Borderline Ovarian Tumors Patients Research Articles

P-365 Fertility preservation in patients with borderline ovarian tumors: safety and reproductive outcomes

Abstract Study question Do borderline ovarian tumors (BOT) patients, undergoing controlled ovarian stimulation (COS) face higher recurrence risks, and what are the associated reproductive outcomes? Summary answer Even in advanced-stage or bilateral BOT, COS does not significantly impact recurrence rates. Additionally, COS for fertility preservation(FP)provides a viable option for future reproductive potential. What is known already The primary approach for treating BOTs involves surgical intervention, emphasizing complete tumor removal. Conservative surgery is an option for young women seeking to preserve reproductive potential. However, the recurrence risk following conservative surgery is significant, reaching up to 25%, necessitating repeat surgeries that impact ovarian reserve. Existing evidence on the safety of COS in terms of BOT recurrence remains inconclusive. Concerns about a potential association between COS and tumor progression persist, particularly in advanced-stage and bilateral disease cases. This study address these gaps in knowledge and provide more clarity on the safety of COS in BOT patients. Study design, size, duration A retrospective cohort study was conducted across two tertiary, university-affiliated medical centres: IRCCS San Raffaele Hospital, Milan, Italy, and SHEBA Medical Hospital, Tel-Aviv University, Israel. The study included 165 patients diagnosed with borderline ovarian tumors who underwent conservative surgery between 2012 and 2023. Participants/materials, setting, methods Participants aged 18-42 years with BOT (stages I-III) and undergoing conservative treatment were stratified into two groups: those opting COS for FP(41 patients)and a control group without such intervention (124 patients). COS involved GnRH antagonist random-start protocols utilizing menotropins and/or recombinant FSH. GnRH-agonist or hCG were used for triggering. Oocyte vitrification or fertilization and embryo freezing was performed. Statistical analyses, including Pearson’s chi-square, Fisher’s exact test, T test, and logistic regression, were employed for evaluation. Main results and the role of chance In the course of COS cycles and oocyte retrieval, no complications were observed. Among 165 participants, 33% experienced BOT recurrence over a median of 28.5 months (range: 12.7 to 42.7). Patients with recurrence were younger (29 vs. 32 years, P = 0.04), had advanced-stage (26 vs. 18, p < 0.0001), and bilateral disease (38% vs. 19%, p = 0.01). Of the 41 undergoing COS, 19 experienced recurrence, comparable to the control group (36 patients, p = 0.055). Notably, all COS-related recurrences were BOT histotype, not invasive carcinoma, managed through a second surgery. No significant differences in ovarian stimulation cycles (2.4 vs 1.7, p = 0.7) or retrieved oocytes (11.8 vs 10.6, p = 0.6) were detected between women with and without recurrence. In multivariate analysis, advanced disease significantly increased recurrence odds (aOR=3.7, 95% CI: 1.7-7.9, P < 0.001), while COS did not (aOR=1.7, 95% CI: 0.7-3.9, P = 0.16). This suggests that while age and disease stage play roles, COS alone may not significantly influence recurrence rates. Importantly, among women undergoing COS for FP, 17 achieved at least one pregnancy, totaling 24 pregnancies, with 18 live births. Six were spontaneous, and three used frozen embryos from FP cycles. This underscores the reproductive success of FP through COS, providing hope for fulfilling childbearing desires post-BOT diagnosis. Limitations, reasons for caution Limitations include the retrospective nature, a selection bias in the COS group, and the rarity of the disease leading to a small sample size. Despite these, the recurrence rate in the COS group was comparable to a systematic review, and caution is advised in interpreting these results. Wider implications of the findings Our study suggests that COS does not significantly contribute to recurrence risk in BOT patients, even in advanced stages. FP through COS enhances the likelihood of live births in these patients. While cautious interpretation is warranted, these findings offer hope and call for larger prospective studies to confirm these results. Trial registration number not applicable

Successful pregnancy using immature oocytes retrieved from resected borderline ovarian tumor: a case report and literature review

