Borderline tumours of ovary and fertility preservation-Outcomes from a tertiary care center in India.

OBJECTIVE: Borderline ovarian tumors (BOT) are characterized by atypical epithelial proliferation without stromal invasion and majority are diagnosed in women of reproductive age group desirous of fertility preservation. METHODS: A retrospective review of medical records of patients diagnosed with BOT and on regular follow up at the All India Institute of Medical Sciences New Delhi, during a nine-year study period from March 2014 to March 2023 was performed. Surgical treatment was classified as radical or fertility sparing surgery (FSS). Surgical staging was defined as complete, partial or un-staged. RESULTS: Median age of 91 women was 34 years. Follow up period ranged from 4 to 222 months (median 77 months). Among 68 premenopausal women, 31 (46 %) underwent radical surgery and FSS in 37 (54 %) cases. Median time to conception in 29 women with future fertility wishes was 13 months (range, 4 to38 m). Seven of 29 cases (29 %) required ovulation induction. The pregnancy rate was 82.7 % and live birth rate was 80 %. Eight cases (8.7 %) had a recurrence (7- un-staged, 1- partially staged) and median time to recur was 36 months. There was no significant difference in recurrence between cystectomy/oophorectomy. Ovary was the site of recurrence in all surgically salvaged cases except peritoneal cavity in 1 case with mortality. Relapse free survival at 5 and 10 years in FSS and radical surgery group were similar. CONCLUSION: FSS is a safe procedure and should be considered in young patients desirous of future fertility along with a comprehensive peritoneal staging. Reproductive outcomes are excellent.

Borderline ovarian tumors: a retrospective cohort study on single institution experience, practice patterns and outcomes.

Borderline ovarian tumours (BOTs) commonly affect young nulliparous women, thus making fertility-preserving approaches more desirable. Women who opt for conservative management should be counselled about disease recurrence. In this retrospective study, the medical records of 57 women with BOT treated at the American University of Beirut Medical Centre between January 1986 and May 2018 were reviewed. Clinical, pathologic, and demographic data were collected and analysed to identify variables associated with poor clinical outcomes including advanced disease and risk of recurrence. Younger and nulliparous women were more likely to undergo fertility-sparing surgery. The open approach was adopted for women with larger adnexal masses and was associated with more blood loss with a mean difference of 172 mL (95% CI [110-235], p-value < .001) but no significant difference in operative time and length of hospital stay compared to the laparoscopic approach. CA-125 correlated with an advanced International Federation of Gynaecology and Obstetrics (FIGO) stage (p = .004). The recurrence rate was found to be 7% with a median recurrence time of 41.5 months.IMPACT STATEMENTWhat is already known on this subject? BOTs are common in young nulliparous women who often desire fertility-sparing procedures. Prognostic factors associated with disease severity and recurrence remain controversial.What do the results of this study add? This study presents an opportunity to understand the disease behaviour and compare local practices and outcomes to what was reported in the literature. CA-125 appears to be a useful marker in predicting the stage of BOT.What are the implications of these findings for clinical practice and/or further research? Future research should focus on exploring whether BOTs with micropapillary features represent an aggressive histologic subtype more prone to recurrence.

Fertility Sparing Surgery and Borderline Ovarian Tumours.

To determine the oncological outcomes following fertility-sparing surgery (FSS) for the management of Borderline Ovarian Tumours (BOTs). A retrospective analysis of participants diagnosed with BOTs between January 2004 and December 2020 at the West London Gynaecological Oncology Centre was conducted. A total of 172 women were diagnosed; 52.3% (90/172) underwent FSS and 47.7% (82/172) non-FSS. The overall recurrence rate of disease was 16.9% (29/172), of which 79.3% (23/29) presented as the recurrence of serous or sero-mucinous BOTs and 20.7% (6/29) as low-grade serous carcinoma (LGSC). In the FSS group, the recurrence rate of BOTs was 25.6% (23/90) presenting a median 44.0 (interquartile range (IQR) 41.5) months, of which there were no episodes of recurrence presenting as LGSC reported. In the non-FSS group, all recurrences of disease presented as LGSC, with a rate of 7.7% (6/78), following a median of 47.5 months (IQR 47.8). A significant difference between the type of surgery performed (FSS v Non-FSS) and the association with recurrence of BOT was observed (Pearson Chi-Square: p = 0.000; x = 20.613). Twelve women underwent ultrasound-guided ovarian wedge resection (UGOWR) as a novel method of FSS. Recurrence of BOT was not significantly associated with the type of FSS performed (Pearson Chi- Square: x = 3.166, p = 0.379). Non-FSS is associated with negative oncological outcomes compared to FSS, as evidenced by the higher rate of recurrence of LGSC. This may be attributed to the indefinite long-term follow up with ultrasound surveillance all FSS women undergo, enabling earlier detection and treatment of recurrences.

