Prognostic Value and Risk Factors of Peritoneal Carcinomatosis Recurrence for Patients with Endometrial Cancer: A Multicenter Study from the FRANCOGYN Group.

BACKGROUND: The prognosis for patients with endometrial cancer (EC) peritoneal carcinomatosis (PC) recurrence has received little study. This study aimed to determine specific risk factors and prognosis of EC with PC recurrence (PCR) versus no PC recurrence (NPCR). METHODS: Data of all patients with EC who received primary surgical treatment between January 2000 and February 2017 were abstracted from the French FRANCOGYN Research Group database. Clinical and pathologic variables were compared between the two groups (PCR vs. NPCR). Multivariate analysis was performed to define prognostic factors for peritoneal recurrence. Overall survivals (OS) of patients after recurrence were compared using the Kaplan-Meier method. RESULTS: The study analyzed 1466 patients, and 257 of these patients (17.5%) had recurrence. At presentation, 63 of these patients had PC. International Federation of Gynecology and Obstetrics (FIGO) stages 3 and 4 disease were significantly associated with PCR versus NPCR (odds ratio 2.24; 95% confidence interval 1.23-4.07; p = 0.008). The death rate for the patients with PC was 47.6%, with a median survival of 12 months after diagnosis of recurrence. According to the histologic subtype, OS was 29 months (Q1-Q3, 13-NA) for endometrioid carcinomas, 7.5 months (Q1-Q3, 4-15) for serous carcinomas, and 10 months (Q1-Q3, 5-15) for clear cell carcinomas. Chemotherapy for treatment of PCR was associated with improved OS after recurrence (OSAR; p = 0.0025). CONCLUSION: An initial advanced stage of EC is a risk factor for PCR. For women with PCR, a diagnosis of type 1 EC recurrence more than 12 months after the initial treatment and management of PCR with chemotherapy is associated with improved OSAR. Prospective studies are needed to determine the precise optimal management required in this clinical situation and to assess the relevance of biomarkers to predict the risk of PCR for EC patients.

Fertility preservation in women with malignant and borderline ovarian tumors: Experience of the French ESGO-certified center and pregnancy-associated cancer network (CALG).

OBJECTIVE: To describe strategy and results of fertility preservation (FP) in patients with malignant and borderline ovarian tumors. METHODS: Consecutive cohort study of 43 women with malignant or borderline ovarian tumors who underwent FP between February 2013 and July 2019. The study was conducted in national expert center in Tenon University Hospital, Sorbonne University: French ESGO-certified ovarian cancer center and pregnancy-associated cancer network (CALG). Main outcome measure was FP technique proposed by multidisciplinary committee, FP technique used, time after surgery, number of fragments, histology and follicle density (if ovarian tissue freezing), number of expected, retrieved and frozen oocytes (if ovarian stimulation). RESULTS: Pathological diagnosis was malignant epithelial ovarian tumor in five women (11.6%), rare malignant ovarian tumor in 14 (32.6%), borderline in 24 (55.8%), and mostly unilateral (79.1%) and stage I (76.7%). Mean age at diagnosis was 26.8 ± 6.9 years and mean tumor size 109.7 ± 61 mm. Before FP, mean AFC was 11.0 ± 6.1 and AMH levels were 2.7 ± 4.6 ng/mL. Six ovarian tissue-freezing procedures were performed (offered to 13). Twenty-four procedures of ovarian stimulation and oocyte freezing were performed after surgical treatment for 19 women (offered to 28) with a median interval of 188 days. The mean number of mature oocytes retrieved per stimulation was 12.4 ± 12.8. At least 10 mature oocytes were frozen for 52.6% of the women. No FP was offered to five women. CONCLUSION: Oocyte and ovarian tissue cryopreservation should be offered to patients with malignant and borderline ovarian tumors. More data are needed to confirm ovarian stimulation and ovarian tissue grafting safety.

Discoid resection for colorectal endometriosis: results from a prospective cohort from two French tertiary referral centres.

