[External validation of nomogram for the prediction of recurrences of pregnancy-associated breast cancer]. / Cancer du sein associé à la grossesse : validation d'un nomogramme prédictif de la récidive.

OBJECTIVE: Diagnosis and therapeutics are challenging in pregnancy-related breast cancer and a multidisciplinary approach is therefore essential. A nomogram predictive of recurrence at 36 months of PABC has recently been developed, the aim was to evaluate it on an independent cohort. PATIENTS AND METHODS: This was a monocentric retrospective study including all patients with PABC between January 2004 and March 2018. A Kaplan-Meier method was used for the analysis of recurrence-free survival. Nomogram performance was analysed on 3 indicators: discrimination by a receiver operator characteristic curve (ROC), calibration and net clinical benefit by a decision curve analysis. RESULTS: Forty-one patients have been included. The survival rate was 83 % at 3 years. The nomogram showed acceptable discrimination capacities on receiver-operator characteristic analysis (c-index: 0.78). Decision-curve analysis showed a positive net-benefit for relapse probability ranges between 5 % and 35 %. CONCLUSION: The performance of this prediction model is acceptable but the net clinical benefit low. In conclusion, prediction of recurrence remains challenging with a continued need for more precise tools.

Paget's disease of the vulva: A challenge for the gynaecologist.

Paget's disease of the vulva is a rare form of extramammary Paget's disease mainly affecting postmenopausal women. Its pathophysiology remains largely unknown. Up to fairly recently, the only treatment for this disease was surgery, often mutilating the vulva, with significant psychosexual repercussions without the assurance of complete therapeutic efficacy. New therapeutic approaches -topical treatments, radiotherapy or chemotherapy- have emerged in recent years but lack consensual guidelines. We present a literature review of the recent results published in this field.

Borderline ovarian tumors: Guidelines from the French national college of obstetricians and gynecologists (CNGOF).

It is recommended to classify Borderline Ovarian Tumors (BOTs) according to the WHO classification. Transvaginal and suprapubic ultrasonography are recommended for the analysis of an ovarian mass (Grade A). In case of an undetermined ovarian lesion on ultrasonography, it is recommended to perform a pelvic MRI (Grade A) with a score for malignancy (ADNEX MR/O-RADS) (Grade C) included in the report and to formulate a histological hypothesis (Grade C). Pelvic MRI is recommended to characterize a tumor suspected of being BOT (Grade C). It is recommended to evaluate serum levels of HE4 and CA125 and to use the ROMA score for the diagnosis of indeterminate ovarian mass on imaging (grade A). If there is a suspicion of a mucinous BOT on imaging, serum levels of CA 19-9 may be proposed (Grade C). For Early Stages (ES) of BOT, if surgery without risk of tumor rupture is possible, laparoscopy with protected extraction is recommended over laparotomy (Grade C). For treatment of a bilateral serous ES BOT with a strategy to preserve fertility and/or endocrine function, bilateral cystectomy is recommended where possible (Grade B). For mucinous BOTs with a treatment strategy of fertility and/or endocrine function preservation, unilateral salpingo-oophorectomy is recommended (grade C). For mucinous BOTs treated by initial cystectomy, unilateral salpingo-oophorectomy is recommended (grade C). For serous or mucinous ES BOTs, routine hysterectomy is not recommended (Grade C). For ES BOTs, lymphadenectomy is not recommended (Grade C). For ES BOTs, appendectomy is recommended only in case of a macroscopically pathological appendix (Grade C). Restaging surgery is recommended in cases of serous BOTs with micropapillary architecture and an incomplete abdominal cavity inspection during initial surgery (Grade C). Restaging surgery is recommended for mucinous BOTs after initial cystectomy or in cases where the appendix was not examined (Grade C). If restaging surgery is decided for ES BOTs, the following procedures should be performed: peritoneal washing (grade C), omentectomy (grade B), complete exploration of the abdominal cavity with peritoneal biopsies (grade C), visualization of the appendix and appendectomy in case of a pathological macroscopic appearance (grade C) as well as unilateral salpingo-oophorectomy in case of a mucinous BOT initially treated by cystectomy (grade C). In advanced stages (AS) of BOT, it is not recommended to perform a lymphadenectomy as a routine procedure (Grade C). For AS BOT in a patient with a desire to fall pregnant, conservative treatment involving preservation of the uterus and all or part of the ovary may be proposed (Grade C). Restaging surgery aimed at removing all lesions, not performed initially, is recommended for AS BOTs (Grade C). After treatment, follow-up for a duration greater than 5 years is recommended due to the median recurrence time of BOTs (Grade B). It is recommended that a systematic clinical examination be carried out during follow-up of a treated BOT (Grade B). If the determination of tumor markers is normal preoperatively, the routine dosage of tumor markers in BOT follow-up is not recommended (Grade C). In case of an initial elevation in serum CA 125 levels, it is recommended to monitor CA 125 during follow up (Grade B). In case of conservative treatment, it is recommended to use transvaginal and transabdominal ultrasound during follow up of a treated BOT (Grade B). In the event of a BOT recurrence in a woman of childbearing age, a second conservative treatment may be proposed (Grade C). A consultation with a physician specialized in Assisted Reproductive Technique (ART) should be offered in the case of BOTs in women of childbearing age (Grade C). When possible, a conservative surgical strategy is recommended to preserve fertility in women of childbearing age (Grade C). In the case of optimally treated BOT, there is no evidence to contraindicate the use of ART. The use of hormonal contraception after serous or mucinous BOT is not contraindicated (Grade C). After management of mucinous BOT, for women under 45 years, given the benefit of Hormonal Replacement Therapy (HRT) on cardiovascular and bone risks, and the lack of hormone sensitivity of mucinous BOTs, it is recommended to offer HRT (Grade C). Over 45 years of age, HRT can be prescribed in case of a climacteric syndrome after individual benefit to risk assessment (Grade C).

