Genomic alterations in ovarian endometriosis and subsequently diagnosed ovarian carcinoma.

STUDY QUESTION: Can the alleged association between ovarian endometriosis and ovarian carcinoma be substantiated by genetic analysis of endometriosis diagnosed prior to the onset of the carcinoma? SUMMARY ANSWER: The data suggest that ovarian carcinoma does not originate from ovarian endometriosis with a cancer-like genetic profile; however, a common precursor is probable. WHAT IS KNOWN ALREADY: Endometriosis has been implicated as a precursor of ovarian carcinoma based on epidemiologic studies and the discovery of common driver mutations in synchronous disease at the time of surgery. Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are the most common endometriosis-associated ovarian carcinomas (EAOCs). STUDY DESIGN, SIZE, DURATION: The pathology biobanks of two university hospitals in Sweden were scrutinized to identify women with surgically removed endometrioma who subsequently developed ovarian carcinoma (1998-2016). Only 45 archival cases with EAOC and previous endometriosis were identified and after a careful pathology review, 25 cases were excluded due to reclassification into non-EAOC (n = 9) or because ovarian endometriosis could not be confirmed (n = 16). Further cases were excluded due to insufficient endometriosis tissue or poor DNA quality in either the endometriosis, carcinoma, or normal tissue (n = 9). Finally 11 cases had satisfactory DNA from all three locations and were eligible for further analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Epithelial cells were collected from formalin-fixed and paraffin-embedded (FFPE) sections by laser capture microdissection (endometrioma n = 11) or macrodissection (carcinoma n = 11) and DNA was extracted. Normal tissue from FFPE sections (n = 5) or blood samples collected at cancer diagnosis (n = 6) were used as the germline controls for each included patient. Whole-exome sequencing was performed (n = 33 samples). Somatic variants (single-nucleotide variants, indels, and copy number alterations) were characterized, and mutational signatures and kataegis were assessed. Microsatellite instability and mismatch repair status were confirmed with PCR and immunohistochemistry, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: The median age for endometriosis surgery was 42 years, and 54 years for the subsequent ovarian carcinoma diagnosis. The median time between the endometriosis and ovarian carcinoma was 10 (7-30) years. The data showed that all paired samples harbored one or more shared somatic mutations. Non-silent mutations in cancer-associated genes were frequent in endometriosis; however, the same mutations were never observed in subsequent carcinomas. The degree of clonal dominance, demonstrated by variant allele frequency, showed a positive correlation with the time to cancer diagnosis (Spearman's rho 0.853, P < 0.001). Mutations in genes associated with immune escape were the most conserved between paired samples, and regions harboring these genes were frequently affected by copy number alterations in both sample types. Mutational burdens and mutation signatures suggested faulty DNA repair mechanisms in all cases. LARGE SCALE DATA: Datasets are available in the supplementary tables. LIMITATIONS, REASONS FOR CAUTION: Even though we located several thousands of surgically removed endometriomas between 1998 and 2016, only 45 paired samples were identified and even fewer, 11 cases, were eligible for sequencing. The observed high level of intra- and inter-heterogeneity in both groups (endometrioma and carcinoma) argues for further studies of the alleged genetic association. WIDER IMPLICATIONS OF THE FINDINGS: The observation of shared somatic mutations in all paired samples supports a common cellular origin for ovarian endometriosis and ovarian carcinoma. However, contradicting previous conclusions, our data suggest that cancer-associated mutations in endometriosis years prior to the carcinoma were not directly associated with the malignant transformation. Rather, a resilient ovarian endometriosis may delay tumorigenesis. Furthermore, the data indicate that genetic alterations affecting the immune response are early and significant events. STUDY FUNDING/COMPETING INTEREST(S): The present work has been funded by the Sjöberg Foundation (2021-01145 to K.S.; 2022-01-11:4 to A.S.), Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965552 to K.S.; 40615 to I.H.; 965065 to A.S.), Swedish Cancer Society (21-1848 to K.S.; 21-1684 to I.H.; 22-2080 to A.S.), BioCARE-A Strategic Research Area at Lund University (I.H. and S.W.-F.), Mrs Berta Kamprad's Cancer Foundation (FBKS-2019-28, I.H.), Cancer and Allergy Foundation (10381, I.H.), Region Västra Götaland (A.S.), Sweden's Innovation Agency (2020-04141, A.S.), Swedish Research Council (2021-01008, A.S.), Roche in collaboration with the Swedish Society of Gynecological Oncology (S.W.-F.), Assar Gabrielsson Foundation (FB19-86, C.M.), and the Lena Wäpplings Foundation (C.M.). A.S. declares stock ownership and is also a board member in Tulebovaasta, SiMSen Diagnostics, and Iscaff Pharma. A.S. has also received travel support from EMBL, Precision Medicine Forum, SLAS, and bioMCC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