BackgroundDespite the recent progress of fertility preservation technique, achievement of pregnancy in women with ovarian tumor is still challenging. Here, we report a case of OTO-IVM (ovarian tissue oocyte in-vitro maturation) resulting in a successful delivery.Case presentationThe patient, a 33-year-old woman with a history of left borderline ovarian tumor (BOT) who underwent left salpingo-oophorectomy three years ago, presented with an enlarged right ovary during infertility treatment, indicating the recurrence of BOT. Because the patient disagreed with curative surgery and normal part-preservation surgery, we eventually performed OTO-IVM. A right salpingo-oophorectomy was first performed. Eight immature oocytes were immediately aspirated not only from visible follicles, but also from entire cortex for invisible follicles, of the removed ovary. In addition, IVM procedure generated six mature oocytes, and were subjected to intracytoplasmic sperm injection (ICSI). Accordingly, three embryos were obtained and cryopreserved. Three months after surgery, hormone replacement therapy was initiated, and a frozen-thawed embryo was transferred, resulting in a successful pregnancy. Although a cesarean section was performed at 36 weeks due to maternal ileus, the baby was delivered without complications.ConclusionsThis report indicates this treatment to be an effective approach for fertility preservation in BOT patients, especially, the importance of collecting oocytes from the entire ovarian cortex was suggested.

Evaluation of Borderline Ovarian Tumor Recurrence Rate after Surgery with or without Fertility-Sparing Approach: Results of a Retrospective Analysis.

Borderline ovarian tumors (BOTs) comprise 15-20% of primary ovarian neoplasms and represent an independent disease entity among epithelial ovarian cancers. The present study (Clinical Trial ID: NCT05791838) aimed to report a retrospective analysis of the management and outcomes of 86 consecutive BOTs patients, 54 of which were at a reproductive age. All patients with BOTs undergoing surgical treatment from January 2010 to December 2017 were included. Data were retrospectively reviewed. High levels of Ca-125 were observed in 25.6% of the FIGO stage I patients and 58.3% of the advanced disease patients. Fertility-sparing surgery and comprehensive surgical staging were performed in 36.7% and 49.3% of the patients, respectively. Laparotomy was the most frequent surgical approach (65.1%). The most common diagnosis at frozen sections was serous BOT (50.6%). Serous BOTs have significantly smaller tumor diameters than mucinous BOTs (p < 0.0001). The mean postoperative follow-up was 29.8 months (range 6-87 months). Three patients experienced a recurrence, with an overall recurrence rate of 3.5% (10% considering only the patients who underwent fertility-sparing treatment). BOTs have low recurrence rates, with excellent prognosis. Surgery with proper staging is the main treatment. Conservative surgery is a valid option for women with reproductive potential.

Do Exophytic and Endophytic Patterns in Borderline Ovarian Tumors Have Different Prognostic Implications? A Large Multicentric Experience.

Borderline ovarian tumor (BOT) accounts for 15-20% of all epithelial ovarian tumors. Concerns have arisen about the clinical and prognostic implications of BOT with exophytic growth patterns. We retrospectively reviewed all cases of BOT patients surgically treated from 2015 to 2020. Patients were divided into an endophytic pattern (with intracystic tumor growth and intact ovarian capsule) and an exophytic pattern (with tumor growth outside the ovarian capsule) group. Among the 254 patients recruited, 229 met the inclusion criteria, and of these, 169 (73.8%) belonged to the endophytic group. The endophytic group showed more commonly an early FIGO stage than the exophytic group (100.0% vs. 66.7%, p < 0.001). Furthermore, tumor cells in peritoneal washing (20.0% vs. 0.6%, p < 0.001), elevated Ca125 levels (51.7% vs. 31.4%, p = 0.003), peritoneal implants (0 vs. 18.3%, p < 0.001), and invasive peritoneal implants (0 vs. 5%, p = 0.003) were more frequently observed in the exophytic group. The survival analysis showed 15 (6.6%) total recurrences, 9 (5.3%) in the endophytic and 6 (10.0%) patients in the exophytic group (p = 0.213). At multivariable analysis, age (p = 0.001), FIGO stage (p = 0.002), fertility-sparing surgery (p = 0.001), invasive implants (p = 0.042), and tumor spillage (p = 0.031) appeared significantly associated with recurrence. Endophytic and exophytic patterns in borderline ovarian tumors show superimposable recurrence rates and disease-free survival.

Evaluation of Clinicopathologic Factors and Surgery Management on Borderline Ovarian Tumor Outcomes