Vulvar intraepithelial neoplasia: Classification, epidemiology, diagnosis, and management.

Vulvar intraepithelial neoplasia (VIN) is classified into two entities: differentiated (dVIN) and vulvar high-grade squamous intraepithelial lesions (vH-SIL). dVIN is a premalignant lesion that develops on an existing vulvar lesion such as lichen sclerosus, while vH-SIL is associated with HPV infection. The two entities differ in terms of pathophysiology, background, prognosis, and management. The incidence of VIN in young women is rising and recurrence is common, even after radical surgery, which can cause significant disfigurement. Alternative strategies include topical treatments, ablation, and a watch-and-wait approach. There is currently no consensus on how these lesions should be managed. We review the literature in this field.

[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 - Value of Tumor Markers]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Pertinence des marqueurs tumoraux.

OBJECTIVES: To evaluate the diagnostic value of serum biomarkers in the management strategy of borderline ovarian tumours (BOT) to make management recommendations. METHODS: English and French review of literature from 1990 to 2019 based on publications from Pubmed, Medline, Cochrane, with keywords: borderline ovarian tumors, tumour markers, CA125, CA19 9, ACE, CA72 4, TAG72, HE4, ROMA, mucinous, serous, mucinous, endometrioid ovarian tumours, peritoneal implants, recurrence, overall survival, follow-up. Among 1000 references, 400 were selected and only 30 were screened for this work. RESULTS: Literature review: there is low evidence in literature concerning the discriminating value of serum tumour biomarkers (CA125, CA19-9, CEA, CA72-4, HE4) and specific score between presumed benign ovarian tumour/BOT/ovarian cancer (LE4). Serum CA125 antigen is higher in case of serous borderline ovarian tumour (LE4), increase with the tumor height, the FIGO stage, notably in case of serous borderline ovarian tumor. However, a normal value rate of serum CA125 antigen does not rule out a BOT (LE4). The preoperative positivity rate of CA19 9 in case of TFO is relatively lower than that of CA125 and is higher in mucinous TFO. The preoperative rate of serum CA19 9 antigen increases with the tumour height and the FIGO stage (LE4) and are higher in case of mucinous BOT (LE4). Preoperative rates of serum HE4 are not different between histologic type of BOT. A high level of serum biomarkers (CA125) is a predictive factor of peritoneal implants (LE4) and an independent predictive factor of recurrence (CA125) (LE4). RECOMMENDATIONS: no recommendation can be made about the use of serum tumour biomarkers (CA125, CA19-9, CEA, CA72-4, HE4) or specific score in order to distinguish benign ovarian tumor/borderline ovarian tumor/ovarian cancer in case of indeterminate mass. In case of suspicion of mucinous ovarian tumour on imaging, the systematic dosage of serum CA19-9 antigen can be proposed (grade C). In case of an ovarian indeterminate mass on imaging; dosage of serum HE4 and C125 is recommended. If preoperative dosage of serum tumor biomarkers is normal, their systematic dosage is not recommended in the follow-up of BOT (grade C). If preoperative dosage of CA125 is high, the systematic dosage of CA125 is recommended in the follow-up of BOT with no precisions about the rhythm and the duration of the follow-up (grade B).