Clues to the diagnosis of borderline ovarian tumours: An imaging guide.

Borderline Ovarian Tumours (BOTs) are an interesting subset of epithelial neoplasms defined histologically by atypical epithelial proliferation without stromal invasion. These tumours typically affect young women in the reproductive age group and have a good prognosis. Although ultrasonography is the primary screening imaging technique in the evaluation of any suspected adnexal mass, grey-scale and colour Doppler have limited value in characterizing BOTs. Thus, a pelvic magnetic resonance imaging (MRI) is recommended for further characterization on account of its multiplanar capabilities, excellent soft-tissue contrast and high spatial resolution. BOTs histological subtypes display specific features on MRI that are useful in differential diagnosis. However, the final diagnosis and staging of BOTs require pathologic evaluation after surgical excision. Therefore, the purpose of this review is to describe, illustrate and compare the imaging characteristics of the different subtypes of BOTs - serous, mucinous and seromucinous - focusing on MRI, as well as to correlate with pathology findings considering the recent 2020 World Health Organization (WHO) classification, in order to improve the accuracy of preoperative diagnosis and facilitate optimal patient management.

Tumor de Brenner benigno asociado a tumor mucinoso borderline de ovario en paciente postmenopáusica / Benign Brenner tumour associated with a borderline mucinous tumour of the ovary in a post-menopausal patient

El tumor de Brenner es una neoplasia ovárica infrecuente de origen incierto, generalmente asintomática. Su diagnóstico es complejo, sin presentar patrones ecográficos específicos. Se ha asociado a tumores mucinosos con distinto potencial de malignidad, pudiendo encontrar componentes malignos o borderline que determinarán el tratamiento. Para su diagnóstico diferencial es esencial la realización de un estudio inmunohistoquímico, para objetivar el origen clonal del tumor de Brenner y de la estirpe mucinosa. Presentamos el caso de una mujer diagnosticada intraoperatoriamente de un tumor de Brenner asociado a un tumor mucinoso borderline de ovario, en el estudio definitivo posterior.(AU)

Brenner tumour is an uncommon neoplasm of the ovary of uncertain origin and often asymptomatic. Diagnostic is complex, without specific ultrasound patterns. It has been associated with mucinous tumours with different potential for malignancy, and it is possible to find malignant or borderline components that determine the treatment. For its differential diagnosis immunohistochemical study is essential, which shows, according to various studies, a clonal origin of Brenner and mucinous tumour. This is a case report of a Brenner tumour associated with a mucinous tumour, which in a definitive study showed to be associated with a borderline ovarian tumour component.(AU)

Management of borderline ovarian tumours during pregnancy: Results of a French multi-centre study.

OBJECTIVE: To assess the diagnostic and prognostic characteristics of borderline ovarian tumours (BOTs) detected during pregnancy, and to establish an inventory of French practices. MATERIALS AND METHODS: A retrospective multi-centre case study of 14 patients treated for BOTs, diagnosed during pregnancy between 2005 and 2017, in five French pelvic cancerology expert centres, including data on clinical characteristics, histological tumour characteristics, surgical procedure, adjuvant treatments, follow-up and fertility. RESULTS: The mean age of patients was 29.3 [standard deviation (SD) 6.2] years. Most BOTs were diagnosed on ultrasonography in the first trimester (85.7 %), and most of these cases (78.5 %) also underwent magnetic resonance imaging to confirm the diagnosis (true positives 54.5 %). Most patients underwent surgery during pregnancy (57 %), with complete staging surgery in two cases (14.3 %). Laparoscopy was performed more frequently than other procedures (50 %), and unilateral adnexectomy was more common than cystectomy (57.5 %). Tumour size influenced the surgical approach significantly (mean size 7.5 cm for laparoscopy, 11.9 cm for laparoconversion, 14 cm for primary laparotomy; P = 0.08), but the type of resection did not. Most patients were initially diagnosed with International Federation of Gynecology and Obstetrics stage IA (92.8 %) tumours, but many were upstaged after complete restaging surgery (57.1 %). Most BOTs were serous (50 %), two cases had a micropapillary component (28.5 %), and one case had a micro-invasive implant. BOTs were bilateral in two cases (14.2 %). Mean follow-up was 31.4 (SD 14.8) months. Recurrent lesions occurred in two patients (14.2 %) and no deaths have been recorded to date among the study population. CONCLUSION: BOTs remain rare, but this study - despite its small sample size - supports the hypothesis that BOTs during pregnancy have potentially aggressive characteristics.