A comprehensive review of the new FIGO classification of ovulatory disorders.

BACKGROUND: The World Health Organization (WHO) system for the classification of disorders of ovulation was produced 50 years ago and, by international consensus, has been updated by the International Federation of Gynecology and Obstetrics (FIGO). OBJECTIVE AND RATIONALE: This review outlines in detail each component of the FIGO HyPO-P (hypothalamic, pituitary, ovarian, PCOS) classification with a concise description of each cause, and thereby provides a systematic method for diagnosis and management. SEARCH METHODS: We searched the published articles in the PubMed database in the English-language literature until October 2022, containing the keywords ovulatory disorders; ovulatory dysfunction; anovulation, and each subheading in the FIGO HyPO-P classification. We did not include abstracts or conference proceedings because the data are usually difficult to assess. OUTCOMES: We present the most comprehensive review of all disorders of ovulation, published systematically according to the logical FIGO classification. WIDER IMPLICATIONS: Improving the diagnosis of an individual's ovulatory dysfunction will significantly impact clinical practice by enabling healthcare practitioners to make a precise diagnosis and plan appropriate management.

Ovarian Torsion and Oophorectomy in Childhood: A Case Report.

BACKGROUND: Ovarian torsion in infants can be asymptomatic or may present with abdominal mass and malnutrition. It is an uncommon and non-specific condition in children. We report a girl who underwent detorsion and ovariopexy for suspected ovarian torsion after a previous oophorectomy. The role of progesterone therapy is determined in reducing the size of adnexal mass. CASE PRESENTATION: The patient was diagnosed with right ovarian torsion and underwent an oophorectomy at one year of age. About 18 months later, she was diagnosed with left ovarian torsion and underwent detorsion with lateral pelvic fixation. Despite the pelvic fixation of the ovary, a continuous increase in the volume of the ovarian tissue was evident during successive ultrasounds. Progesterone therapy was started at five years of age in order to prevent retorsion and preserve the ovarian tissue. In successive follow-ups during the therapy, ovarian volume decreased, and its size (27*18 mm) was restored. CONCLUSION: The presented case reminds doctors of the possibility of ovarian torsion in young girls with pelvic pain. More research is needed on the use of hormonal drugs, such as progesterone, in similar cases.

Fertility preserving management of ovarian torsion.

OBJECTIVE: To analyze characteristics of acute and chronic ovarian torsion, review treatment recommendations, and present possible surgical techniques for fertility preservation in young women. DESIGN: Literature review and demonstration of perioperative management of ovarian torsion using radiologic images and intraoperative video footage. Ovarian torsion is mostly mentioned in context of gynecologic emergencies, where acute ovarian torsion with arterial obstruction leads to ovarian ischemia and necrosis. However, ovarian torsion can also occur as a partial or intermittent torsion with venous and lymphatic obstruction, followed by ovarian swelling. In both cases, surgical management of ovarian torsion commonly includes oophorectomy, although leading guidelines recommend preservation of the ovary. We here aimed to raise awareness for the clinical features of ovarian torsion and demonstrate adequate perioperative management, thereby avoiding surgical overtreatment in young women. SETTING: Medical University of Vienna, Department of Obstetrics and Gynecology. PATIENT(S): We present a case of acute ovarian torsion with a consequently ischemic ovary as well as a case of chronic ovarian torsion with related massive ovarian edema. The patients included in this video gave consent for publication of the video and posting of the video online, including social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus, etc.), and other applicable sites. INTERVENTION(S): Laparoscopic management with detorsion of the torquated ovaries, cystectomy on an ischemic ovary and oophoropexy to the pelvic side wall and utero-ovarian ligament to prevent recurrence. MAIN OUTCOME MEASURES: Postoperative relief of pain and normalization of ovarian size and morphology on ultrasound imaging. RESULTS: The current cases show successful conservative surgical management of ovarian torsion, hence preserving hormonal function and fertility in young women. CONCLUSION: Although it is recommended to preserve fertility in young women affected by ovarian torsion, surgical overtreatment by means of oophorectomy is still common in clinical routine. Increasing awareness for the clinical characteristics of acute and chronic ovarian torsion, as well as for the importance of preservation of the ovary, is crucial. We therefore believe that ovarian torsion and its surgical management deserve increased attention in the future.

