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.

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.

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.

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.

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.

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.

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.

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.

Ultrasonographic diagnosis of adnexal masses: interobserver agreement in the interpretation of videos, using IOTA terminology.

OBJECTIVES: Aim of this study is to estimate interobserver agreement in classifying adnexal tumors using IOTA terms, simple rules and subjective assessment. In addition, we related observers' accuracy with their experience in gynecological ultrasonography and the year of IOTA certification. METHODS: Eleven observers with three different levels of experience evaluated videoclips of 70 adnexal masses, defining tumor type according to IOTA terms and definitions, classifying the mass using IOTA Simple rules and Subjective assessment as well as providing Color Score evaluation. Sensitivity, specificity and area under the ROC curve were calculated and the year of IOTA certification was related with operators' accuracy through Pearson correlation coefficient. Interobserver agreement was estimated calculating percentage of agreement, Fleiss kappa and Cohen's kappa. RESULTS: We found a positive correlation between the year of IOTA certification and operators' accuracy (Pearson coefficient 0.694), especially among the observers with the least experience, the residents (p = 0.003). For tumor type classification, identification of papillary projections and classification of tumors using subjective assessment, agreement among all observers was moderate (Fleiss kappa 0.455, 0.552, and 0.476, respectively) and increased with the years of experience. Agreement in the application of Simple Rules was moderate in all examiners with IOTA certification, with Fleiss kappa in the range of (0.403, 0.498). For Color Score assignment interobserver agreement among all observers was fair (Cohen's kappa 0.380). CONCLUSIONS: Even among expert examiners, the results of adnexal lesion assessment can be inconsistent. Experience impacts on accuracy and agreement in subjective assessment, while the application of Simple Rules can mitigate the role of experience in interobserver agreement. The knowledge of IOTA models among residents seams to improve their diagnostic accuracy, showing the benefits of IOTA terminology for in training sonographers.

Does controlled ovarian hyperstimulation in women with a history of borderline tumor influence recurrence rate?

PURPOSE: To determine the recurrence rate in the women with controlled ovarian hyperstimulation after a history of borderline ovarian tumors (BOT). METHODS: This was a retrospective analysis of 275 patients with BOT undergoing surgery for fertility preservation in our hospital between 2001 and 2017. Cases were divided into an assisted reproductive technology (ART) treatment group (n = 15) and a non-ART treatment group (n = 260). We compared the recurrence rate, survival rate and pregnancy outcomes between these two groups. RESULTS: The ART group had a higher recurrence rate (33.33% vs. 10.80%, P = 0.023). Survival analysis indicated that the recurrence time in patients undergoing ART was significantly shorter (P = 0.026). A low pregnancy rate before diagnosis, and high intraoperative blood loss, were associated with postoperative ART treatment (P < 0.05). Multivariate analysis showed that ART treatment and bilateral lesions both significantly increased the risk of recurrence (P < 0.05). The pathological type of recurrent tumors was often the same as the initial tumor. CONCLUSION: The postoperative use of ART in patients with BOT significantly increased the recurrence rate, but does not significantly affect the overall survival rate of patients. Therefore, ART in such patients should be individualized, and close follow-up is necessary after ART.

Risk of epithelial ovarian tumors among women with polycystic ovary syndrome: A nationwide population-based cohort study.

An association between polycystic ovary syndrome (PCOS) and epithelial ovarian tumors is biologically plausible as conditions inherent to PCOS such as excessive androgenic hormones, reproductive factors and obesity are also risk factors for these hormone-sensitive tumors. However, previous studies have showed conflicting results and have various methodological limitations. This population-based cohort study investigates the association between PCOS and epithelial ovarian tumors and includes all women born in Denmark between January 1, 1940 and December 31, 1993 (n = 1 719 304). PCOS diagnoses, ovarian cancer and borderline ovarian tumor diagnoses, covariates, migration and vital status were obtained from the Danish national registers. Adjusted cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for epithelial ovarian cancer and for borderline ovarian tumors overall as well as for histological subtypes separately. During median 26 years of follow-up we identified 6490 women with ovarian cancer and 2990 women with borderline ovarian tumors. Overall, we observed no marked associations between a diagnosis of PCOS and overall epithelial ovarian cancer or overall epithelial borderline ovarian tumors, irrespective of time since diagnosis. However, we found an increased risk of ovarian cancer among postmenopausal women with PCOS (HR 2.28 95% CI 1.02-5.09) and an increased risk of serous borderline ovarian tumors (HR 2.34 95% CI 1.21-4.53) in women with PCOS compared with women without PCOS. Importantly, low statistical precision is a crucial limitation of our study and in previous studies and larger studies with longer follow-up are therefore warranted.