TERT promoter methylation and protein expression as predictive biomarkers for recurrence risk in patients with serous borderline ovarian tumours.

Epithelial ovarian neoplasms can be divided into three distinct clinicopathological groups: benign, malignant and borderline tumours. Borderline tumours are less aggressive than epithelial carcinomas, with an indolent clinical course and delayed recurrence. However, a subset of these cases can progress to malignancy and relapse, and death from recurrent disease can occasionally occur. Telomerase activation is a critical element in cellular immortalisation and cancer. The enzyme telomerase comprises a catalytic subunit (TERT) expressed in various types of cancers and regulated by promoter methylation mainly in epithelial tumours. The aim of this study was to investigate the promoter methylation status and the expression of TERT in 50 serous borderline tumours (SBTs) and their correlation with clinicopathological features and outcome. TERT methylation was analysed by bisulfite pyrosequencing and TERT expression by immunohistochemistry. Methylation of TERT promoter was only observed in four SBTs. A good correlation with immunostochemistry was found: nuclear positivity for TERT expression was observed in the methylated cases, whereas no expression was detected in unmethylated tumours. One of these patients had a recurrence after 7 years and another patient died from the disease. SBTs with hypomethylated tumours and absence of TERT expression showed a good clinical behaviour. Our study highlights the low presence of TERT methylation in SBTs, confirming that these tumours have a different biology than serous carcinomas. Furthermore, the concordance between TERT promoter methylation and TERT expression and their association with clinical outcomes leads to consider TERT alteration as a potential predictive biomarker for recurrence risk identifying patients who should undergo a careful and prolonged follow-up.

Staging procedures fail to benefit women with borderline ovarian tumours who want to preserve fertility: a retrospective analysis of 448 cases.

BACKGROUND: To evaluate the effect of clinicopathologic factors on the prognosis and fertility outcomes of BOT patients. METHODS: We performed a retrospective analysis of BOT patients who underwent surgical procedures in West China Second University Hospital from 2008 to 2015. The DFS outcomes, potential prognostic factors and fertility outcomes were evaluated. RESULTS: Four hundred forty-eight patients were included; 52 recurrences were observed. Ninety-two patients undergoing FSS achieved pregnancy. No significant differences in fertility outcomes were found between the staging and unstaged surgery groups. Staging surgery was not an independent prognostic factor for DFS. Laparoscopy resulted in better prognosis than laparotomy in patients with stage I tumours and a desire for fertility preservation. CONCLUSION: Patients with BOT fail to benefit from surgical staging. Laparoscopy is recommended for patients with stage I disease who desire to preserve fertility. Physicians should pay more attention to risk of recurrence in patients who want to preserve fertility.

Fertility preservation after fertility-sparing surgery in women with borderline ovarian tumours.

OBJECTIVE: To present a case series of women with borderline ovarian tumours (BOTs) who underwent oocyte vitrification in addition to fertility-sparing surgery. STUDY DESIGN: Observational study of all women referred to a French fertility preservation unit between 2015 and 2019 for counselling regarding a fertility preservation (FP) strategy after BOT fertility-sparing surgery. All eligible women underwent one or more cycles of controlled ovarian stimulation (COS) using an antagonist protocol, followed by oocyte retrieval. Metaphase II (MII) oocytes were vitrified. RESULTS: Twenty-five women with BOTs were referred during the study period. Among them, 11 women underwent at least one cycle of COS. One hundred and seven MII oocytes were vitrified. The mean number of vitrified MII oocytes per woman was 9.7 (standard deviation 5.2). Five live births were reported during follow-up of four women with vitrified oocytes: three spontaneous pregnancies, one in-vitro fertilization cycle with fresh embryo transfer, and one live birth after return of vitrified oocytes. CONCLUSION: Conservative surgery for BOTs offers a high spontaneous pregnancy rate but has a higher risk of relapse than radical treatment. Furthermore, women who undergo conservative BOT surgery have a higher risk of surgery-induced premature ovarian failure. Oocyte cryopreservation after COS appears to be an effective technique after the conservative management of BOTs in women of reproductive age. Although the available short-term data are reassuring, further long-term studies evaluating the safety and cost-effectiveness of this systematic FP strategy after BOT fertility-sparing surgery are required.

