Predicting outcomes in malignant ovarian germ cell tumors using the modified International Germ Cell Cancer Collaborative Group classification system.

OBJECTIVES: The aim of our study was to evaluate the feasibility of the modified International Germ Cell Cancer Collaborative Group risk classification system in Chinese female patients with malignant ovarian germ cell tumors and to identify predictive factors to enhance the risk classification system. METHODS: In this retrospective cohort analysis, patients with malignant ovarian germ cell tumors who received surgery with/without chemotherapy were included. These patients had been followed-up by Peking Union Medical College Hospital between 2011 to 2020. Patients without complete medical records or no follow-up information were excluded. RESULTS: The study enrolled a total of 271 patients. The risk model classified 106 (39.1%) patients as good-, 84 (31%) as intermediate-, and 81 (29.9%) as poor-risk. With a median follow-up time of 34 months (range 2-147), 48 (17.7%) recurrence and 16 (5.9%) deaths were observed. The risk classification significantly correlated with 3 year disease-free survival and overall survival (log rank p<0.001 and p=0.003, respectively). The survival outcomes of disease-free survival and overall survival were not statistically different among risk groups in patients who received neoadjuvant chemotherapy (log rank p=0.77 and 0.41, respectively). Univariate and multivariable analysis showed that tumor stage (p=0.033, hazard ratio (HR) 2.05, 95% confidence interval (CI) 1.06 to 3.96) was significantly associated with relapse or progression of disease. Patients over age 40 years exhibited a poor prognosis. CONCLUSION: The modified International Germ Cell Cancer Collaborative Group risk classification system was efficacious in patients with malignant ovarian germ cell tumors and was significantly associated with disease-free survival and overall survival. Risk assessment after neoadjuvant chemotherapy may be more predictive than stratification at initial diagnosis. Age and tumor stage were definitive prognostic factors for germ cell tumors, which may need to be incorporated in the stratification system.

Secondary cytoreduction surgery for recurrent epithelial ovarian cancer patients after PARPi maintenance: A multicenter, randomized, controlled clinical trial.

BACKGROUND: Poly ADP-ribose polymerase inhibitors (PARPi) treatment has radically changed the treatment strategy for epithelial ovarian cancer. Cancer progression with PARPi maintenance is a new problem that has arisen in clinical practice, and the value of secondary cytoreduction surgery remains unknown. PRIMARY OBJECTIVE: To evaluate the benefits of secondary cytoreductive surgery and to clarify the sensitivity to platinum in patients with firstline or secondline recurrent epithelial ovarian cancer who have completed ≥6 months of PARPi maintenance. STUDY HYPOTHESIS: Carefully selected patients who progress on PARPi maintenance will benefit from secondary cytoreductive surgery. TRIAL DESIGN: This is a multicenter phase III trial. Eligible patients will be randomly assigned at a ratio of 1:1 to either the experimental or standard arm. Patients in the experimental arm will receive secondary cytoreductive surgery followed by platinum based chemotherapy, while patients in the standard arm will be provided with chemotherapy alone. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients diagnosed with firstline or secondline recurrent epithelial ovarian cancer who had previously received ≥4 cycles of platinum based chemotherapy in initial treatment followed by PARPi maintenance therapy for ≥6 months prior to recurrence. PRIMARY ENDPOINT: Progression free survival. SAMPLE SIZE: 400 patients. ESTIMATED DATES FOR COMPETING ACCRUAL AND PRESENTING RESULTS: Accrual completion is expected in December 2024 with results mature after 2 years of follow-up in 2026. TRIAL REGISTRATION: ClinicalTrials.gov NCT05607329.

Endometriosis-associated ovarian cancer: a different clinical entity.