Risk of nonovarian cancer in a nationwide-based study of nearly 5000 women with borderline ovarian tumors in Denmark.

Evidence regarding cancer risk after borderline ovarian tumors (BOTs) is limited. We conducted a nationwide cohort study examining the incidence of nonovarian cancers in women with serous or mucinous BOTs compared with the general female population with up to 41 years of follow-up. Through the nationwide Pathology Registry, we identified nearly 5000 women with BOTs (2506 serous and 2493 mucinous) in Denmark, 1978 to 2018. We computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as relative risk estimates of specific nonovarian cancers. Compared with general female population rates, women with serous BOTs had increased rates of particularly malignant melanoma (SIR = 1.9; 95% CI: 1.3-2.6), thyroid cancer (SIR = 3.0; 95% CI: 1.4-5.4) and myeloid leukemia (SIR = 3.2; 95% CI: 1.5-5.8), and women with mucinous BOTs had elevated rates of lung cancer (SIR = 1.7; 95% CI: 1.3-2.1), pancreatic cancer (SIR = 1.9; 95% CI: 1.2-2.9) and myeloid leukemia (SIR = 2.3; 95% CI: 0.9-4.7). We found no convincing association with neither breast nor colorectal cancer in women with BOTs. This is the first large nationwide study showing that women with specific types of BOTs have increased risks of several nonovarian cancers, likely due to some shared risk factors or genetic characteristics.

Bractoppin, a BRCA1 carboxy-terminal domain (BRCT) inhibitor, suppresses tumor progression in ovarian borderline tumor organoids.

Borderline ovarian tumors are a special class of ovarian tumors between benign and malignant, which are not sensitive to traditional chemotherapy regimens, and the development of target drugs is limited due to the lack of cell lines. Tumor organoids can well preserve the genetic characteristics of the primary tumor, but there are only a few reports of application in borderline tumors. In this study, we successfully generated 13 ovarian borderline tumor organoids and tested the antitumor activity of Bractoppin, a BRCA1 carboxy-terminal domain (BRCT) inhibitor. Bractoppin promotes organoid apoptosis. Mechanistically, Bractoppin can inhibit organoid cell cycle progression, inhibit the repair of DSB damage and promote tumor cell apoptosis. In addition, Bractoppin can also promote the apoptosis of ovarian cancer cell lines and inhibit the HR and NHEJ repair ability of tumor cells. We demonstrate the value of ovarian borderline tumor organoids in the exploration of molecular therapy drugs, and Bractoppin may be a valuable small molecule drug in the treatment of BOT.

Risks of non-ovarian cancers in women with borderline ovarian tumor: a national cohort study in Sweden.

BACKGROUND: Associations between different cancer types are known. The affirmation of the risk for non-ovarian cancer after ovarian borderline tumors (BOT) is, however, sparse. AIM: To analyze the risk of subsequent or simultaneous cancers in women with BOTs compared with the general female Swedish population. METHODS: An open cohort study (1995-2018) was conducted where a diagnosis of BOTs as well as subsequent or simultaneous cancer diagnoses were obtained from the Swedish Cancer Register and matched to the Total Population Register. Each woman with BOT was followed until non-ovarian cancer, death or emigration and could only be included once for the outcome. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for specific non-ovarian cancers were analyzed. RESULTS: The 4998 women with serous and mucinous BOTs were diagnosed during 1995-2018 with a mean age of 55.7 years (SD 16.0) at diagnosis. Compared with the general female population, women with BOTs had increased risks for non-ovarian cancer in colon (SIR = 2.5; 95% CI 2.0-3.1), rectum (SIR = 1.7; 95% CI 1.1-2.5), small intestine (SIR = 5.0; 95% CI 2.3-9.5), cervix (SIR = 2.5; 95% CI 1.4-4.2), endometrium (SIR = 2.4; 95% CI 1.9-3.1), pancreas (SIR = 2.3; 95% CI 1.4-3.5), upper aerodigestive tract (SIR = 2.2; 95% CI 1.2-3.8), lung (SIR = 1.8; 95% CI 1.4-2.3), kidney (SIR = 2.3; 95% CI 1.4-3.7) and bladder (SIR = 1.8; 95% CI 1.1-2.8). Among women with serous BOTs, the risk of thyroid gland cancer (SIR = 3.1; 95% CI 1.2-6.4) was also increased. Lung and pancreas cancer showed increased risks more than 1 year after a diagnosis of BOT. CONCLUSIONS: This Swedish population-based study demonstrated an increased risk of multiple malignancies including lung and pancreatic cancers beyond the first year of diagnosis in patients with borderline ovarian tumors (BOTs), suggesting a potential shared etiology.