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Diagnosis and Management of Recurrent Borderline Ovarian Tumours]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Diagnostic et prise en charge des récidives.

OBJECTIVE: To provide recommendations for the diagnosis and management of the recurrence of Borderline Ovarian Tumour (BOT). METHODS: Literature review by consulting Pubmed, Medline and Cochrane databases. RESULTS: In the case of BOT, most of recurrences are a new BOT without invasive contingent (LE2). In the case of bilateral BOT, bilateral cystectomy is associated with a shorter recurrence time compared to unilateral oophorectomy and contralateral cystectomy (LE2). In recurrent serous BOT, cysts are usually fluid thin-walled with vegetation, corresponding in the IOTA classification to a solid unilocular cyst (LE2). A size of the cyst less than 20mm is not a sufficient to eliminate the diagnosis of recurrent serous BOT (LE2). Recurrence of mucinous BOT predominantly appears as multilocular or as solid multilocular cysts (LE4). In the case of ovarian preservation, recurrences are most often observed on the preserved ovary(s) (LE2). Non-invasive peritoneal recurrence after initial radical treatment including bilateral hysterectomy and adnexectomy is possible, mainly in patients initially diagnosed with stage II or III BOT with non-invasive peritoneal implant (LE3). Most BOT recurrences are asymptomatic, but clinical examination may allow diagnosis of recurrence (LE2). The normality of the CA 125 dosage does not rule out the diagnosis of recurrent BOT (LE2). A second conservative treatment in the event of recurrence of BOT entails the risk of new recurrence (LE2) with no impact on survival (LE4). Totalization of the adnexectomy in case of recurrence of BOT reduces the risk of new recurrence (LE2). Conservative treatment does not increase the risk of recurrence with non-invasive peritoneal implants (LE4). Conservative treatment may be offered after a first non-invasive recurrence in young women who wish to preserve their fertility (gradeC). In the absence of infiltrating tumor, chemotherapy is not indicated. The only cases for which chemotherapy can be considered are those for which there is an infiltrative component in addition to TFO.

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Short Text]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Texte court.

This work was carried out under the aegis of the CNGOF (Collège national des gynécologues et obstétriciens français) and proposes guidelines based on the evidence available in the literature. The objective was to define the diagnostic and surgical management strategy, the fertility preservation and surveillance strategy in Borderline Ovarian Tumor (BOT). No screening modality can be proposed in the general population. An expert pathological review is recommended in case of doubt concerning the borderline nature, the histological subtype, the invasive nature of the implant, for all micropapillary/cribriform serous BOT or in the presence of peritoneal implants, and for all mucinous or clear cell tumors (grade C). Macroscopic MRI analysis should be performed to differentiate the different subtypes of BOT: serous, seromucinous and mucinous (intestinal type) (grade C). If preoperative biomarkers are normal, follow up of biomarkers is not recommended (grade C). In cases of bilateral early serous BOT with a desire to preserve fertility and/or endocrine function, it is recommended to perform a bilateral cystectomy if possible (grade B). In case of early mucinous BOT, with a desire to preserve fertility and/or endocrine function, it is recommended to perform a unilateral adnexectomy (grade C). Secondary surgical staging is recommended in case of serous BOT with micropapillary appearance and uncomplete inspection of the abdominal cavity during initial surgery (grade C). For early-stage serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (grade C). Follow up after BOT must be pursued for more than 5 years (grade B). Conservative treatment involving at least the conservation of the uterus and a fragment of the ovary in a patient wishing to conceive may be proposed in advanced stages of BOT (grade C). A new surgical treatment that preserves fertility after a first non-invasive recurrence may be proposed in women of childbearing age (grade C). It is recommended to offer a specialized consultation for Reproductive Medicine when diagnosing BOT in a woman of childbearing age. Hormonal contraceptive use after serous or mucinous BOT is not contraindicated (grade C).

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Fertility]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Fertilité.