OBJECTIVE: To compare survival outcomes and patterns of recurrence between endometriosis-associated ovarian cancer patients and non-endometriosis-associated ovarian cancer patients. METHODS: This retrospective study included data of consecutive patients with endometrioid or clear cell ovarian cancer treated at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano between January 2010 and June 2021. Patients were assigned to one of two groups according to the absence or presence of endometriosis together with ovarian cancer at final histological examination. Survival outcomes were assessed using Kaplan-Meier and Cox hazard models. Proportions in recurrence rate and pattern of recurrence were evaluated using the Fisher exact test. RESULTS: Overall, 83 women were included in the endometriosis-associated ovarian cancer group and 144 in the non-endometriosis-associated ovarian cancer group, respectively. Patients included in the non- endometriosis-associated ovarian cancer group had a shorter disease-free survival than those in the endometriosis-associated ovarian cancer group (23.4 (range 2.0-168.9) vs 60.9 (range 4.0-287.8) months; p<0.001). Univariable and multivariable analyses showed that the association with endometriosis, previous hormonal treatment, early stage at presentation, and endometrioid histology were related to better disease-free survival in the entire study population. Similarly, patients in the non-endometriosis-associated ovarian cancer group had a shorter median (range) overall survival than those in the endometriosis-associated ovarian cancer group (54.4 (range 0.7-190.6) vs 77.6 (range 4.5-317.8) months; p<0.001). Univariable and multivariable analyses showed that younger age at diagnosis, association with endometriosis, and early stage at presentation were related to better overall survival. The recurrence rate was higher in the non-endometriosis-associated ovarian cancer group (63/144 women, 43.8%) than in the endometriosis-associated ovarian cancer group (17/83 women, 20.5%; p<0.001). CONCLUSIONS: Endometriosis-associated ovarian cancer patients had significantly longer disease-free survival and overall survival than non-endometriosis-associated ovarian cancer patients, while the recurrence rate was higher in non-endometriosis-associated ovarian cancer patients.

Role of fertility-sparing surgery and further prognostic factors in borderline tumors of the ovary.

OBJECTIVE: Borderline tumors of the ovary are a rare group of ovarian neoplasms with distinctive histological features. Considering their favorable prognosis and occurrence at a younger age, fertility-sparing surgery may be considered. Several risk factors have been identified as contributing to a higher recurrence rate, while the impact of pathohistological features varies in the literature. This study aimed to analyze risk factors for recurrence in patients with borderline tumors of the ovary. METHODS: Analysis included patients treated with first diagnosis of a borderline tumor at our center between January 1997 and December 2022 to analyze disease-free survival and to identify the role of fertility-sparing surgery, defined as preservation of at least one ovary, pathohistological features, and other prognostic factors for relapse. All stages classified according to the International Federation of Gynecology and Obstetrics (FIGO) were included. RESULTS: Among 507 patients, 26 patients (5.2%) had a recurrence, with 21 (4.1%) showing borderline histology and 5 (1%) with invasive relapses. Recurrence rate was higher following fertility-sparing surgery (p<0.0001). Median follow-up period was 49.2 (range 42.0-57.6) months. Among 153 patients (30.2%) who had fertility-sparing surgery, 21 (13.7%) experienced a recurrence (including one invasive relapse). Fertility-sparing surgery (HR 20; 95% CI 6.9 to 60; p<0.001), FIGO stage I with bilateral presence of tumor (HR 6.4; 95% CI 1.3 to 31; p=0.020), FIGO stage II (HR 15; 95% CI 3.4 to 68; p<0.001), FIGO stages III-IV (HR 38; 95% CI 10 to 140; p<0.001) in comparison with FIGO stage I with unilateral tumor, microinvasion (HR 8.6; 95% CI 2.7 to 28; p<0.001), and micropapillary growth patterns (HR 4.4; 95% CI 1.8 to 10; p=0.001) were identified as independent risk factors for recurrence in multivariate analysis. None of these factors were associated with an increased risk of disease-related death. CONCLUSIONS: Our study showed that although a fertility-preserving approach is associated with increased recurrence rates of a borderline tumor, it does not affect overall survival and can therefore be regarded as oncologically safe for patients desiring to preserve fertility. Additionally, presence of micropapillary patterns and microinvasion were identified as prognostic risk factors.

Polycystic ovarian syndrome awareness among females in the UAE: a cross-sectional study.

BACKGROUND: Polycystic Ovarian Syndrome (PCOS) is a common hormonal disorder affecting females of reproductive age. Clinical guidelines recommend following the diagnostic criteria of PCOS based on an appropriate assessment of the patient's clinical presentation. Sufficient awareness among the population will prompt females to seek medical attention when necessary. This study aimed to assess knowledge and awareness about PCOS among females above the age of 18 years in the United Arab Emirates (UAE) and to correlate the level of awareness with women's backgrounds, demographics, and education levels. METHODS: This was a cross-sectional study conducted in early 2020. 430 females over the age of 18 years were conveniently selected and interviewed in the UAE using a 21-item questionnaire that assessed participants' awareness of PCOS as a term, its causes, symptoms, complications, treatment, and prevention. 414 entries were eligible for data analysis. IBM® SPSS® Statistics version 25 was used for data entry and analysis. RESULTS: 349 participants (84.3%) were familiar with the term PCOS. However, only 21.7% of them had sufficient awareness of the syndrome (95% CI = 17.77-25.71%). Being knowledgeable of PCOS was significantly associated with having a previous diagnosis (p = 0.002) and with studying or working in a medical field (p < 0.001). In addition, females who knew someone diagnosed with PCOS were 5 times more likely to be more aware compared to those who didn't (95% CI = 2.5-10.8; p < 0.001). Age, education level, and nationality showed no correlation with the level of awareness. CONCLUSIONS: Overall, the level of PCOS awareness was insufficient in the study sample. Participants whose source of information was medical practitioners demonstrated more accurate knowledge. Accordingly, awareness of PCOS needs to be raised among females in the UAE, aiding early diagnosis and improving patient-oriented outcomes.