Background: Borderline ovarian tumor (BOT) is a tumor most prevalent in young woman with desire to fertility. There are some controversies on the patient characteristic besides to the factors affecting the recurrence rate among different races. Objectives: The aim of this study is to evaluate clinicopathologic features of the tumor to discover the controversies on the topic. Methods: Medical data of the all referred patients to Motahari clinic from January 2010 till October 2020 were recorded. Patient clinicopathologic characteristics affecting on outcome were evaluated. By using SPSS software, data were tested by chi-square and fish exact test. Also, log rank test was used for survival analysis Results: Totally 145 patients were enrolled. 61.4% versus 38.6% of the patients underwent fertility sparing surgery and radical surgery respectively with common characteristics of mostly belong to stage 1A disease (61.8% vs. 66.1%), unilateral (93.3% vs. 89.3%), serous histology (51.7% vs. 66.1%). The characteristics were different in the aspects of age and tumor size. In the aspect of recurrence rate, higher FIGO stage, younger age, tumor size less than 10cm, performing laparoscopy and fertility sparing surgery were with higher rate of recurrence (P-value &lt; 0.05) while histology type of the tumor, lateralization, micropapillary, microinvasion, noninvasive peritoneal implants, receiving adjuvant chemotherapy and performing lymphadenectomy were not statistically significant for recurrence (P-value &gt; 0.05). Two patients had malignant transformation. Conclusions: Fertility sparing surgery was with more recurrence rate in borderline ovarian tumor patients. However, micropapillary, microinvasion were not significantly with higher recurrence rate in our study but they are challenging issues in border line ovarian tumors among different studies. Due to most prevalence of border line ovarian tumors in young women and desire of fertility preservation, we should notice more to clinicopathologic and surgery types affecting on recurrence of BOTs.

Prognosis and fertility outcomes of patients with borderline ovarian tumors after fertility-sparing surgery

Objective: To explore the clinical prognosis and fertility outcomes in patients with borderline ovarian tumors (BOT) who underwent fertility-sparing surgery, and evaluate the related risk factors. Methods: The study examined the clinicopathological characteristics of 280 patients diagnosed with BOT from Qilu Hospital of Shandong University between January 2009 and December 2019. According to the surgery plan, the patients were divided into the fertility-sparing group (167 cases) and the radical surgery group (113 cases). The information of the patients' age, preoperative serum CA-125 level, surgery method, pathological type, FIGO stage (2014), tumor location, and whether focal canceration combined were collected. The Kaplan-Meier method was used to compare disease-free survival (DFS) between the fertility-sparing surgery group and the radical surgery group. The univariate and multivariate Cox proportional hazard regression analysis was used to explore high-risk factors associated with DFS. Results: A total of 280 BOT patients were identified in the study, with a median age of 35.0 (26.0, 51.0) years old. The median follow-up time was 55.2 (34.7, 79.3)months. 25 patients (15.0%) developed recurrence in the fertility-sparing surgery group, 11 patients (8.7%) developed recurrence in the radical surgery group. There was no significant difference in 5-year DFS rate between the two groups (84.4% vs 90.1%, P=0.223). Only FIGO stage was found to be related to DFS through the univariable and multivariable Cox proportional hazard regression analysis, and patients with FIGO Ⅱ/Ⅲ had higher risk of recurrence [HR (95%CI) 2.872(1.283-6.431)] (P=0.010); Fertility-sparing surgery does not increase the recurrence risk of BOT patients (P=0.116). Pregnancies were reported in 39 patients (54.2%), among whom 37 patients gave birth successfully, and 2 patients selected to terminate pregnancy. Conclusions: The fertility-sparing surgery does not increase the risk of recurrence in BOT patients, and patients who underwent the fertility-sparing surgery have a favorable outcome. FIGO stage is the independent risk factor of DFS in BOT patients.

Clinical features of the microRNA genes methylation in borderline ovarian tumors and depending on the histological structure in ovarian malignancies

Background: Borderline ovarian tumors (BOT) belong to the intermediate type between benign and malignant ovarian neoplasms. Serous borderline tumors share common molecular and genetic characteristics with serous carcinomas. An increase in the methylation level of microRNA (miRNA) genes group has been previously shown during the development and progression of ovarian cancer. However, the study results are contradictory, and their number is not sufficient for a consensus. Current study is the first to search for aberrant methylated genes of the BOT-specific microRNA and for some histological subtypes of ovarian cancer.&#x0D; Materials and methods: The study was based on a set of 99 paired (tumor/healthy) ovarian tumor samples. Methylation analysis was carried out with quantitative methyl-specific polymerase chain reaction (PCR). Screening for BOT biomarkers was performed in 21 genes of miRNA.&#x0D; Results: We have found that some miRNA genes (MIR124-1, MIR125B-1, MIR129-2, MIR132, MIR148A, MIR193A, MIR203A, MIR107, MIR1258, MIR339) were characterized by a high methylation level in the patients with BOT, compared to that in the tissues of healthy women. At the same time, the methylation level in the patients with malignant ovarian tumors (MOT) either differed slightly or was even lower. For the MIR129-2, MIR132, MIR148A, MIR203, MIR107 and MIR1258 genes, a higher level of methylation was detected in the BOT patients, compared to the MOT patients. The methylation level of the MIR148A gene in the BOT patients was 4-fold higher than that in the MOT (31.3% vs 7.9%, p = 0.047, multiple two-sided Kruskal-Wallis test). The methylation levels of the miRNA genes MIR148A and MIR191 were significantly reduced in serous cystadenocarcinoma and increased in serous and endometrioid adenocarcinomas.&#x0D; Conclusion: Methylation of the miRNA MIR148A and MIR191 genes is significantly associated with various histological variants of ovarian cancer. We have shown an increased methylation level of a number of miRNA genes in BOT, compared to MOT. In general, epigenetic factors play a role in the clinical differences between histological forms of ovarian cancer and borderline tumors.