OBJECTIVES: Borderline ovarian tumours (BOT) represent around 15% of all ovarian neoplasms and are more likely to be diagnosed in women of reproductive age. Overall, given the epidemiological profile of BOT and their favourable prognosis, ovarian function and fertility preservation should be systematically considered in patients presenting these lesions. METHODS: The research strategy was based on the following terms: borderline ovarian tumour, fertility, fertility preservation, infertility, fertility-sparing surgery, in vitro fertilization, ovarian stimulation, oocyte cryopreservation, using PubMed, in English and French. RESULTS AND CONCLUSIONS: Fertility counselling should become an integral part of the clinical management of women with BOT. Patients with BOT should be informed that surgical management of BOT may cause damage ovarian reserve and/or peritoneal adhesions. Nomogram to predict recurrence, ovarian reserve markers and fertility explorations should be used to provide a clear and relevant information about the risk of infertility in patients with BOT. Fertility-sparing surgery should be considered for young women who wish preserving their fertility when possible. There is insufficient evidence to claim a causal relation between controlled ovarian stimulation (COS) and BOT. However, in case of poor prognosis factors, the use of COS should be considered cautiously through a multidisciplinary approach. In case of infertility after surgery for BOT, COS can be performed without delay, once histopathological diagnosis of BOT is confirmed. There is insufficient consistent evidence that fertility drugs and COS increase the risk of recurrence of BOT after conservative management. The conservative surgical treatment can be associated to oocyte cryopreservation considering the high risk of recurrence of the disease. In women with BOT recurrence in a single ovary and in women with bilateral ovarian involvement when the conservative management is not possible, other fertility preservation strategies are available, but still experimental.

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Epidemiology and Risk Factors of Relapse, Follow-up and Interest of a Completion Surgery]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Épidémiologie et facteurs de risques de récidive, modalités de surveillance et intérêt d'une chirurgie de clôture.

OBJECTIVE: To provide clinical practice guidelines from the French college of obstetrics and gynecology (CNGOF) based on the best evidence available, concerning epidemiology of recurrence, the risk or relapse and the follow-up in case of borderline ovarian tumor after primary management, and evaluation of completion surgery after fertility sparing surgery. MATERIAL AND METHODS: English and French review of literature from 2000 to 2019 based on publications from PubMed, Medline, Cochrane, with keywords borderline ovarian tumor, low malignant potential, recurrence, relapse, follow-up, completion surgery. From 2000 up to this day, 448 references have been found, from which only 175 were screened for this work. RESULTS AND CONCLUSION: Overall risk of recurrence with Borderline Ovarian Tumour (BOT) may vary from 2 to 24% with a 10-years overall survival>94% and risk of invasive recurrence between 0.5 to 3.8%. Age<40 years (level of evidence 3), advanced initial FIGO stage (LE3), fertility sparing surgery (LE2), residual disease after initial surgery for serous BOT (LE2), implants (invasive or not) (LE2) are risk factors of recurrence. In case of conservative treatment, serous BOT had a higher risk of relapse than mucinous BOT (LE2). Lymphatic involvement (LE3) and use of mini invasive surgery (LE2) are not associated with a higher risk of recurrence. Scores or Nomograms could be useful to assess the risk of recurrence and then to inform patients about this risk (gradeC). In case of serous BOT, completion surgery is not recommended, after conservative treatment and fulfillment of parental project (grade B). It isn't possible to suggest a recommendation about completion surgery for mucinous BOT. There is not any data to advise a frequency of follow-up and use of paraclinic tools in general case of BOT. Follow-up of treated BOT must be achieved beyond 5 years (grade B). A systematic clinical examination is recommended during follow-up (grade B), after treatment of BOT. In case of elevation of CA-125 at diagnosis use of CA-125 serum level is recommended during follow-up of treated BOT (grade B). When a conservative treatment (preservation of ovarian pieces and uterus) of BOT is performed, endovaginal and transabdominal ultrasonography is recommended during follow-up (grade B). There isn't any sufficient data to advise a frequency of these examinations (clinical examination, ultrasound and CA-125) in case of treated BOT. CONCLUSION: Risk of relapse after surgical treatment of BOT depends on patients' characteristics, type of BOT (histological features) and modalities of initial treatment. Scores and nomogram are useful tools to assess risk of relapse. Follow-up must be performed beyond 5 years and in case of peculiar situations, use of paraclinic evaluations is recommended.

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Therapeutic Management of Early Stages]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Prise en charge thérapeutique des stades précoces.