Tubal histopathological abnormalities in BRCA1/2 mutation carriers undergoing prophylactic salpingo-oophorectomy: a case-control study.

OBJECTIVE: To describe tubal histopathological abnormalities in women with germline BRCA1/2 mutations and in controls. METHODS: Consecutive women with BRCA1/2 mutations undergoing bilateral salpingo-oophorectomy between 2010 and 2020 in two centers (San Gerardo Hospital, Monza and San Matteo Hospital, Pavia) were considered in this analysis and compared with controls who had the same surgical procedure for benign conditions. Frequency of p53 signature, serous tubal intraepithelial carcinoma, and high-grade serous ovarian cancer were compared between the two groups. RESULTS: A total of 194 women with pathogenic BRCA1/2 mutations underwent prophylactic salpingo-oophorectomy. Of these, 138 women (71%) had a completely negative histological examination, while in 56 (29%) patients an ovarian or tubal alteration was reported. Among controls, 84% of patients had a p53wt signature, while 16% had a p53 signature. There was no difference in the frequency of a p53 signature between cases and controls; however, women with BRCA1/2 mutations were more likely to have pre-malignant or invasive alterations of tubal or ovarian epithelium (p=0.015). Among mutation carriers, older age both at genetic testing and at surgery was associated with an increased risk of having malignancies (OR=1.07, p=0.006 and OR=1.08, p=0.004, respectively). The risk of malignancy seems to be increased in patients with a familial history of high-grade serous ovarian cancer. Previous therapy with tamoxifen was significantly more frequent in patients with malignant lesions (40.0% vs 21.3%, p=0.006). CONCLUSION: We found that a p53 signature is a frequent finding both in BRCA1/2 mutation carriers and in controls, while pre-invasive and invasive lesions are more frequent in BRCA1/2 mutation carriers. Genetic and clinical characteristics are likely to affect the progression to malignancy.

Severe Paraneoplastic Dermatomyositis in a Patient With High-Grade Serous Ovarian Cancer.

BACKGROUND: Paraneoplastic dermatomyositis following a diagnosis of ovarian cancer is rare. There are very few cases reported on the management of severe forms. CASE: We report the case of a 50-year-old woman diagnosed with stage IIIC high-grade serous ovarian cancer and a severe form of paraneoplastic dermatomyositis requiring mechanical ventilation. She had significant comorbidities further adding to the complexity of the chemotherapy regimen. Intravenous immunoglobulin and corticosteroids were also administered. The dermatomyositis remained poorly controlled, and the patient was ultimately referred to palliative care. CONCLUSION: The necessity to treat the underlying neoplasia creates a fine balance between the aggressive treatments required and the clinical state of the patient. Multidisciplinary collaboration is warranted to offer best management.

A Stepwise Strategy to Minimally Invasive Salpingo-Oophorectomy in the Post-Hysterectomy Patient.

Post-hysterectomy salpingo-oophorectomy can be surgically complex. Up to 9% of women who chose ovarian preservation at the time of hysterectomy require future adnexal surgery. Some of the common indications for post-hysterectomy salpingo-oophorectomy are persistent adnexal masses or masses with concern for malignancy, chronic pelvic pain, and risk-reducing surgery. This video presents a 5-step strategy to facilitate a post-hysterectomy bilateral salpingo-oophorectomy to include pelvic and abdominal exploration, restoring normal anatomy, identification of the ureter, isolation, coagulation and transection of the infundibulopelvic ligament, and, lastly, hemostasis with re-evaluation of ureter. This stepwise procedure was highlighted in a patient with a prior total abdominal hysterectomy and a complex adnexal mass. We utilize these techniques on the side without anatomic abnormality and then safely apply this same 5-step strategy to remove a more challenging adnexal mass on the opposite side. We describe a 5-step surgical strategy to ensure safe, efficient, and reproducible salpingo-oophorectomy in the post-hysterectomy patient using a minimally invasive approach. Although this surgery can be challenging to perform in post-hysterectomy patients given anatomical variance and adhesive disease, by following these 5 simple principles we aim to standardize and simplify this potentially difficult procedure.