[Robotic surgery program in gynecology: Lessons from the first 100 procedures]. / Implantation d'un programme de chirurgie robotique gynécologique : leçons à retenir des 100 premières procédures.

INTRODUCTION: The objective of this work is to report the first 6 months of a robotic program in a surgical gynecological team, trained in advanced laparoscopy, in terms of operating times, complication rate, analgesic consumption and average duration of hospitalization. METHODS: This is a prospective observational study, intended to treat. RESULTS: During the study period, 98 women underwent laparoscopic robot assisted surgery. The average BMI was 27.2kg/m2 (±7). Malignant diseases accounted for 41% of operative indications. Comparing the first 30 procedures to the last 30 procedures, there is a significant decrease in docking times: 14.7min (±7.0) vs 8.9min (±5.0), P=0.009. There is also a trend towards a decrease in operative times for hysterectomy: 151.9min (±56.2) vs 113min (±51.4), P=0.08. The rates of complications were not significantly different at the beginning and end of inclusion during the study (10.0% vs 16.7%). CONCLUSION: The implementation of a robotic surgery program in a gynecological surgery department does not lead to an increase in complications for the patients, including for the first procedures. The learning curve mainly allows a reduction in the robot's installation time.

Management and prognosis of pure primary squamous cell carcinoma of the breast.

PURPOSE: The aim of the study was to investigate the management and prognosis of Pure primary squamous cell carcinoma (PPSCC) of the breast. MATERIALS AND METHODS: This study is a multicentre retrospective cohort from three French tertiary referral hospitals (Rennes, Orléans and Tours) including all women treated for a PPSCC of the breast defined by squamous cells that could contain a minority of sarcomatoid component. We excluded carcinomas with a ductual component. Clinicopathologic, radiological and therapeutic patterns were described. Demographic, histological and therapeutic characteristics were compared to a population of women with triple negative invasive breast carcinomas. RESULTS: Twelve patients were included, with a mean age of 71.6 years. All lesions were unifocal, with a cystic complex ultrasound mass in 50% of cases. Mean tumor size was 43mm, with axillary lymph node metastasis in 25% of patients. The comparison with a population of women with triple negative breast carcinomas revealed that women with PPSCC were older (71 versus 57 years, p=0.003), tumor size was larger (43mm versus 25mm, p=0.032) and local recurrence occurred earlier (three months versus 38 months, p=0.014). CONCLUSION: PPSCC is a rare entity with a worse prognosis in comparison with triple negative invasive carcinoma.

Bicyclist's vulva: Diagnostic and therapeutic aspects.

The authors report a case of a rare vulvar condition in a young cyclist, known as bicyclist's vulva. The diagnosis was based on the clinical context (intensive cycling training with repeated saddle sores, responsible for painless unilateral swelling of the labium majus to a significant size and functional discomfort). Imaging examinations were used to characterize the lesion and its relationship with the pelvic organs. The lesion was composed of connective tissue, poorly demarcated and heavily collagenised without necrotic or hemorrhagic areas. Large cicatricial collagen bundles were observed. The fibroblasts revealed no atypia and just a few scattered undilated vessels ere noted. Special staining did not reveal any amyloid deposits. A complementary immunohistochemical analysis with anti-CD 34 antibody showed vascularization that was homogeneous and morphologically normal. The treatment was surgery, and in our case the cosmetic and functional impact of wide surgical excision of the lesion was improved by in situ injection of autologous fat. The pathology findings enabled us to rule out other perineal tumors such as aggressive angiomyxoma of the vulva and to describe the lesion microscopically.

Prospective Assessment of First-Year Quality of Life After Pelvic Exenteration for Gynecologic Malignancy: A French Multicentric Study.