Second fertility-sparing surgery and fertility-outcomes in patients with recurrent borderline ovarian tumors

BackgroundAt the time of recurrence, many borderline ovarian tumor (BOT) patients are still young with fertility needs. The purpose of this study is to evaluate the reproductive outcomes and recurrence rate of second fertility-sparing surgery (FSS) in women with recurrent BOTs.MethodsSeventy-eight women of childbearing age diagnosed with recurrent BOTs from November 2009 to 2020 whose primary treatment was FSS were included.ResultsThe FIGO stage I disease accounted for 46.2% and serous BOT accounted for 87.2% in the study group. Forty-seven patients underwent second FSS, and the remaining 31 underwent radical surgery (RS). Seventeen patients relapsed again after second surgery, but no malignant transformation and tumor-associated deaths were reported. Compared to FIGO stage I, the FIGO stage III tumors were more likely to relapse, but there was no statistical difference in pregnancy rate among patients with different stages. In the second FSS group, recurrence rate was higher in patients who underwent oophorocystectomy compared to patients with unilateral salpingo-oophorectomy (USO), but the pregnancy rate was similar. There was no significant difference in postoperative recurrence risk between USO and RS. The recurrence rate was not associated with operative route (laparoscopy or laparotomy), or lymphadenectomy, or postoperative chemotherapy. Among the 32 patients who tried to conceive, the pregnancy rate was 46.9% and live birth rate was 81.3%.ConclusionUnilateral salpingo-oophorectomy is a safe procedure for FIGO stage I recurrent BOT patients with fertility needs, and can achieve a high postoperative pregnancy rate and live birth rate.

Association of recurrent mutations in BRCA1, BRCA2, RAD51C, PALB2, and CHEK2 with the risk of borderline ovarian tumor

BackgroundThere are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs.MethodsThe study group consisted of 102 patients with histologically confirmed BOT and 1743 healthy controls. In addition, 167 cases with ovarian cancer G1 were analyzed. The analyses included genotyping of 21 founder and recurrent mutations localized in 5 genes (BRCA1, BRCA2, PALB2, RAD51C, and CHEK2). The risk for developing BOT and low-grade ovarian cancer, as well as the association of tested mutations with survival, was estimated.ResultsThe CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03), at an earlier age at diagnosis and about 10% worse rate of a 10-year survival. Mutations in BRCA1 and PALB2 were associated with a high risk of ovarian cancer G1 (OR=8.53, p=0.005 and OR=7.03, p=0.03, respectively) and were related to worse all-cause survival for BRCA1 carriers (HR=4.73, 95%CI 1.45–15.43, p=0.01).ConclusionsResults suggest that CHEK2 (c.470T>C) may possibly play a role in the pathogenesis of BOT, but due to the low number of BOT patients, obtained results should be considered as preliminary. Larger more in-depth studies are required.

Fertility-sparing treatment for serous borderline ovarian tumors with extra-ovarian invasive implants: Analysis from the MITO14 study database

ObjectiveOnly 10–15% of serous borderline ovarian tumors (BOTs) with extra-ovarian disease have invasive implants, and conservative treatments have been rarely reported. The MITO14 is a multi-institutional retrospective study conducted with the aim of systematically collecting data from consecutive BOT patients. The present analysis reports the oncological and reproductive outcomes of women with serous BOT and invasive implants registered into the MITO14 database and conservatively treated between August 2002 and May 2019. MethodsThirteen patients (FIGO2014 stage II–III serous BOT with invasive implants) were recruited. Primary and secondary endpoints were, respectively, recurrence and death rates, and pregnancy and live birth rates. Only patients undergoing fertility-sparing surgery (FSS) were included, while patients were excluded in case of: age > 45 years; second tumor(s) requiring therapy interfering with the treatment of BOT. ResultsMedian follow-up time from primary cytoreduction was 146 months (range 27–213 months). Eleven patients (84.6%) experienced at least one recurrence (median time to first relapse 17 months, range 4–190 months), all of these undergoing secondary surgery (FSS in 7). Five patients attempted to conceive: 3 achieved at least one pregnancy and 2 gave birth at least to a healthy child. At the end of the observation period, all patients were alive with no evidence of disease. ConclusionsFertility-sparing treatment should be considered in a context of serous BOT with invasive implants. Despite the high rate of recurrence, FSS provides good chances of reproductive success without a negative impact on overall survival.