OBJECTIVES: To provide guidelines for clinical practice from the French College of Obstetrics and Gynecology (CNGOF), based on the best evidence available, concerning early stage borderline ovarian tumors (BOT). METHODS: Bibliographical search in French and English languages by consultation of Pubmed, Cochrane, Embase, and international databases. RESULTS: Considering management of early stage BOT, if surgery is possible without a risk of tumor rupture, the laparoscopic approach is recommended compared to laparotomy (Grade C). In BOT, it is recommended to take all the measures to avoid tumor rupture, including the peroperative decision of laparoconversion (Grade C). In BOT, extraction of the surgical specimen using an endoscopic bag is recommended (Grade C). In case of early stage, uni or bilateral BOT, suspected in preoperative imaging in a postmenopausal patient, bilateral adnexectomy is recommended (Grade B). In cases of bilateral BOT and desire of fertility preservation, a bilateral cystectomy is recommended (Grade B). In case of mucinous BOT and desire of fertility preservation, it is recommended to perform a unilateral adnexectomy (Grade C). In case of endometrioid BOT and desire of fertility preservation, it is not possible to establish a recommendation of treatment choice between cystectomy and unilateral adnexectomy. In case of mucinous BOT at definitive histological analysis in a woman of childbearing age who had an initial cystectomy, surgical revision for unilateral adnexectomy is recommended (Grade C). In the case of serous BOT with definitive histological analysis in a woman of childbearing age who has had an initial cystectomy, it is not recommended to repeat surgery for adnexectomy in the absence of residual suspicious lesion during initial surgery and/or on postoperative imaging (referent ultrasound or pelvic MRI) (Grade C). An omentectomy is recommended for complete initial surgical staging when BOT is diagnosed on extemporaneous analysis or suspected on preoperative radiological elements (Grade B). There is no data in the literature to recommend the type of omentectomy to be performed. If restaging surgery is decided for a presumed early stage BOT, an omentectomy is recommended (Grade B). Multiple peritoneal biopsies are recommended for complete initial surgical staging when BOT is diagnosed on extemporaneous or suspected on preoperative radiological elements (Grade C). In case of restaging surgery for a presumed early stage BOT, exploration of the abdominal cavity should be complete and peritoneal biopsies should be performed on suspicious areas or systematically (Grade C). A primary peritoneal cytology is recommended in order to achieve complete initial surgical staging when BOT is suspected on preoperative radiological elements (Grade C). In case of restaging surgery for presumed early stage BOT, a first peritoneal cytology is recommended (Grade C). For early serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (Grade C). For early stage endometrioid BOT, and in the absence of a desire to maintain fertility, hysterectomy is recommended for initial surgery or if restaging surgery is indicated (Grade C). For endometrioid-type early stage BOT, if there is a desire for fertility preservation, the uterus may be retained subject to good evaluation of the endometrium by imaging and endometrial sampling (Grade C). In case of surgery (initial or restaging if indicated) for early stage BOT, it is recommended to evaluate the macroscopic appearance of the appendix (Grade B). In case of surgery (initial or restaging if indicated) for early stage BOT, appendectomy is recommended only in case of macroscopically pathological appearance of the appendix (Grade C). Pelvic and lumbar aortic lymphadenectomy is not recommended for initial surgery or restaging surgery for early stage BOT regardless of histologic type (Grade C). In case of BOT diagnosed on definitive histology, the indication of restaging surgery should be discussed in Multidisciplinary Collaborative Meeting. For presumed early stage BOT, it is recommended to use the laparoscopic approach to perform restaging surgery (Grade C). Restaging surgery is recommended for serous BOT with micropapillary appearance and unsatisfactory abdominal cavity inspection during initial surgery (Grade C). Restaging surgery is recommended in case of mucinous BOT if only a cystectomy has been performed or the appendix has not been visualized, then a unilateral adnexectomy will be performed (Grade C). If a restaging surgery is decided in the management of a presumed early stage BOT, the actions to be carried out are as follows: a peritoneal cytology (Grade C), an omentectomy (there is no data in the literature recommending the type of omentectomy to be performed) (Grade B), a complete exploration of the abdominal cavity with peritoneal biopsies on suspect areas or systematically (Grade C), visualization of the appendix± the appendectomy in case of pathological macroscopic appearance (Grade C), unilateral adnexectomy in case of mucinous TFO (Grade C).