BACKGROUND: Pelvic exenteration remains one of the most mutilating procedures, with important postoperative morbidity, an altered body image, and long-term physical and psychosocial concerns. This study aimed to assess quality of life (QOL) during the first year after pelvic exenteration for gynecologic malignancy performed with curative intent. METHODS: A French multicentric prospective study was performed by including patients who underwent pelvic exenteration. Quality of life by measurement of functional and symptom scales was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0) and the EORTC QLQ-OV28 questionnaires before surgery, at baseline, and 1, 3, 6, and 12 months after the procedure. RESULTS: The study enrolled 97 patients. Quality of life including physical, personal, fatigue, and anorexia reported in the QLQ-C30 was significantly reduced 1 month postoperatively and improved at least to baseline level 1 year after the procedure. Body image also was significantly reduced 1 month postoperatively. Global health, emotional, dyspnea, and anorexia items were significantly improved 1 year after surgery compared with baseline values. Unlike younger patients, elderly patients did not regain physical and social activities after pelvic exenteration. CONCLUSIONS: Therapeutic decision on performing a pelvic exenteration can have a severe and permanent impact on all aspects of patients' QOL. Deterioration of QOL was most significant during the first 3 months after surgery. Elderly patients were the only group of patients with permanent decreased physical and social function. Preoperative evaluation and postoperative follow-up evaluation should include health-related QOL instruments, counseling by a multidisciplinary team to cover all aspects concerning stoma care, sexual function, and long-term concerns after surgery.

[Pap Smear after 65 years]. / Pratique du frottis cervicovaginal après 65 ans.

The French recommendations (in favor of stopping cervical cancer screening by cervico-uterine smear from 65 years of age) are logical in the context of organized screening; however, it is not yet generalized in France. The proportion of invasive cervical cancer in the oldest patients is high and these cancers are more evolved and have a more pejorative prognosis. The prevalent infection with high-risk HPV virus remains important in elderly patients: if the HPV infection does not appear to be more risky in the elderly, HPV-induced lesions appear to be more evolving. Unfortunately, pap smear coverage rates are low in the most advanced age groups. Patients without adequate follow-up are exposed to invasive cancer after age 65: all studies insist on the protective effect of two or more normal pap smears between 50 and 65 years that would allow to stop screening. Recent publications in Europe insist, however, on the value of continuing screening beyond the age of 65 in populations that live longer. For the clinician, in France, patients who could benefit from systematic FCU after age 65 could be those: (1) who request it, (2) who have an HPV history, (3) who have not had more than 3 consecutive normal pap smears or (4) who have an associated pathogenic condition. The place of the HPV test deserves to be considered: because of its very high negative predictive value, it could be performed as an exit test or as an alternative test to the pap smear.

Evaluation of adherence to French clinical practice guidelines in the management of pregnancy loss issued by the French College of Obstetricians and Gynecologists, one year after publication: A vignette-based study.

OBJECTIVES: To assess the adhesion of French obstetricians and gynecologists to the French clinical practice guidelines for pregnancy loss, issued by the French College of Obstetricians and Gynecologists, one year after publication. METHODS: An online vignette-based study was emailed to a sample of French obstetricians and gynecologists to compare their management of women with missed early miscarriage and incomplete early miscarriage. A descriptive statistical analysis was performed comparing the rates of appropriate management for these two indications before and after the release of the guidelines. RESULTS: Of the 404 specialists contacted, 143 completed the questionnaire. Forty-three percent stated that they had changed their practices following the release of the guidelines. The rate of adhesion was moderate for the management of missed early miscarriage (53% after publication of the guidelines versus 42% before, P=0.001) with a trend to avoid watching-and-waiting management. The rate of adhesion was poor for the management of incomplete early miscarriage (43% after the publication of the guidelines versus 27% before, P<0.001) with a lower use of misoprostol. CONCLUSION: Adhesion to the French guidelines appears to be moderate for the management of missed early miscarriage and low for the management of incomplete early miscarriage.

Patterns of care and the survival of elderly patients with high-risk endometrial cancer: A case-control study from the FRANCOGYN group.

BACKGROUND: The standard of care of endometrial cancer involves complex procedures such as pelvic and para-aortic lymphadenectomy and omentectomy, particularly for high-risk endometrial cancer. Few data are available about these complex surgical procedures and adjuvant therapy in elderly women. We aim to examine treatment and survival of elderly women diagnosed with high-risk endometrial cancer. STUDY DESIGN: We performed a case-control study of women diagnosed between 2001 and 2013 with high-risk endometrial cancers. Women older than 70 years (n = 198) were compared with patients <70 years (n = 198) after matching on high-risk for recurrence and LVSI status. RESULTS: Elderly patients had lymphadenectomies less frequently compared with younger patients (76% vs 96%, p < 0.001) and no adjuvant treatment more frequently (17% vs 8%, p = 0.005) due to less chemotherapy being administered (23% vs 46%, p < 0.001). The 3-year DFS, CSS and OS of patients ≥70 years was 52% (43-61), 81% (74-88) and 61% (53-70), respectively. These were significantly lower than the 3-year DFS, CSS, and OS of younger patients, which was 75% (68-82) (p < 0.001), 92% (87-96) (p < 0.008) and 75% (69-82) (p = 0.018), respectively. Cox proportional hazard models found that elderly women had 57% increased risk of recurrence (hazard ratio 1.57, 95% CI 1.04-2.39) compared with younger patients. CONCLUSION: Although we found an independently significant lower DFS in elderly patients with high-risk endometrial cancer when compared with young patients, elderly women are less likely to be treated with lymphadenectomy and chemotherapy. Specific guidelines for management of elderly patients with high-risk endometrial cancer are required to improve their prognosis.