Ovarian torsion in the pediatric population: predictive factors for ovarian-sparing surgery-an international retrospective multicenter study and a systematic review.

STUDY OBJECTIVE: Ovarian torsion (OT) in pediatric age is a challenging condition to diagnose and treat. To date, there is still no clear consensus about its management. Our aim was to assess some possible associated factors that can help surgeons in decision-making. DESIGN: We conducted a retrospective multicentric study of pediatric OT surgically treated between 2010 and 2020 in six Italian and German institutions, comparing our findings with a literature review of the last 10 years (2010-2020). PARTICIPANTS: Patients aged 0-18 years with a diagnosis of OT intraoperatively confirmed and surgically treated at the involved institutions. RESULTS: Ninety-seven patients with a mean age at diagnosis of 8.37 years were enrolled in the study. Severe abdominal pain was present in 82 patients (84.5%). Eighty children (82.5%) presented an enlarged ovary with an US diameter > 5 cm and only 32 (40%) of them underwent conservative surgery. A laparoscopic approach was performed in 60 cases (61.9%) although in 15 (15.5%) conversion to open surgery was deemed necessary. A functional cyst was present in 49 patients (50.5%) while 11 children (11.3%) suffered from OT on a normal ovary. CONCLUSIONS: Our results showed that a post-menarchal age (p = .001), a pre-operative US ovarian size < 5 cm, (p = .001), the presence of severe abdominal pain (p = .002), a laparoscopic approach (p < .001), and the presence of a functional cyst (p = .002) were significantly associated with conservative surgery.

Primary ovarian abscess in virginal young woman with huge endometriosis cyst: A case report.

RATIONALE: Primary ovarian abscess which develops as an isolated lesion without simultaneous tubal infection is a rare entity. Ovarian abscess (OA) is a serious complication of pelvic inflammatory disease (PID) rarely seen in virginal girls. Early diagnosis and treatment are essential to prevent further sequela including infertility, ectopic pregnancy, and chronic pelvic pain. PATIENT CONCERNS: A 19-year-old virginal girl who presented with abdominal pain and pelvic mass with no risk factors. DIAGNOSES: Laparoscopic surgery was performed to confirm a primary ovarian abscess in the adolescent virginal female with a huge endometriosis cyst. INTERVENTION: Ovarian abscess with extensive intestinal adhesions was determined during the laparoscopic operation. Abscess drainage and postoperative antibiotic therapy cured the patient. OUTCOME: After the surgery, the CRP level on the day of discharge was 3.18 mg/d. The histological findings revealed a cystic tissue sample with the fibrous wall infiltrated by neutrophilic granulocytes, and ectopic endometrium, suggesting abscess formation in the ovary and endometriosis cyst. LESSONS: Although primary ovarian abscess in an adolescent virginal female is rare, given the severity of outcomes following ovarian abscess, this pathology should be considered in the differential diagnosis of virginal adolescents with fever and abdominal pain.

High risk and low prevalence diseases: Ovarian torsion.

INTRODUCTION: Ovarian torsion is a rare, frequently misdiagnosed condition that carries with it a high rate of morbidity. OBJECTIVE: This review highlights the pearls and pitfalls of ovarian torsion, including presentation, evaluation, and management in the emergency department (ED) based on current evidence. DISCUSSION: Ovarian torsion is one of the most common gynecological surgical emergencies and occurs with complete or partial rotation of the ovary along the supporting ligaments, obstructing vascular flow. Several risk factors include the presence of an ovarian mass or cyst. The most common population affected includes reproductive aged women, though cases also occur in premenarchal females, pregnant women, and postmenopausal women. Abdominal or pelvic pain is common but is not always sudden in onset or severe. Nausea and vomiting occur in 70%. Ultrasound can assist with diagnosis, but a normal ultrasound examination cannot exclude the diagnosis. Computed tomography with intravenous contrast can assist with diagnosis. Treatment includes emergent gynecologic consultation for surgical detorsion, along with symptomatic therapy in the ED. CONCLUSIONS: An understanding of ovarian torsion can assist emergency clinicians in diagnosing and managing this disease.