[Borderline Ovarian Tumours: CNGOFS Guidelines for Clinical Practice - Hormonal Contraception and MHT/HRT after Borderline Ovarian Tumour]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Contraception hormonale et THM/THS après tumeur frontière de l'ovaire.

Contraceptive options and menopause management are frequent clinical issues among women previously treated for a borderline ovarian tumour (BOT). OBJECTIVES: To synthesize knowledge on BOT and risk related to hormonal contraception and to menopausal hormone therapy (MHT), and to propose recommendations on contraception and MHT after BOT treatment. METHODS: Systematic review of the literature about hormonal contraception and BOT and on MHT and BOT was conducted on PubMed/Medline and the Cochrane Library. RESULTS: There are no data concerning hormonal contraception after BOT. Current or previous oral contraception is associated with a trend towards decreased risk of serous BOT. Mucinous BOT risk is not or slightly decreased by oral contraception. Hormonal contraception is thus not contraindicated in women previously treated for a BOT (grade C). MHT is associated with a trend towards increased risk of serous BOT. No relation was found between MHT and risk of mucinous BOT. Serous BOTs with high-risk histological criteria (micropapillary pattern, stromal microinvasion or peritoneal implants) are at high-risk of invasive potentially hormone-sensitive recurrence. Hence, caution is needed in the decisions of using MHT after serous BOT with one of these high-risk histological criteria, and MHT should be discussed on a case to case basis. MHT can be prescribed without restriction in women previously treated for mucinous and serous BOT without high-risk histological criteria (grade C). CONCLUSION: Hormonal contraception can be used after BOT. The histological characteristics of the tumour must be taken into account when deciding on the use of HRT/THM.

A systematic review and meta-analysis of the use of ultrasound to diagnose borderline ovarian tumours.

Borderline ovarian tumours (BOTs) are difficult to diagnose preoperatively. The ability to distinguish between BOTs and other ovarian cancer types prior to surgery could have a profound impact on patient childbearing counselling and surgical planning. Ultrasound (US) pattern recognition by an expert examiner can be an excellent tool for the discrimination of benign and malignant ovarian masses. With respect to US features, most studies were based on well-known risk models. Nevertheless, very few studies have solely evaluated the utility of ultrasound in diagnosing BOTs. We aimed to evaluate the use of US in identifying BOTs solely from benign and malignant ovarian tumours in isolation from risk models. We performed a systematic literature review to identify publications that evaluated the use of US to differentiate between BOTs and malignant and/or benign ovarian tumours using Pubmed, Web of Science and the Cochrane Library. We performed a meta-analysis of the diagnostic sensitivity and specificity studies. We computed the summary estimates for sensitivity and specificity of US in diagnosing BOTs using the bivariate approach of Reitsma in the mada package in R. The initial search resulted in 24,737 publications. Hundred and seven publications were screened, and five studies contained diagnostic data. Different US criteria applied to identify BOTs. Four out of five studies including 244 women with BOTs and 965 women with benign or malignant tumours were suitable for the meta-analysis. Pooling of the results from four studies showed an overall sensitivity of 0.660 (95 % CI: 0.597 - 0.718) and specificity of 0.854 (95 % CI: 0.728 - 0.927). The overall US accuracy was uniform in sensitivity and variable in specificity. A low false positive rate, 0.146 (95 % CI: 0.073 - 0.272) was observed. US correctly identified BOTs in more than six out of 10 women for potential ovarian sparing surgery, whereas it correctly identified the absence of BOTs in more than eight out of 10 symptomatic women. More carefully designed studies are needed to evaluate the use of pre-operative US for the diagnosis of BOTs.

Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumours: guidelines from the French national network dedicated to rare gynaecological cancers.

INTRODUCTION: Rare ovarian tumours include complex borderline ovarian tumours, sex-cord tumours, germ cell tumours and rare epithelial tumours. Indications and modalities of fertility preservation (FP), infertility management, contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and experts in reproductive medicine and gynaecology have built guidelines on FP, contraception and menopause hormone therapy in women treated for ovarian rare tumours. MATERIAL AND METHODS: A panel of 35 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review and then rated through two successive rounds. RESULTS: Thirty-five recommendations were identified, concerning indications for FP, contraindications for ovarian stimulation, contraceptive options and menopause hormone therapy for each tumour type. DISCUSSION: Overall, caution has been recommended in the case of potentially hormone-sensitive tumours such as sex-cord tumours, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumours. CONCLUSION: In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.