AIM: Using a prospective database of discoid resection performed in two tertiary referral centres, the aim of this study is to assess the feasibility, short-term complication rates and clinical outcomes, including voiding dysfunction, of the procedure. METHOD: A retrospective analysis of a prospective cohort database was conducted from February 2010 to October 2017 in two tertiary referral centres. One hundred and forty-eight consecutive patients scheduled for colorectal endometriosis by discoid resection were enrolled. The median follow-up was 21 months. All the women underwent complete preoperative assessment (MRI, transvaginal ultrasonography and rectal echo-endoscopy) before the removal of colorectal endometriosis. Postoperative complications were classified according to the Clavien-Dindo classification system as minor (grades I and II) or major (grades IIIA, IIIB and IV). Cases of voiding dysfunction were also noted. RESULTS: The procedure was abandoned in seven patients. In 91 (64.5%) of the remaining 141 patients, the diameter of discoid resection removed was ≥ 30 mm. Surgery was performed by laparoscopy in 137/141 cases (92.7%). Grade I-III complications were observed in 37 patients (26.2%) with 11 grade IIIb (7.8%). Postoperative voiding dysfunction occurred in 16 patients (11.3%), 11 of whom required self-catheterization for < 1 month. In a multivariate analysis including age, body mass index, lesion size and history of previous surgery for endometriosis, a history of previous surgery was independently correlated to complication outcome (P = 0.043). CONCLUSIONS: This analysis suggests that discoid resection is associated with good short-term results for women with colorectal endometriosis in a tertiary referral centre as it is associated with a low rate of postoperative complications.

Fertility outcomes in women experiencing severe complications after surgery for colorectal endometriosis.

STUDY QUESTION: What are the fertility outcomes in women wishing to conceive after experiencing a severe complication from surgical removal of colorectal endometriosis? SUMMARY ANSWER: The pregnancy rate (PR) among women who wished to conceive after a severe complication of surgery for colorectal endometriosis was 41.2% (spontaneously for 80%, after ART procedure for 20%). WHAT IS KNOWN ALREADY: While the long-term benefit of surgery on pain and quality of life is well documented for women with colorectal endometriosis, it exposes women to the risk of severe complications. However, little is known about fertility outcomes in women experiencing such severe postoperative complications. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included women who experienced a severe complication after surgery for colorectal endometriosis between January 2004 and June 2014, and who wished to conceive. A total of 53 patients met the inclusion criteria. The fertility outcome was available for 48 women, who were therefore included in the analysis. The median follow-up was 5 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: All the women underwent complete removal of colorectal endometriosis. Postoperative severe complications were defined as grades III-IV of the Clavien-Dindo classification. Fertility outcomes, PR and cumulative pregnancy rate (CPR), were estimated. MAIN RESULTS AND THE ROLE OF CHANCE: Most women experienced a grade IIIb complication (83.3%). Of 48 women, 20 became pregnant (overall PR: 41.2%); spontaneously for 16 (80%) and after ART procedure for 4 (20%). The median interval between surgery and first pregnancy was 3 years. The live birth rate was 14/48 (29.2%). The 5-year CPR was 46%. A lower CPR was found for women who experienced anastomotic leakage (with or without rectovaginal fistula) (P = 0.02) or deep pelvic abscess (with or without anastomotic leakage) (P = 0.04). LIMITATIONS REASONS FOR CAUTION: Due to a lack of information, no sub-analysis was done to investigate other parameters potentially impacting fertility outcomes. WIDER IMPLICATIONS OF THE FINDINGS: The PR for our population was slightly lower to that observed in the literature for women who experience such surgery without consideration for the occurrence of complications. However, 'severe complications' covers a range of conditions which are likely to have a very different impacts on fertility. Even if the PR and CPR appear satisfactory, septic complications can negatively impact fertility outcomes. Rapid ART may be a good option for these patients. STUDY FUNDING/COMPETING INTEREST(S): No funding was required for the current study. Pr H. Roman reported personal fees from Plasma Surgical Inc. (Roswell, GA, USA) for participating in a symposium and a masterclass, in which he presented his experience in the use of PlasmaJet®. None of the other authors declared any conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Maternal and neonatal outcomes in women with colorectal endometriosis.