Ovarian torsion: diagnosis, surgery, and fertility preservation in the pediatric population.

Ovarian torsion is rare in the pediatric population. Delayed diagnosis can significantly impact fertility. The aim of this review is to highlight current knowledge regarding clinical presentation, diagnosis, surgical management, and follow-up in the pediatric population. Whilst the presentation is often very unspecific, most children will present with sudden severe unilateral pelvic pain associated with vomiting. A key diagnostic test is pelvic ultrasonography, which may help demonstrate an asymmetric enlarged ovary with peripherally displaced follicles. In the pediatric population, ovarian torsion may occur in a normal ovary. However, underlying lesions can be found in half of cases. Benign neoplasms (teratomas or cystic lesions) represent the commonest etiology, with the risk of malignancy being less than 2%. Surgical management should be focused on fertility preservation. This is achievable through ovarian detorsion ± ovarian cystectomy ± oophoropexy to avoid recurrence. Follow-up studies demonstrate excellent recovery rates of detorsed ovaries including those with ischemic appearances. What is Known: • Ovarian torsion is a rare diagnosis in the pediatric population. • Aspecific symptoms and differential diagnoses lead to missed or delayed diagnosis increasing the risk of oophoprectomy and further infertility. What is New: • Reviewing the latest knowledge about clinical presentation, diagnostic, surgical management, and follow-up of ovarian torsion in the pediatric population. • Adiponectin was negatively associated with diastolic blood pressure and HOMA-IR, and chemerin was negatively associated with glucose.

Spontaneous reduction age for ovarian hernia in early infancy.

BACKGROUND: Many articles recommend early surgery for ovarian hernia to avoid the risk of ovarian torsion. However, while ovarian hernia is known to undergo spontaneous reduction (SR) in early infancy, few reports have described the timing of SR. We therefore investigated the clinical features of SR for ovarian hernia in early infancy. METHODS: A total of 610 girls were diagnosed with inguinal hernia between 2008 and 2018. We focused on infants who had an ovarian hernia onset in the first 3 months of age. We reviewed the age retrospectively at the onset of hernia and age at SR. The data were compared statistically using the Kaplan-Meier method. RESULTS: Sixty-one infants with inguinal hernia were included in this study. Thirty-nine patients (64%) had ovarian hernia. The mean age at the onset of hernia was 44 ± 17 days of age. Thirty cases underwent SR (77%). A Kaplan-Meier analysis showed that 75% of ovarian hernias underwent SR by 6 months of age. There were no cases of ovarian torsion. CONCLUSIONS: Most cases of ovarian hernia underwent SR, so patients with ovarian hernia in early infancy might be treated by elective surgery after 6 months of age.

Development of a fertility risk calculator to predict individualized chance of ovarian failure after chemotherapy.

PURPOSE: To develop an innovative machine learning (ML) model that predicts personalized risk of primary ovarian insufficiency (POI) after chemotherapy for reproductive-aged women. Currently, individualized prediction of a patient's risk of POI is challenging. METHODS: Authors of published studies examining POI after gonadotoxic therapy were contacted, and six authors shared their de-identified data (N = 435). A composite outcome for POI was determined for each patient and validated by 3 authors. The primary dataset was partitioned into training and test sets; random forest binary classifiers were trained, and mean prediction scores were computed. Institutional data collected from a cross-sectional survey of cancer survivors (N = 117) was used as another independent validation set. RESULTS: Our model predicted individualized risk of POI with an accuracy of 88% (area under the ROC 0.87, 95% CI: 0.77-0.96; p < 0.001). Mean prediction scores for patients who developed POI and who did not were 0.60 and 0.38 (t-test p < 0.001), respectively. Highly weighted variables included age, chemotherapy dose, prior treatment, smoking, and baseline diminished ovarian reserve. CONCLUSION: We developed an ML-based model to estimate personalized risk of POI after chemotherapy. Our web-based calculator will be a user-friendly decision aid for individualizing risk prediction in oncofertility consultations.