[Pap smear before 25 years old]. / La pratique du frottis cervico-vaginal avant 25 ans.

OBJECTIVES: Current French recommendations advocate cervical-vaginal screening for cervical cancer from age 25 whereas earlier screening is mostly found in current clinical practice although its consequences are not well understood. METHODS: A literature review using the MedLine database on the natural history of HPV infections, cytological screening, management of cytological and histological anomalies in adolescents and young women. RESULTS: The adolescent and young woman have some characteristics that distinguish them from adult women: a high prevalence of HPV infections (making the use of the HPV test unprofitable), accompanied by a higher clearance; frequency of minor cytological abnormalities (for which a cytological surveillance without colposcopy is sufficient) and low-grade histological lesions of low grade the usual prognosis of which is complete recovery; and rarity of CIN3 lesions and absence of invasive lesions, allowing no treatment in patients with CIN2 lesions and compliant to cytological and colposcopic surveillance. CONCLUSION: Cervical screening in the adolescent and young woman is not a logical attitude and the discovery of cytological or histological lesions requires specific behavior in this particular population.

Impact of the French 3rd and 4th generation pill scare in women seeking termination of pregnancy.

INTRODUCTION: The aim of this study was to evaluate changes in the contraceptive profile of women seeking termination of pregnancy following the debate on 3rd and 4th generation pills in France in 2012. MATERIALS AND METHODS: Single-center case-control study comparing the attitude to contraception before (between 02/15/2012 and 07/16/2012) and after the debate (between 02/25/2013 and 06/24/2013). RESULTS: A total of 291 patients consulted before and 601 after the debate. We showed that there were more students (+9.5%), more single women (+8.3%) and fewer working women (-7.7%) in the cohort after the debate. After the termination procedure, prescriptions for long-acting reversible contraceptive (LARC) methods increased (+7.8%, P=0.03), in particular in patients aged 25 or younger, including nulliparous (+12.6%, P=0.02). CONCLUSION: The media alert about the pill led to a change in the contraceptive standard in the post-abortion period and altered patient profiles. An increase was notably observed in certain vulnerable populations (high school students, unemployed and single women). It remains to be seen whether these changes are transient or permanent.

[Can new molecular profiles in epithelial ovarian cancer modify therapeutics?] / Les nouveaux profils moléculaires dans le cancer de l'ovaire peuvent-ils modifier les stratégies thérapeutiques ?

Epithelial ovarian cancer (EOC) affects 4500 women a year in France, with a survival of 30% at 5 years. Treatment is based on extensive surgery and chemotherapy. Around 15% of EOCs are due to genetic mutation predisposition essentially with mutated BRCA1 and BRCA2 genes. Four histological subtypes are described (serous, endometrioid, and mucinous cells to clear), corresponding to different carcinogenesis and distinct molecular mutations. High-grade serous EOCs have a mutation of the BRCA genes in 20-30% of cases. This mutation causes a deficit of repair by homologous recombination of DNA in case of double strand break, allowing greater sensitivity to platinum salts and the use of PARP inhibitors, a protein involved in the repair of single-strand breaks of DNA. PARP inhibitors have shown efficacy in patients mutated BRCA but this effectiveness remains to be demonstrated in patients without congenital mutation, but with acquired BRCAness profile EOC. The BRCAness profile is defined by a tumor having a defect in DNA repair counterpart (not limited to BRCA mutation). Molecular definition of BRCAness is still not consensual but is necessary for the use of PARP inhibitors. Gene expression analyses have identified four subgroups of high-grade serous CEO: mesenchymal, proliferative, differentiated and immunoreactive. These four subtypes, not mutually exclusive, although correlated with prognosis, are not yet used in clinical routine.