Clinical value of O-RADS combined with serum CA125 and HE4 for the diagnosis of ovarian tumours.

BACKGROUND: Ovarian tumors (OTs) are common gynecological tumors in women. It is very important to correctly distinguish benign and malignant OTs. PURPOSE: To assess the diagnostic performance of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) and evaluate the clinical value of O-RADS combined with serum carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) in differentiating benign from malignant OTs. MATERIAL AND METHODS: A retrospective analysis was performed on 431 cases including pathology and clinical data. The receiver operating characteristic (ROC) curve was drawn, and sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. RESULTS: In premenopausal women, O-RADS and O-RADS combined with serum CA125 and HE4 showed sensitivity at 92.2% and 94.8%, specificity at 91.8% and 93.4%, and accuracy at 91.9% and 93.8%, respectively. In postmenopausal women, the sensitivity of O-RADS, O-RADS combined with serum CA125 and HE4 was 94.8% and 95.8%, specificity was 83.9% and 93.6%, and accuracy was 90.5% and 95.6%, respectively. The sensitivity, specificity, and accuracy of O-RADS combined with CA125 and HE4 in premenopausal and postmenopausal women were higher than that of O-RADS (P<0.05). CONCLUSION: O-RADS has high diagnostic performance in OTs. When O-RADS is combined with CA125 and HE4 in the diagnosis of OTs, the sensitivity and specificity are improved, which is helpful to improve the diagnostic efficiency of OTs and has high clinical application value.

Mature Cystic Teratoma: An Integrated Review.

Ovarian dermoid cysts, also called mature cystic teratomas (MCTs), account for 69% of ovarian germ cell tumors in young women. The tumors are formed by tissues derived from three germ layers, and sebaceous materials are most commonly seen. The origin of MCTs is widely considered to be the germ cell origin, which completes meiosis I. The clinical symptoms vary widely, but 20% of tumors could be asymptomatic. The diagnosis of MCTs is usually made without difficulty by ultrasound and confirmed by histopathology post-operatively. The imaging findings have a high diagnostic value. The typical characteristics present in the sonographic images, including a dermoid plug or Rokitansky nodule, are considered strong evidence for a teratoma. Although the malignant transformation of MCTs is rare, it can occur in some cases, especially in women of advanced age. The treatment of MCTs depends on the risk of malignancy, the age of the patient, and the patient's fertility reserve requirement. In this article, we review the epidemiology, clinical symptoms, diagnosis criteria, cellular origin, and treatment of mature cystic teratomas.

[Sex cord tumors with annular tubules: About 4 cases and literature review]. / Les tumeurs des cordons sexuels à tubules annelés : à propos de 4 cas et revue de la littérature.

Sex cord tumor with annular tubules (SCTAT) is a rare ovarian tumor. It belongs to sex cord and stromal tumor of the ovary and represents less than 1% of cases. It includes two forms: the first one associated with Peuz-Jeghers syndrome and the second sporadic. We report 4 cases of SCTAT collected at the department of pathology of Salah Azaiez Institute of Tunis over the 12 last years. The age ranged from 10 to 32 years. Symptoms were non specific except for one case revealed by precocious puberty. One patient had Peutz-Jeghers syndrome associated. Tumors were unilateral. Gross findings showed often a solid tumor with yellow cut surface. Their size ranged from 0.5cm to 28cm. Their morphological features were characteristic. Immunohistochemistry showed that tumor cells expressed inhibin and claretinin. The treatment was surgical, often conservative. The diagnosis of malignancy wasn't focused on histological features, but on tumor extension, clinical course, and presence of metastases. Evolution was often favorable. We also performed a systematic review of the literature that identified 166 cases. Features of these cases were studied. We also compared these features between sporadic and syndromic forms and between benign and malignant forms. In conclusion, SCTAT is a rare tumor, usually benign. Its diagnosis is based on histological examination. There is a malignant potential especially in sporadic forms, estimated at 20%. Treatment is most often conservative, based on oophorectomy.