Interval debulking surgery is not worth the wait: a National Cancer Database study comparing primary cytoreductive surgery versus neoadjuvant chemotherapy.

OBJECTIVE: In previous studies, neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary cytoreductive surgery as initial treatment for advanced epithelial ovarian cancer. Our study aimed to compare surgical and survival outcomes between the two treatments in a large national database. METHODS: Data were extracted from the National Cancer Database from January 2004 to December 2015. Patients with FIGO (International Federation of Gynecologists and Obstetricians) stage III-IV epithelial ovarian cancer and known sequence of treatment were included: primary cytoreductive (surgery=26 717 and neoadjuvant chemotherapy=9885). Tubal and primary peritoneal cancer diagnostic codes were not included. Residual disease after treatment was defined based on recorded data: R0 defined as microscopic or no residual disease; R1 defined as macroscopic residual disease. Multivariate Cox proportional HR was used for survival analysis. Multivariate logistic regression analysis was utilized to compare mortality between groups. Outcomes were adjusted for significant covariates. Validation was performed using propensity score matching of significant covariates. RESULTS: A total of 36 602 patients were included in the analysis. Patients who underwent primary cytoreductive surgery had better survival than those treated with neoadjuvant chemotherapy followed by interval surgery, after adjusting for age, co-morbidities, stage, and residual disease (p<0.001). Primary cytoreductive surgery patients with R0 disease had best median survival (62.6 months, 95% CI 60.5-64.5). Neoadjuvant chemotherapy patients with R1 disease had worst median survival (29.5 months, 95% CI 28.4-31.9). There were small survival differences between primary cytoreductive surgery with R1 (38.9 months) and neoadjuvant chemotherapy with R0 (41.8 months) (HR 0.93, 95% CI 0.87 to 1.0), after adjusting for age, co-morbidities, grade, histology, and stage. Neoadjuvant chemotherapy had 3.5 times higher 30-day mortality after surgery than primary cytoreductive surgery (95% CI 2.46 to 5.64). The 90-day mortality was higher for neoadjuvant chemotherapy in multivariate analysis (HR 1.31, 95% CI 1.06 to 1.61) but similar to primary cytoreductive surgery after excluding high-risk patients. CONCLUSIONS: Most patients with advanced epithelial ovarian cancer may benefit from primary cytoreductive surgery. Patients treated with neoadjuvant chemotherapy should be those with co-morbidities unfit for surgery.

Guideline No. 404: Initial Investigation and Management of Benign Ovarian Masses.

OBJECTIVE: To provide recommendations for a systematic approach to the initial investigation and management of a benign ovarian mass and facilitate patient referral to a gynaecologic oncologist for management. INTENDED USERS: Obstetricians, gynaecologists, family physicians, internists, nurse practitioners, radiologists, general surgeons, medical students, medical residents, fellows, and other health care providers. TARGET POPULATION: Women ≥18 years of age presenting for evaluation of an ovarian mass (including simple and unilocular cystic masses, endometriomas, dermoids, fibromas, and hemorrhagic cysts) who are not acutely symptomatic and without known genetic predisposition to ovarian cancer. OUTCOMES: This guideline aims to encourage conservative management and help reduce unnecessary surgery and long-term health complications, maintain fertility, and decrease operative costs and improve overall patient care and outcomes by providing criteria for referral of patients with ultrasound imaging findings suggestive of a malignant mass to a gynaecologic oncologist. EVIDENCE: Databases searched: Medline, Cochrane, and PubMed. Medical terms used: benign asymptomatic and symptomatic ovarian cysts, adnexal masses, oophorectomy, ultrasound diagnosis of cysts, simple ultrasound rules, surgical and medical therapies for cysts, screening for ovarian cancer, ovarian torsion, and menopause. Initial search was completed by 2017 and updated in 2018. Exclusion criteria were malignant ovarian cystic masses, endometriosis therapies, and other adnexal pathologies unrelated to the ovary. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the authors. The Society of Obstetricians and Gynaecologists of Canada's Board of Directors approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation methodology framework. BENEFITS, HARMS, COSTS: Implementation of the recommendations could reduce costs due to unnecessary surgeries and hospitalizations and reduce lost work days and the risk of loss of fertility, early menopause, and surgical complications. SUMMARY STATEMENTS (GRADE RATINGS IN PARENTHESES): RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

Abnormal aggregation of myeloid-derived suppressor cells in a mouse model of cyclophosphamide-induced premature ovarian failure.