Copenhagen Index versus ROMA in preoperative ovarian malignancy risk stratification: Result from the first Vietnamese prospective cohort study.

OBJECTIVES: This study aimed to evaluate the diagnostic performances of the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA) in the preoperative prediction of ovarian cancer. METHODS: In a prospective cohort study, data were collected from 475 patients with ovarian masses diagnosed by gynecologic examination / ultrasound who were hospitalized at the Departments of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital and Hue Central Hospital, Vietnam, between January 2018 and June 2020. ROMA and CPH-I were calculated based on measurements of serum carbohydrate antigen (CA-125) and human epididymis protein (HE4). The final diagnosis was based on clinical features, radiologic and histologic findings, and the International Federation of Gynecology and Obstetrics (FIGO) 2014 stages of ovarian cancer were recorded. Matching the values of ROMA and CPH-I to postoperative histopathology reports resulted in the preoperative prediction values. RESULTS: Among the 475 women, 408 had benign tumors, 5 had borderline tumors and 62 had malignant tumors. The two indices showed similar discriminatory performances with no significant differences (p > 0.05). At an optimal cut-off, the sensitivities/specificities of ROMA and CPH-I for ovarian cancer diagnosis were 74.2% and 91.8%, 87.1% and 78.5%, respectively. The optimal cut-off for CPH-I was 1.89%. The areas under the ROC curves (AUCs) of ROMA and CPH-I were 0.882 (95% CI: 0.849-0.909) and 0.898 (95% CI: 0.867-0.924), respectively. CONCLUSIONS: The introduction of the Copenhagen Index to help stratify the malignancy risk of ovarian tumors, irrespective of menopausal status, might be applied as a simple alternative with a similar efficacy to ROMA in clinical practice.

Long-Term Medical Therapy after Laparoscopic Excision of Ovarian Endometriomas: Can We Reduce and Predict the Risk of Recurrence?

OBJECTIVES: Up to 32% of women experience anatomic recurrence after conservative surgery for endometriomas, while pain recurs in 10-40% of cases. Long-term postoperative hormonal therapy is recommended to prevent disease recurrence. We evaluated the efficacy of long-term therapy with estroprogestins (EPs) or progestins (Ps) in preventing endometrioma recurrence, as identifiable cysts and subjective symptoms, after laparoscopic excision. DESIGN: This retrospective cohort study included 375 women submitted to laparoscopic endometrioma excision. Women were followed up at 6 and 12 months and then yearly after surgery. Based on postoperative medical therapy, women were divided into 4 groups: nonusers, cyclic EP users, continuous EP users, and progestogen users. Materials, Setting, Methods: Anamnestic and anthropometric characteristics were collected as well as clinical and surgical data. Gynecological examination, and transvaginal and transabdominal ultrasound scans were performed. Pain (numerical rating score >5) and endometrioma recurrence at ultrasound (ovarian cyst with typical sonographic features ≥10 mm in mean diameter) were recorded at each examination. The reoperation rate in women with recurrence was investigated. RESULTS: The median follow-up was 3.7 years with a maximum of 16.7 years. Most patients used EPs (119 cyclic and 61 continuous users), 95 used P, and 100 were nonusers. In 135 women (36%), endometriotic cyst recurrence was diagnosed, with a mean diameter of 18.7 ± 10.8 mm (range 10-55 mm). The median recurrent cyst-free time was 7.9 years (95% CI 5.8-10.8). Dysmenorrhea was the first symptom to reappear, affecting 162 patients (43.2%). Upon multivariable regression analysis, continuous users had a lower risk of relapse (OR 0.56, 95% CI 0.32-0.99), in terms of both cysts and symptom recurrence, than patients who received no medications. The reoperation rate was 16.2%. LIMITATIONS: The main limitation of this study is its retrospective design. Also, women switching therapies throughout the follow-up period were sorted into one of the study groups based on the longest treatment taken, without considering the discontinuation rates. CONCLUSIONS: Long-term EPs, administered in a continuous regimen and starting immediately after conservative surgery for endometriomas, seem to reduce the disease recurrence risk.

