrations associated with pathologies, such as polycystic ovarian syndrome, premature ovarian insufficiency, and tumors of ovarian origin, is outlined. CONCLUSION: PCD is an essential element in ovarian development, functions and pathologies. A thorough understanding of molecular mechanisms regulating PCD events is required for future advances in the diagnosis and management of various disorders of the ovary and the female reproductive system in general.

Risk of borderline ovarian tumors after fertility treatment - Results from a Danish cohort of infertile women.

OBJECTIVE: Results from previous studies examining the association between fertility treatment and borderline ovarian tumors are inconsistent. The aim of this study was to investigate the association between fertility treatment and borderline ovarian tumors in a cohort of infertile women. METHODS: This cohort study was based on the Danish Infertility Cohort and included all infertile women aged 20-45 years living in Denmark between 1 January 1995 and 31 December 2017 (n = 146,891). Information on use of fertility drugs, borderline ovarian tumors and cancer diagnoses, covariates, emigration, and vital status was obtained by linkage to national registers. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) with adjustment for potential confounders for overall borderline ovarian tumors and for serous- and mucinous borderline ovarian tumors separately. RESULTS: During a median 11.3 years of follow-up, 144 women developed a borderline ovarian tumor. No marked associations between ever use of clomiphene citrate, gonadotropins, gonadotropin-releasing hormone receptor modulators, human chorionic gonadotropin or progesterone and borderline ovarian tumors were observed, neither overall nor for serous and mucinous borderline ovarian tumors analysed separately. Further, no clear associations with borderline ovarian tumors were found according to cumulative dose, time since first use or parity status for any fertility drugs. CONCLUSIONS: No marked associations between use of fertility drugs and borderline ovarian tumors were observed. However, the cohort's relatively young age at end of follow-up emphasizes the importance of extending the follow-up period for women who have used fertility drugs.

A comprehensive population-based study of malignant ovarian tumors, including histologic and immunohistochemical review, in children and adolescents 0-19 years old in Sweden between 1970 and 2014.

OBJECTIVES: Ovarian tumors in the pediatric population are rare. The incidence and frequency of subtypes differ between children and adults. Although not all tumors are aggressive, they may still lead to morbidity. The goal of this study was a comprehensive review of malignant ovarian tumors in children and adolescents diagnosed and registered in Sweden. METHODS: Individuals were identified through a search in the National Cancer Register, limited for ages 0-19, years 1970-2014. Stored tumor diagnostic material from regional biobanks was retrieved and reviewed. RESULTS: The study includes 345 individuals with ovarian tumors and 70.7% of them were between 15 and 19 years at time of diagnosis. No differences in incidence over time or geographic location were identified. The average follow-up time was 21.2 years and 5-year survival was 88.4%. Survival was similar in the different time periods, except for 1970-1979. Review was possible for 260 cases, resulting in 85 epithelial tumors, 121 GCTs, 47 SCSTs and 7 others. For age 0-4 years SCSTs dominated (85.7%), for 5-9- and 10-14-years GCTs dominated (70,8% and 75.0% respectively), and for age 15-19 years epithelial tumors dominated (43.8%). There was a strong agreement between review diagnosis and original diagnosis (Cohen's κ 0.944). Differentiating between entities within the sex cord-stromal group posed the biggest diagnostic challenge. CONCLUSIONS: Ovarian tumors in children and adolescents are rare and distinct from their adult counterparts regarding incidence and frequency. There was a strong concurrence between original and review diagnoses. The greatest diagnostic difficulty was subtyping of epithelial tumors and differentiating between tumors within the SCST group.

CT-Based Radiomics and Machine Learning for Differentiating Benign, Borderline, and Early-Stage Malignant Ovarian Tumors.

To explore the value of CT-based radiomics model in the differential diagnosis of benign ovarian tumors (BeOTs), borderline ovarian tumors (BOTs), and early malignant ovarian tumors (eMOTs). The retrospective research was conducted with pathologically confirmed 258 ovarian tumor patients from January 2014 to February 2021. The patients were randomly allocated to a training cohort (n = 198) and a test cohort (n = 60). By providing a three-dimensional (3D) characterization of the volume of interest (VOI) at the maximum level of images, 4238 radiomic features were extracted from the VOI per patient. The Wilcoxon-Mann-Whitney (WMW) test, least absolute shrinkage and selection operator (LASSO), and support vector machine (SVM) were employed to select the radiomic features. Five machine learning (ML) algorithms were applied to construct three-class diagnostic models. Leave-one-out cross-validation (LOOCV) was implemented to evaluate the performance of the radiomics models. The test cohort was used to verify the generalization ability of the radiomics models. The receiver-operating characteristic (ROC) was used to evaluate diagnostic performance of radiomics model. Global and discrimination performance of five models was evaluated by average area under the ROC curve (AUC). The average ROC indicated that random forest (RF) diagnostic model in training cohort demonstrated the best diagnostic performance (micro/macro average AUC, 0.98/0.99), which was then confirmed with by LOOCV (micro/macro average AUC, 0.89/0.88) and external validation (test cohort) (micro/macro average AUC, 0.81/0.79). Our proposed CT-based radiomics diagnostic models may effectively assist in preoperatively differentiating BeOTs, BOTs, and eMOTs.