Characteristics Patients with Borderline Ovarian Tumor at Sanglah General Hospital: From Pre- to Post-operative Approach

BACKGROUND: Specific epidemiology data of borderline ovarian tumor (BOT) might be beneficial for the early diagnosis of BOT. The scarcity of BOT epidemiological data in Indonesia urged the writer to study further. AIM: The objectives of the study were to obtain the characteristics of BOT patients in Sanglah General Hospital between 2018 and 2019 according to sociodemographic, hormonal, clinical, and patient outcome factors. METHODOLOGY: This is a descriptive retrospective study. Data were obtained from patient’s medical records at medical records installation Sanglah General Hospital between March 2020 and July 2020. Descriptive data collected from medical records were analyzed using Microsoft Excel 2010 and presented in tables and narrative form. RESULTS: From sociodemographic factors, we found that majority of BOT patients were &gt;40 years old, multiparous women, married, low educated, housewives, and had normal BMI. From hormonal factors, we found that experienced menarche between 11 and 15 years old, most of the patients were already menopause, did not use any contraception. From clinical factors, we found that many were referral cases, with abdominal pain as the main complaint, varied CA 125 and risk of malignancy index levels, unilateral mass, suspected with malignant ovarian cyst when being diagnosed earlier. From patient outcome factors, we found that the majority underwent definitive surgery with no post-operative CA 125 level, no malignant cells on cytology examination, borderline mucinous type in both frozen section and paraffin block examination, and followed up after surgery. CONCLUSIONS: Clinicians could use these characteristics as a reference in diagnosing a patient who fits the profile.

Clinical Characteristics Predict Recurrence in Borderline Ovarian Tumor Patients with Fertility-Preserving Surgery.

PurposeTo identify prognostic factors in patients with borderline ovarian tumor (BOT) and establish and validate a nomogram predicting recurrence in BOT patients treated with fertility-preserving surgery.Patients and MethodsPatients with BOT who underwent surgery at two institutions between January 2000 and June 2017 were included and categorized into training and validation cohorts. Univariate log rank test and Cox regression analysis were performed in the training cohort to identify prognostic factors, and a nomogram was developed to predict the recurrence rate. The model was validated by calculating the C-index and drawing the calibration curve and receiver operating curve (ROC).ConclusionIn the multivariate Cox regression analysis, practice period, past history of benign ovarian disease, past history of benign breast disease, elevated CA125 levels, elevated CA199 levels, surgical methods, greater omentum resection, FIGO stage, postoperative pregnancy, and re-operation were independently associated with recurrence-free survival (p<0.05). The aforementioned prognostic factors were used to develop a nomogram. The nomogram demonstrated a good ability to predict the risk of recurrence (training cohort C-index: 0.866, validation cohort C-index: 0.920). The calibration curve suggested that the predicted recurrence-free survival was closely related to the actual recurrence. ROC analysis showed that the nomogram had a good discriminatory power with the area under curve between 0.776 and 0.956. The nomogram can predict the 1-, 3-, and 5-year recurrence-free survival of BOT patients undergoing fertility-preserving surgery. The predictive model can help guide surgical plans, postoperative monitoring, and prognostic evaluation of BOT patients.

Salpingo-oophorectomy versus cystectomy in patients with borderline ovarian tumors: a systemic review and meta-analysis on postoperative recurrence and fertility