Hyperthecosis: an underestimated nontumorous cause of hyperandrogenism.

Hyperthecosis is defined as the presence of nests of luteinized theca cells in the ovarian stroma. Persistent testosterone released by ovarian theca cells is unmasked postmenopausally through the loss of granulosa cell-mediated aromatization of testosterone to estradiol. Ovarian hyperthecosis (OH) usually presents with symptoms of hyperandrogenism and is often described as a severe or extreme form of Polycystic Ovary Syndrome (PCOS). Serum testosterone levels in excess of 150 ng/dl (>5.2 nmol/l) are seen in affected patients and this threshold is used to confirm a diagnosis. Treatment of hyperthecosis is multi-faceted. It addresses the attendant hyperandrogenism (hirsutism and virilization) as well as metabolic complications such as obesity and insulin resistance. Ultimately, laparoscopic bilateral salpingo-oophorectomy is definitive treatment. This remains the treatment of choice in postmenopausal women whereas treatment using GnRH agonists may be used in women of reproductive age, especially younger women. Nevertheless, if serum testosterone remains elevated despite several months of therapy with a GnRH agonist, surgery is often required for biopsy sample collection and further definitive therapy. In order to mitigate the common clinical manifestations of hyperandrogenism, anti-androgen therapy (either cyproterone acetate or spironolactone) may be used to suppress the actions of testosterone on tissues. In patients with impaired glucose metabolism and insulin resistance, Metformin should also be considered as part of treatment. Combined, such a treatment regimen will often lead to decreased ovarian androgen secretion.

Ovarian torsion: can we save the ovary?

OBJECTIVE: The purpose of this study is to evaluate the correlation between visually appearing ovarian necrosis and necrosis in histopathology in patients with ovarian torsion; and to identify predictive factors of ovarian necrosis. METHODS: This is a retrospective study. All women admitted to the hospital with a diagnosis of suspected ovarian torsion from January 2014 to December 2018 were recruited. Forty-two patients with a confirmed diagnosis of ovarian torsion were finally included. Correlation analysis was done between visual judgement of ovarian necrosis and necrosis in histopathology. Chi-square was performed to analyze dependence between time from pain onset to surgery, ovarian size in ultrasound, Doppler flow, and histopathological analysis. RESULTS: Thirty-one ovaries were visually judged as necrotic. Only five of them (16%) had histopathologically confirmed necrosis, 20 (64.5%) had hemorrhage or congestion, and 6 (19%) had normal ovarian tissue, p = 0.349. Development of ovarian necrosis showed to be dependent on time from onset of pain to surgery. All patients with necrotic ovaries in histopathology underwent surgery after 24 h of pain onset, while there was no necrosis in those who had surgery before 24 h. (p = < 0.05). There was no relationship between ovarian size measured by ultrasound and necrosis (p = 0.265), as well as color flow in ultrasound and necrosis (p = 0.388). CONCLUSION: Visual assessment of ovarian necrosis intraoperatively is not a good predictor of real necrosis in histopathology. To preserve the ovary, surgical management should not be delayed.

Low serum T3 levels are associated with false-positive results when using the risk of ovarian malignancy algorithm (ROMA) in women with benign ovarian disease.

OBJECTIVE: We investigated factors that could cause false-positive results when using the risk of ovarian malignancy algorithm (ROMA) for assessing ovarian cancer risk. MATERIALS AND METHODS: ROMA scores were calculated from patients followed surgery to remove a pelvic mass. We compared a false-positive group with a true-negative group of ROMA scores. RESULTS: We analyzed 324 patients using medical records. There were 22 with an epithelial ovarian cancer (EOC), 15 with a borderline ovarian tumor, and 287 with benign disease. Twenty-nine (10.1%) of the patients with benign disease showed high-risk ROMA score (false positive) and 13/37 (35%) patients with EOC, or borderline ovarian tumor showed low ROMA scores (false negatives). The median serum triiodothyronine (T3) level of the false-positive ROMA group in patients with benign disease was lower than in the true-negative ROMA group (p < 0.001) and the estimated glomerular filtration rate (eGFR) was also lower (p = 0.001) in the false-positive ROMA group. Median serum T3 levels in the true-positive ROMA group among patients with EOC, or borderline ovarian tumor were lower than in the false-negative ROMA group (p = 0.043). CONCLUSION: Median serum T3 level and eGFR in the false-positive ROMA group in patients with benign ovarian disease were lower than in the true-negative group.