OBJECTIVE: To evaluate delivery and neonatal outcomes in women with resected or in situ bowel endometriosis. DESIGN: Retrospective cohort study. SETTING: France. POPULATION AND SAMPLE: Analysis of 72 pregnancies from 67 women followed for colorectal endometriosis from 2001 to 2014 in six centres including two university expert centres for endometriosis. METHODS: Univariate analysis of maternal and neonatal outcomes. MAIN OUTCOME MEASURES: Routes for delivery and rate of complications. RESULTS: The colorectal surgery group comprised 41 women and the in situ colorectal group, 26 women. Overall, half of the women underwent caesarean section. A high incidence of postoperative complications (39%) was observed after caesarean section with no difference between the groups. Surgical difficulties at newborn extraction (22%) and postoperative complications (39%) occurred more often in women with anterior deep infiltrating endometriosis (respectively 63 versus 11%, P = 0.007 and 67% versus 26%, P = 0.046) independently of prior surgery for endometriosis. In the remaining half, vaginal delivery required an operative procedure in 28% of the women with a significant increase in postpartum complications compared with those who did not require a procedure (P = 0.001). Overall, the incidence of postpartum complications was lower after vaginal delivery (14%) than after caesarean section (39%) (P = 0.03). CONCLUSION: Pregnant women with colorectal endometriosis, irrespective of prior surgery, should be informed of the high risk of delivery by caesarean section. Vaginal delivery is preferrable in this setting because of the lower incidence of postpartum complications. TWEETABLE ABSTRACT: Due to the incidence of postpartum complications whatever the route of delivery, women should receive level III maternal care.

Prospective, randomized comparison of the use of FloShield Air System® versus the reference technique (water + povidone-iodine solution) during gynecologic endoscopic surgery to evaluate the operative lens vision quality.

BACKGROUND: The FloShield Air System® is a new device for laparoscopic surgery that utilizes a continuous dry CO2 gas flow over the scope to defog the lens and protect it from condensation, debris and smoke. We set out to compare the performance and efficiency of the device in terms of operative lens vision quality (OLVQ) with the reference technique (water + povidone-iodine (PVI) solution) during gynecologic laparoscopic surgery. MATERIALS AND METHODS: We conducted a single-center randomized prospective study between March and June 2016 (Trials Database Registration NCT02702531) including 53 patients undergoing gynecologic laparoscopic surgery with water + PVI solution and 51 patients who underwent surgical procedures with the FloShield Air System. The primary outcome measure was the number of laparoscope removals during surgery. Secondary outcome measures were the time to clean, assessment of the quality of vision, the correlation between the laparoscopic surgical complexity and outcomes, and cost effectiveness. RESULTS: Overall, the mean patient age was 43.2 years (range 22-86) and body mass index 24.8 (range 16.8-42.7). The mean number of endoscope removals during surgery was 7.0 (range 0-37) in the water + PVI solution arm and 2.8 (range 0-12) in the FloShield Air System® arm. The number of removals was significantly lower in the FloShield arm (p < 0.001). No difference in time to clean, quality of vision, level of laparoscopic procedure complexity, or cost was observed between the groups. CONSLUSIONS: The FloShield Air System® resulted in fewer laparoscopic lens removals than the water + PVI solution solution, but that there was no difference in quality of vision, cleaning time or cost, especially for the more complex surgery.

Selective progesterone receptor modulators: current applications and perspectives.

Selective progesterone receptor modulators (SPRMs) are steroid progesterone receptor ligands able to induce agonistic or antagonistic activities. Mifepristone, the class leader, was primarily used for pregnancy termination from the 1980s. Emergency contraception with extended activity was the second major development 30 years later, with mifepristone in some countries and ulipristal acetate world-wide. More recently, ulipristal acetate was released for the treatment of myoma-related uterine bleeding. In addition to a very rapid cessation of bleeding, SPRMs allow a decrease in myoma volume, as do gonadotropin releasing hormone analogs. However, estradiol secretion is not blunted by SPRMs. This offers new alternatives for myoma treatment, especially in women close to menopause. In conclusion, use of SPRMs has allowed significant progress in emergency contraception and treatment of myoma-related symptoms. Numerous future perspectives in women's health care are currently under evaluation.