BackgroundTo compare the postoperative recurrence and fertility in patients with borderline ovarian tumors (BOTs) who underwent different surgical procedures: salpingo-oophorectomy versus cystectomy.MethodsPotentially relevant literature from inception to Nov. 06, 2020, were retrieved in databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (Pubmed). We applied the keywords “fertility-sparing surgery,” or “conservative surgery,” or “cystectomy,” or “salpingo-oophorectomy,” or “oophorectomy,” or “adnexectomy,” or “borderline ovarian tumor” for literate searching. Systemic reviews and meta-analyses were performed on the postoperative recurrence rates and pregnancy rates between patients receiving the two different surgical methods. Begger’s methods, Egger’s methods, and funnel plot were used to evaluate the publication bias.ResultAmong the sixteen eligible studies, the risk of recurrence was evaluated in all studies, and eight studies assessed the postoperative pregnancy rates in the BOT patients. A total of 1839 cases with borderline ovarian tumors were included, in which 697 patients (37.9%) received unilateral salpingo-oophorectomy and 1142 patients (62.1%) underwent unilateral/bilateral cystectomy. Meta-analyses showed that BOT patients with unilateral/bilateral cystectomy had significantly higher recurrence risk (OR=2.02, 95% CI: 1.59-2.57) compared with those receiving unilateral salpingo-oophorectomy. Pooled analysis of four studies further confirmed the higher risk of recurrence in patients with cystectomy (HR=2.00, 95% CI: 1.11-3.58). In addition, no significant difference in postoperative pregnancy rate was found between patients with the two different surgical procedures (OR=0.92, 95% CI: 0.60-1.42).ConclusionCompared with the unilateral/bilateral cystectomy, the unilateral salpingo-oophorectomy significantly reduces the risk of postoperative recurrence in patients with BOT, and it does not reduce the pregnancy of patients after surgery.Trial registrationPROSPERO CRD42021238177

Adjuvant therapy of surgical menopause symptoms in rehabilitation of patients with borderline ovarian tumors: a role of “cancer immunotherapy diet”

Aim: to examine intensity of surgical menopause symptoms (postovariectomy syndrome, POES) in patients with borderline ovarian tumors (BOTs) after radical surgery depending on the postoperative period management; to assess a role for “cancer immunotherapy diet”* as a standalone means in correction of surgical menopause symptoms as well as a part of patient-specific rehabilitation program.Materials and Methods. A prospective comparative study was conducted with 62 BOTs female patients aged 30 to 48 (42.0 ± 4.1) years underwent radical surgical treatment, subdivided into 3 groups: group I – “active” rehabilitation (29 subjects underwent 12 month-comprehensive personalized rehabilitation); group II – “passive” rehabilitation (17 women with standard management of the postoperative period in accordance with clinical recommendations); group III – 16 patients followed the one-year “cancer immunotherapy diet” (after being consulted by medical specialist and formulation of individual diet program). Patient data obtained after clinical interview, physical, laboratory and instrumental examinations were assessed at four time points: before surgery (visit 0), after 1, 6 and 12 months (visits 1, 2, 3) after antitumor treatment. In addition, every visit required each patient to fill out the modified Kupperman menopausal index (MMI) questionnaire specifically adapted for BOTs patients. Intensity of neurovegetative, psycho-emotional and metabolic manifestations of surgical menopause symptoms was assessed at various stages of post-surgery period and management strategy during post-surgery period.Results. All BOTs patients one month after radical surgical treatment noted overt signs of surgical menopause. Before surgery, the average MMI score corresponded to normal range – 10.9 (group I), 10.5 (group II), 10.4 (group III), whereas during visit 1 it changed to 37.1, 35.2 and 36.4, respectively evidencing about moderate severity of POES. MMI largely depended on management strategy 6 and 12 months after the onset of therapy: in “active” rehabilitation group it was 27.7 (visit 2) and 22.2 (visit 3), “passive” rehabilitation group – 39.1 (visit 2) and 42.6 (visit 3), “cancer immunotherapy diet” group – 34.1 (visit 2) and 30.8 (visit 3). In addition, distribution of patients based on body mass index (BMI) revealed various types of impaired fat metabolism (IFM) in 59.68 % subjects at visit 0, that increased one month after surgery up to 64.52 %, whereas 6 and 12 months later it decreased down to 62.90 and 61.29 %, respectively. However, end-point results in different groups varied substantially: In particular, at visit 3 in group I 55.17 % (n = 16) subjects had normal BMI, 37.93 % (n = 11) – class I obesity and 6.90 % (n = 2) – class II obesity. The end-point results in group II revealed no patients with normal BMI: 76.47 % (n = 13) and 23.53 % (n = 4) had class I and class II obesity, respectively. Finally, end-point results in group III were at intermediate state: 50.0 % (n = 8) subjects showed normal BMI, whereas 37.5 % (n = 6) and 12.5 % (n = 2) patients demonstrated class I and class II obesity, respectively.Conclusion. Adjuvant therapy of surgical menopause symptoms represents an important component in rehabilitation program for BOTs patients underwent radical surgery. A personalized rehabilitation program demonstrates peak efficacy in correcting surgical menopause symptoms (essential to include “cancer immunotherapy diet” therein). Even isolated administration of diet therapy profoundly reduces intensity of surgical menopause symptoms, thereby improving the quality of woman’s life.