Hyperreactio Luteinalis (Multiple Luteinized Follicle Cysts): A Report of 10 Cases.

Hyperreactio luteinalis is a rare entity arising in pregnancy and in the setting of gestational trophoblastic diseases (ie choriocarcinoma, molar pregnancy) that presents with, typically, bilateral ovarian enlargement due to numerous follicle cysts. While the phenomenon is benign and spontaneously regresses following delivery or treatment, a specimen may be seen in pathology when oophorectomy or cystectomy is performed to exclude malignancy or to manage acute complications such as torsion. Such resections may exhibit overlapping microscopic features with cystic granulosa cell tumors. We thus reviewed 10 cases of hyperreactio luteinalis in the setting of pregnancy, the largest pathologic cohort to date, to highlight notable features of this disorder. Patients ranged from 22 to 30 yr old. Most patients (n=6) presented at time of cesarean section with incidentally discovered ovarian masses. Three patients presented in the postpartum period, and 1 underwent surgery at 28 wk gestation due to the finding of a unilateral ovarian mass. The ovaries ranged from 8.5 to 29 cm and were multicystic and bilateral in 8 of the cases. Histologic examination demonstrated multiple, variably sized cystic follicles lined by a granulosa cell layer of varying thickness and theca cells with marked eosinophilic cytoplasm. Stromal edema was often prominent, with theca cells occasionally noted in nests, cords, and as single cells in foci of edema. Mitoses were generally seen more often in the granulosa cell layer (mean=2.6 per high power fields) compared with the theca cell layer (mean=1 per 10 high power fields). This series documents the key features of hyperreactio luteinalis that differentiate it from the other benign mass forming lesions encountered in pregnancy, most notably large solitary follicle cyst of pregnancy and puerperium, as well as cystic granulosa cell tumors, especially the juvenile variant, which may also present during pregnancy. Of particular use in differentiating them from juvenile granulosa cell tumor is the absence of pale or vacuolated cytoplasm and solid growth of granulosa cells in cases of hyperreactio luteinalis.

A Multicenter International Temporal and External Validation Study of the Ultrasound-based Endometriosis Staging System.

STUDY OBJECTIVE: The aim of this study was to validate temporally and externally the ultrasound-based endometriosis staging system (UBESS) to predict the level of complexity of laparoscopic surgery for endometriosis. DESIGN: A multicenter, international, retrospective, diagnostic accuracy study was carried out between January 2016 and April 2018 on women with suspected pelvic endometriosis. SETTING: Four different centers with advanced ultrasound and laparoscopic services were recruited (1 for temporal validation and 3 for external validation). PATIENTS: Women with pelvic pain and suspected endometriosis. INTERVENTIONS: All women underwent a systematic transvaginal ultrasound and were staged according to the UBESS system, followed by classification of laparoscopic level of complexity according to the Royal College of Obstetricians and Gynaecologists (RCOG) levels 1 to 3. MEASUREMENTS AND MAIN RESULTS: UBESS I, II, and III were then correlated with RCOG levels 1, 2, and 3, respectively. A comparison between temporal and external sites (skipping "A") and between each site was performed in terms of the diagnostic accuracy of UBESS to predict RCOG laparoscopic skill level. A total of 317 consecutive women who underwent laparoscopy with suspected endometriosis were included. Complete transvaginal ultrasound and laparoscopic surgical outcomes were available for 293/317 (92.4%). At the temporal site, the accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of UBESS I to predict RCOG level 1 were 80.0%,73.8%, 94.9%, 97.2%, 60.2%, 14.5%, and 0.3%, respectively; of UBESS II to predict RCOG level 2 were 81.0%, 70.6%, 82.0%, 26.7%, 96.8%, 3.9%, and 0.3%, respectively; of UBESS III to predict RCOG level 3 were 91.0%, 85.7%, 92.4%, 75.0%, 96.1%, 11.3%, and 0.2%, respectively. At the external sites, the results of UBESS I to predict RCOG level 1 were 90.3%, 92.0%, 88.4%, 90.2%, 90.5%, 7.9%, and 0.1% respectively; UBESS II to predict RCOG level 2 were 89.2%, 100.0%, 88.5%, 37.5%, 100.0%, 8.7%, and 0.0%, respectively; and UBESS III to predict RCOG level 3 were 86.0%, 67.6%, 98.2%, 96.2%, 82.1%, 37.8%, and 0.3%, respectively. When patients requiring ureterolysis (i.e., RCOG level 3) in the absence of bowel endometriosis were excluded (n = 54), the sensitivity of UBESS III to correctly classify RCOG level 3 increased from 85.7% to 96.7% at the temporal site (n = 42) and from 67.6% to 96.0% at the external sites (n = 12) (p <.005). CONCLUSION: The results from this external validation study suggest that UBESS in its current form is not generalizable unless there is either or both bowel deep endometriosis and cul-de-sac obliteration present. The major limitation appears to be the misclassification of women who require surgical ureterolysis in the absence of bowel endometriosis.