Oocytes are extremely sensitive to radiation and chemotherapy, and premature ovarian failure (POF) is one of the side effects of anti-tumor therapy. The pathogenesis of POF is very complex and still not fully elucidated. A mouse POF model was established after 14 days of cyclophosphamide injection. POF mice presented ovarian atrophy, destroyed follicular structure, a reduction in the number of primordial and mature follicles, and an decrease in the number of corpora luteal along with increased level of follicle-stimulating hormone (FSH), decreased levels of estradiol (E2), and anti-Mullerian hormone (AMH). Additionally, the proportion of bone marrow myeloid-derived suppressor cells (MDSCs) in peripheral blood, spleen, and ovarian tissue increased. MDSCs were mainly distributed around follicles and corpora luteal. Levels of mTOR and p-mTOR increased in ovarian tissue and inhibition of mTOR with rapamycin reduced the aggregation of MDSCs in peripheral blood, spleen, and ovarian tissue. This investigation sheds new light on the modulatory role of mTOR and demonstrates that an increase in MDSC number may play a key role in the pathological reaction during POF. Inhibition of mTOR and reduction of MDSCs in the ovary may represent a novel strategy for the treatment of POF.

Method Comparison Using 2 Point-of-Care Meters and a Reference Analyzer for Measuring Blood Triglycerides in Psittacine Birds.

Female reproductive disorders, such as chronic egg laying, are common in captive psittacine birds. While a disease diagnosis related to reproductive disorders can often be accomplished by physical examination and diagnostic imaging, monitoring of the response to environmental modification and medical treatment is more challenging. Monitoring ideally would involve measurement of luteinizing hormone or estrogen to assess ovarian activity. However, the amount of blood required for hormone analysis is greater than the small sample size that one can collect from these birds. Additionally, the lack of reference intervals limits their use as a diagnostic tool. Because plasma triglyceride increases during sustained estrogen release from the ovary, it may be used as an alternative method for assessing ovarian activity in birds. Point-of-care (POC) analyzers for measuring lipids in human plasma use very small sample volumes and have been used for measuring triglycerides in animals, including chickens. The authors therefore performed a method comparison study with 2 POC analyzers and a reference analyzer and plasma and whole blood from psittacine birds to determine whether these meters are suitable for triglyceride measurement in a known population of psittacine birds. Correlation, Deming regression, and Bland-Altman analyses were used to assess performance, and the total observed error for each meter relative to the reference analyzer was calculated. One of the meters exhibited fair performance and, with species-specific reference intervals, is likely to be clinically useful for triglyceride measurement in psittacine birds. The other meter demonstrated poor performance with unacceptable error, and its use for this purpose is strongly discouraged.

Role of oxylipins in ovarian function and disease: A comprehensive review.

Ovaries are essential for healthy female reproduction, with the follicles as their fundamental functional units, which consist of an oocyte and surrounding granulosa cells. The development and formation of follicles in the ovaries are closely linked to reproductive health. Oxylipins refer to oxidative metabolites produced from the oxidation of polyunsaturated fatty acids, either through automatic oxidation or with the help of specific enzymes. They play crucial regulatory roles in the immune system, oxidative stress, and inflammatory reactions and are intimately linked to the development of numerous illnesses, such as diabetes, heart disease, asthma, and Alzheimer's disease. Furthermore, oxylipins have a complex relationship with ovarian function, and both prostaglandins and leukotrienes produced by arachidonic acid affect processes such as follicle growth and development, ovulation, and hormone regulation. The synthesis and metabolism of oxylipins in the ovaries are finely regulated. Oxylipin dysregulation has been linked to various ovarian diseases, including endometriosis, polycystic ovary syndrome, ovarian cancer, and premature ovarian insufficiency. In addition, potential therapeutic targets and interventions targeting the oxylipin pathway for the treatment of ovarian diseases have become a prominent research focus, including regulating the enzymes responsible for oxylipin synthesis, using anti-inflammatory agents, and regulating lipid metabolism. Recent research has been directed towards improving the reproductive outcomes of women with ovarian diseases through this series of interventions. An overview of the role of oxylipins in ovarian function and disease is provided in this article, which will aid researchers in understanding the current state of the field and in identifying future directions.