Oncologic and fertility impact of surgical approach for borderline ovarian tumours treated with fertility sparing surgery.

BACKGROUND: Even if borderline ovarian tumours (BOTs) in young women treated with fertility-sparing treatment (FST) have an excellent outcome, the type of surgery might affect relapse and fertility. We investigated the effect of surgical approach (open surgery vs. laparoscopy) and type of surgery (salpingo-oophorectomy [SO] vs. cystectomy [Cy]) on oncologic and fertility outcomes in patients with BOT. PATIENTS AND METHODS: Patients with BOT treated at San Gerardo Hospital, Monza, with FST in 1978-2013 period were included. Cox models, stratified by decade of surgery, were used to investigate the association between time to first recurrence or conception and clinical factors. RESULTS: Among 535 patients included, 271 underwent unilateral SO and 264 underwent Cy. Median follow-up was 13.5 years. Ten-year (10-yr) recurrence rate was 23% (95% confidence interval [CI]: 18-29%) for SO and 31% (95% CI: 24-38%) for Cy group (P = 0.10) in patients with unilateral tumour, whereas it was 62% (95% CI: 44-79%) and 72% (95% CI: 59-84%), respectively, (P = 0.35) in patients with bilateral tumour. Multivariable analysis showed no association between recurrence and surgical approach (P = 0.44), type of surgery (P = 0.06) and a negative association with advanced stage (hazard ratio [HR] = 3.18; 95% CI: 2.11-4.78; P < 0.001) and bilateral tumours (HR = 2.48; 95% CI: 1.78-3.47; P < 0.001). Among 252 patients (47.1%) with pregnancy desire, multivariable analysis showed no association between conception success and the type of surgery, surgical approach, histology and tumour laterality. Fertility after surgery was positively associated with prior pregnancy (HR = 1.68; 95% CI: 1.17-2.41; P = 0.005) and negatively associated with the number of surgical procedures (HR = 0.62; 95% CI: 0.53-0.73; P < 0.001). CONCLUSIONS: The type of surgical procedures did not influence recurrence rate or fertility. However, additional surgical procedures decreased the fertility potential. These data can support clinicians in tailoring the best strategy for FST in young patients with BOT.

Concomitant endometriosis in malignant and borderline ovarian tumours.

The aim of the study was to reveal the prevalence of concomitant endometriosis in malignant and borderline ovarian tumours. A retrospective analysis was performed of 530 patients with malignant ovarian tumours and 131 with borderline ovarian tumours, who underwent surgery in our hospital between 1995 and 2011. Forty-eight (7.3%) of 661 patients with malignant and borderline ovarian tumours were associated with endometriosis. Of the 48 endometriosis cases, 73% of those were atypical. Infertility was noted in 38% of patients with endometriosis-associated ovarian tumours. The most frequently endometriosis-associated subtypes were endometrioid (33%) and clear cell (18%) histologies. Of endometriosis-associated endometrioid and clear cell ovarian tumours, 70% were early stage and 60% were premenopausal. The prevalence of concomitant endometriosis in borderline tumours (12%) was found to be significantly higher than that found in the malignant ones (6%; p = .02). Of 32 endometriosis-associated malignant ovarian tumours, 69% were FIGO stages I and II. In conclusion, ovarian endometriosis is seen with both malignant and borderline ovarian tumours, the association being significant with borderline tumours. Fortunately, the endometriosis-associated malignant ovarian tumours are mostly early stage. Impact statement What is already known on this subject? Epidemiologic data suggest that endometriosis has malignant potential. However, a subgroup of women with endometriosis at a high risk for ovarian cancer is yet to be clarified. Currently, endometriosis and ovarian cancer association does not seem to have a clinical implication. What do the results of this study add? The findings of this study revealed that nearly 75% of endometriosis-associated ovarian tumours were of atypical endometriosis. Half of endometriosis-associated ovarian tumour cases were of endometrioid/clear cell histology and 70% were early-stage. Endometriosis was significantly associated with borderline ovarian tumours and the endometriosis-associated malignant ovarian tumours were mostly early stage. What are the implications of these findings for clinical practice and/or further research? Additional studies need to be conducted to develop screening approaches for malignant transformation or an association in women with endometriosis. Till that time, a change of current clinical practices cannot be justified. However, counselling and treating women with endometriosis who are at high risk for cancer coexistence or conversion is encouraged.