Identification of MicroRNAs as Potential Biomarkers in Ovarian Endometriosis.

Endometriosis, as a prevalent gynecological disease, is characterized by the presence of endometrial-like tissue outside the uterus, causing infertility and considerable pain and affecting the quality of life of women. The pathogenic mechanism has not been fully elucidated, and there are no effective biomarkers for endometriosis. In our study, microRNA (miRNA) expression profiling of 10 ectopic endometrial plasma from patients with ovarian endometriosis and 10 normal plasma from healthy controls was analyzed using a microarray. As a result, 114 differentially expressed miRNAs were identified. Among them, 14 miRNAs were significantly downregulated in patients with ovarian endometriosis, which matched the microarray results. The diagnostic value of the 14 downregulated miRNAs in ovarian endometriosis was evaluated by receiver operating characteristic (ROC) curve analysis, and hsa-let-7i-5p showed the highest area under the ROC curve (AUC) with a value of 0.900. The target genes of the 14 miRNAs were predicted by miRWalk2.0, and the genes that were targeted by at least 2 of the 14 miRNAs were analyzed by function enrichment. The target genes were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as microRNAs in cancer, bladder cancer, and endocrine resistance pathways, and the Gene Ontology (GO) terms such as nucleobase-containing compound metabolic process, cellular nitrogen compound biosynthetic process, and heterocycle metabolic process. The identified 14 differentially expressed miRNAs could be potential biomarkers and therapeutic targets for the diagnosis and treatment of endometriosis.

Characteristics and surgical invervention of ovarian torsion in pregnant compared with nonpregnant women.

The aim of our study was to compare the clinical and surgical characteristics of pregnant and nonpregnant women with surgically verified ovarian torsion, as well as the differences among 3 trimesters during pregnancy.We conducted a retrospective study of patients diagnosed with surgically proven ovarian torsion in our hospital from January 2012 to June 2018. The clinical characteristics, surgical procedure, pathologic outcomes, and trimesters of pregnancy were analyzed.Thirty-three pregnant and 72 nonpregnant patients diagnosed with surgically proven ovarian torsion were assessed during the study period. The most common presenting symptom in both groups was abdominal pain (90.2% and 99.0%, respectively). The median time from admission to surgery was shorter in pregnant patients than nonpregnant patients (5.3 compared with 47.7 hours, P < .001). Pregnant patients had a higher number of twists than nonpregnant patients (median of 2 compared with 1, P < .01). Benign cyst was the most common cyst causing ovarian torsion in both groups, and luteum cyst was more common in the pregnant group. The mean size of ovarian cyst in pregnant patients was much smaller in the third trimester than the first and the second trimesters (6.6 ±â€Š2.0, 8.4 ±â€Š2.1and 8.1 ±â€Š1.5 cm, respectively; P = .097). Cystectomy performed in the third trimester was more frequent compared with the other 2 trimesters (77.8%, 26.7%, and 22.2%, respectively; P = .021).Abdominal pain is the most common feature of ovarian torsion. Clinical presentation of ovarian torsion is relatively similar between pregnant and nonpregnant women, and among different trimesters. The tumor size was smaller in the third trimester of pregnancy than the other 2 trimesters of pregnancy. Cystectomy performed in pregnant patients is more during the third trimester compared with the other 2 trimesters.