Unilateral cystectomy and serous histology are associated with relapse in borderline ovarian tumor patients with fertility-sparing surgery: a systematic review and meta-analysis

Surgical procedures, histological subtypes, and surgical approaches are involved in the recurrence of borderline ovarian tumors (BOTs), but whether those three factors affect relapse remains controversial. This study aimed to explore the effects of surgical procedures, histological subtypes, and surgical approaches on the relapse and pregnancy rates of BOT after fertility-preserving surgery (FPS) according to the patients' characteristics. A systematic search of PubMed, Embase, and the Cochrane library was conducted from their inception to November 2018. Studies that investigated the impact of surgical procedures, histological subtypes, and surgical approaches on the relapse and pregnancy rates in patients with BOT after FPS were eligible. The pooled odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. Thirty-five studies involving a total of 2921 patients with BOT after FPS were included. The pooled ORs indicated that the risk of relapse was significantly increased in patients who underwent unilateral cystectomy or with serous BOT. There was no significant difference between laparoscopy and laparotomy on the risk of relapse. Surgical procedures, histological subtypes, and surgical approaches did not influence pregnancy rates. Patients who underwent unilateral cystectomy or with serous BOT presented an excess risk of relapse after FPS, but the surgical approach did not affect the risk of relapse. The pregnancy rate is not affected by surgical procedures, histological subtypes, and surgical approaches.

Fertility preservation in borderline ovarian tumor patients and survivors.

Borderline ovarian tumors (BOTs) represent around 15% of all epithelial ovarian cancer. Around one third of those patients is under 40 and has not completed childbearing when the tumor is diagnosed. Cancer survivors are more and more concerned about their future fertility since a large proportion of those with BOTs are young. Whatever the tumor stage, information regarding future fertility after treatment and fertility preservation (FP) options must be delivered to all patients before treatment. A multidisciplinary team will discuss and propose personalized treatment and FP strategies. Nowadays, the FP options offered to patients with BOT are the followings: i) minimal invasive conservative surgery, ii) oocyte cryopreservation after controlled ovarian stimulation (COS) or in vitro maturation (IVM) and iii) ovarian tissue cryopreservation. Generally, the most common strategy to preserve future fertility is represented by minimal invasive conservative surgery. However, with the remarkable success and evolution of assisted reproductive technologies (ART) -notably progress and efficiency in COS and oocyte vitrification -have led to offer another potential approach for FP consisting in oocyte cryopreservation. Several COS protocols, such as random start or dual stimulation associating tamoxifen or aromatase inhibitors with gonadotropins provide similar results when compared to standard protocols while providing safety by minimizing the risk of high estrogen exposure. When COS is contraindicated, oocyte cryopreservation can still be possible throw IVM. Even though, oocyte competence after IVM is lower than that obtained after COS. A less used approach is cryopreservation of ovarian tissue, consisting in freezing ovarian cortex fragments for a future thawing and graft. Some concerns and limitations regard the ovarian cortex graft and the risk of reintroducing malignant cells once performed. Nonetheless, the latter it is the only option in prepubertal patients.

Status quo of uncertainty in illness in patients with borderline ovarian tumors and its influencing factors

Objective To explore the status quo of uncertainty in illness in patients with borderline ovarian tumors (BOT) and its influencing factors. Methods In this cross-sectional study, totally 165 patients with BOT hospitalized in Ningbo Women & Children's Hospital from March 2018 to March 2019 were selected using purposive sampling and investigated with the demographic information questionnaire, the Mishel Uncertainty in Illness Scale for Adult (MUIS-A) and Medical Coping Modes Questionnaire (MCMQ) . Totally 165 questionnaires were distributed, and 150 valid ones were collected, with a recovery rate of 90.9%. Results The total uncertainty of illness score of the 150 patients with BOT ranged 48-107 and averaged (91.32±11.47) . Their total score of coping modes was (45.27±5.32) , among which the score of facing was (19.21±3.75) , accounting for the highest score. There were statistically significant differences in uncertainty in illness scores between BOT patients with different age, marital status, educational background, place of residence, household income, medical payment and those who were familiar with their illness or not (P<0.05) . Multiple linear regression analysis revealed that household income, medical payment, familiar with their own illness or not as well as facing, avoidance and submission were the factors affecting uncertainty in illness (P<0.05) . Conclusions Patients with BOT show uncertainty of illness of different degrees, which is affected by multiple factors. Medical and nursing workers shall reduce patients' uncertainty in illness according to their actualities. Key words: Borderline ovarian neoplasm; Uncertainty in illness; Coping mode; Influencing factor

What women want: Fertility sparing surgery in Borderline ovarian tumours patients and pregnancy outcome