Pan-Cancer Detection and Typing by Mining Patterns in Large Genome-Wide Cell-Free DNA Sequencing Datasets.

BACKGROUND: Cell-free DNA (cfDNA) analysis holds great promise for non-invasive cancer screening, diagnosis, and monitoring. We hypothesized that mining the patterns of cfDNA shallow whole-genome sequencing datasets from patients with cancer could improve cancer detection. METHODS: By applying unsupervised clustering and supervised machine learning on large cfDNA shallow whole-genome sequencing datasets from healthy individuals (n = 367) and patients with different hematological (n = 238) and solid malignancies (n = 320), we identified cfDNA signatures that enabled cancer detection and typing. RESULTS: Unsupervised clustering revealed cancer type-specific sub-grouping. Classification using a supervised machine learning model yielded accuracies of 96% and 65% in discriminating hematological and solid malignancies from healthy controls, respectively. The accuracy of disease type prediction was 85% and 70% for the hematological and solid cancers, respectively. The potential utility of managing a specific cancer was demonstrated by classifying benign from invasive and borderline adnexal masses with an area under the curve of 0.87 and 0.74, respectively. CONCLUSIONS: This approach provides a generic analytical strategy for non-invasive pan-cancer detection and cancer type prediction.

Oncological and reproductive outcomes after fertility-sparing surgery in patients with seromucinous borderline ovarian tumor: Results of a large retrospective study.

OBJECTIVE: To evaluate the oncological and reproductive outcomes in patients with seromucinous borderline ovarian tumors (SMBOT) treated with fertility-sparing surgery (FSS). METHODS: We retrospectively reviewed the medical records of patients with SMBOT who underwent surgery between 2000 and 2019. A centralized histological review was performed and recurrence rates were compared between different surgical procedures. RESULTS: A total of 105 patients fulfilled the inclusion criteria, of whom 65 underwent FSS and 40 were treated with radical surgery (RS). Fourteen patients had recurrent disease after a median follow-up time of 59.6 months (range: 22.1-256.8 months). All but one relapsed with SMBOT. There was no significant difference in disease-free survival (DFS) between the two groups (P = 0.141). Multivariate analysis showed that only bilateral involvement was associated with increased recurrence (P = 0.008). In the subgroup of patients treated with conservative surgery, there was no significant difference in DFS with regard to surgical procedures (ovarian cystectomy vs salpingo-oophorectomy, P = 0.487). Of the 12 patients in the FSS group who developed recurrence, 11 underwent a second round of FSS and all remained alive with no evidence of disease at the end of follow-up. Of 20 patients desiring pregnancy, 16 patients were successful and resulted in 17 term deliveries. CONCLUSIONS: FSS is feasible for young patients who wish to preserve their fertility. Patients initially treated with ovarian cystectomy may be managed by close surveillance if post-operative imaging are negative. Repeat FSS remains a valuable alternative for young patients with recurrent SMBOT after thorough communication.

Lessons from a large nationwide cohort of 350 children with ovarian mature teratoma: A study in favor of ovarian-sparing surgery.

BACKGROUND: Ovarian mature teratoma (OMT) is a common ovarian tumor found in the pediatric population. In 10%-20% of cases, OMT occurs as multiple synchronous or metachronous lesions on ipsi- or contralateral ovaries. Ovarian-sparing surgery (OSS) is recommended to preserve fertility, but total oophorectomy (TO) is still performed. DESIGN: This study reviews the clinical data of patients with OMT, and analyzes risk factors for second events. A national retrospective review of girls under 18 years of age with OMTs was performed. Data on clinical features, imaging, laboratory studies, surgical reports, second events and their management were retrieved. RESULTS: Overall, 350 children were included. Eighteen patients (5%) presented with a synchronous bilateral form at diagnosis. Surgery was performed by laparotomy (85%) and laparoscopy (15%). OSS and TO were performed in 59% and 41% of cases, respectively. Perioperative tumor rupture occurred in 23 cases, independently of the surgical approach. Twenty-nine second events occurred (8.3%) in a median time of 30.5 months from diagnosis (ipsilateral: eight cases including one malignant tumor; contralateral: 18 cases; both ovaries: three cases). A large palpable mass, bilateral forms, at diagnosis and perioperative rupture had a statistical impact on the risk of second event, whereas the type of surgery or approach did not. CONCLUSION: This study is a plea in favor of OSS as the first-choice treatment of OMT when possible. Close follow-up during the first 5 years is mandatory considering the risk of 8.3% of second events, especially in cases with risk factors.