ObjectiveBorderline ovarian tumours (BOTs) are characterized by the presence of cellular proliferation and nuclear atypia without stromal invasion. Compared to malignant ovarian tumours, BOTs have better prognoses. The most important treatment of BOT is surgery. Considering the good prognosis of BOT, fertility-sparing surgery (FSS) can be considered for young women who desire to preserve fertility. Our study evaluated the pregnancy rate in patients with childbearing desire, the efficacy and risk of recurrence of women affected by BOTs who have undergone FSS. Materials and methodsPatients characteristics have been restrospectively retrieved for diagnosis made from June 2000 to December 2017 from San Raffaele Hospital and Policlinico Cagliari. Patients underwent FSS for BOT were interviewed about child wishing and pregnancy outcomes. Results85 patients were recruited for the study. Median age at diagnosis was 33 years. Unilateral salpingo-oophorectomy was performed in 33 patients (38%), unilateral cystectomy in 40 (47%) and 12 underwent both procedures (14%). 40 women (50%) tried to conceive after surgery. The pregnancy rate was 73% and live birth rate was 67%. Childbearing desire and age at diagnosis were significantly associated with the pregnancy rate. ConclusionsConservative surgical treatment seems to be a reasonable therapeutic option for women with BOTs who wish to preserve fertility. Our results suggest that the obstetric outcomes after FSS are promising. Maternal desire and the age of diagnosis are the most important factors affecting PR after surgery. Fertility counselling should be an integral part of the clinical management of women with BOT.

Factors affecting compliance of intraoperative frozen and final histopathology in borderline ovarian tumors: Retrospective cohort study

Aim: Frozen sections (FS) are commonly used in the course of adnexal masses operations, and it assist to select the most appropriate surgical treatment modalities in addition to intraoperative management. In this study, we aimed to investigate the effect of the demographic and obstetric characteristics as well as biochemical findings with the consistency of intraoperative FS findings with the final histopathological diagnosis in patients with borderline ovarian tumors (BOT).Methods: This retrospective study included a total of 31 BOT patients who underwent intraoperative frozen histopathological study. The study population was divided into two groups; group 1 consisted of patients who had a positive concordance between the findings of intraoperative FS and the final histopathology, while the patients included in the group 2 had a negative concordance between the results of two examinations. We compared two groups in terms of baseline characteristics, tumor markers, tumor size, bilaterality, menopausal status and presence of ascites.Results: There were no statistically significant differences between the two groups in terms of age, body-mass index, tumor markers (CA125, CA19-9, CEA, AFP, CA15-3, β-HCG) and tumor size (P=0.74, P=0.55, P=0.87, P=0.55, P=0.24, P=0.33, P=0.70, P=0.32 and P=0.98, respectively). Also, the presence of bilateral BOT and ascites as well as menopausal status were not different between both groups (P=0.12, P=0.60, P=0.70, respectively).Conclusion: Based on the study findings, we noted that patients whether had concordance or discordance with the findings of intraoperative frozen sections and the final histopathology did not differ in terms of baseline characteristics and tumor markers.

Metalloproteinases at the surface of small extrcellular vesicles in advanced ovarian cancer: Relationships with ascites volume and peritoneal canceromatosis index

Metalloproteinases and their extracellular matrix metalloproteinase inducer (EMMPRIN) play an essential role in the regulation of signaling from growth factors receptors and adhesion molecules, cell motility and extracellular matrix degradation. The aim of the study was to evaluate the relationship between the levels of small extracellular vesicles (sEVs) metalloproteinases, such as ADAM10, ADAM17, MMP2, MMP9 and EMMPRIN and ascites volume and peritoneal canceromatosis index in advanced ovarian cancer patients (OCPs).The subpopulations of metalloproteinases at the surface of sEVs of borderline ovarian tumor patients (BOTPs) (n = 20, 36.5 ± 2.5 years) and previously untreated advanced OCPs (n = 35, 56.5 ± 2.5 years) were evaluated using flow cytometry. The metalloproteinase subpopulations of CD9-positive sEVs isolated from plasma of BOTPs and OCPs appeared to be quite similar. However, a significant difference in the expression of ADAM-metalloproteinases in ascites sEVs was found between BOTPs and OCPs. The level of sEVs metalloproteinases in OCPs significantly depended on the ascites volume. A statistically significant relationship between the level of ADAM10+/ADAM17- subpopulation in plasma sEVs and the peritoneal canceromatosis index was found (R = 0.66, p < .05). The levels of metalloproteinases and EMMPRIN in circulating sEVs, as well as the assessment of individual subpopulations may be promising approaches to OCPs managing.