Call for Surgical Nodal Staging in Women with ESMO/ESGO/ESTRO High-Intermediate Risk Endometrial Cancer: A Multicentre Cohort Analysis from the FRANCOGYN Study Group.

BACKGROUND: The European Society of Medical Oncology (ESMO)/European Society of Gynaecological Oncology (ESGO)/European Society for Radiotherapy & Oncology (ESTRO) classification for endometrial cancer (EC) now includes a high-intermediate risk (HIR) group of recurrence due to the adverse prognostic role of lymphovascular space involvement (LVSI) and grade 3 for women at intermediate risk. However, optimal surgical staging, and especially the place of lymphadenectomy, remains to be elucidated. We aimed to establish whether systematic nodal staging should be part of surgical staging for women with HIR EC. METHODS: We abstracted from a prospectively maintained multicentre database the data of 181 women with HIR EC based on uterine factors (endometrioid type 1, grade 1-2 tumors with deep (≥50%) myometrial invasion and unequivocally positive LVSI, and those with grade 3 tumors with <50% myometrial invasion regardless of LVSI status), who received primary surgical treatment between January 2001 and December 2013. We recorded frequency of lymph node (LN) metastases in those who underwent nodal staging. The secondary outcomes were overall survival and recurrence patterns. RESULTS: Overall, 145 (80.1%) women underwent nodal staging consisting of at least pelvic lymphadenectomy. Of these, 62 (42.7%) had LN disease (9.7% with micrometastases). The respective 5-year overall survival rates according to LN status were 85.0% (95% confidence interval [CI] 76.5-91.4), 71.8% (95% CI 61.9-80.4) and 36.0% (95% CI 26.6-46.2) for women with negative LN, positive LN, and unstaged (p = 0.047). Unstaged women were more likely to experience nodal recurrence than surgically staged/LN negative women (p = 0.05). CONCLUSIONS: Systematic nodal staging should be part of surgical staging for women with apparent ESMO/ESGO/ESTRO HIR EC. Sentinel LN biopsy (SLNB) could be an option in this specific setting that may possibly substitute comprehensive staging, for the identification of patients with lymphatic dissemination.

Improving the clinical management of women with borderline tumours: a recurrence risk scoring system from a French multicentre study.

OBJECTIVE: To develop a risk scoring system (RSS) for predicting recurrence in women with borderline ovarian tumours (BOTs). DESIGN: Cohort study of women with BOTs. SETTING: French multicentre tertiary care centres. POPULATION: A cohort of 360 women with BOTs who received primary surgical treatment between January 2000 and December 2013. METHODS: Clinical and pathological factors affecting recurrence in women with BOTs. MAIN OUTCOME MEASURE: The development of a model for the prediction of recurrence in women with BOTs. RESULTS: Overall the recurrence rate was 20.0% (72/360). Recurrence was associated with five variables: age < 45 years; preoperative serum tumour marker CA125 > 150 IU/mL; a serous histological subtype; International Federation of Gynecology and Obstetrics (FIGO) stage other than IA; and ovarian surgery other than bilateral salpingo-oophorectomy (BSO; i.e. cystectomy and unilateral salpingo-oophorectomy). These variables were included in the RSS and assigned scores ranging from 0 to 6. The discrimination of the RSS was 0.82 (95% confidence interval, 95% CI 0.79-0.85). A total score of 8 points corresponded to the optimal threshold of the RSS, with a rate of recurrence of 11.8% (35/297) and 58.7% (37/63) for women at low risk (<8 points) and women at high risk (≥8 points), respectively. The diagnostic accuracy was 85.0%. CONCLUSIONS: This study shows that the risk of BOT recurrence can be accurately predicted so that women at high risk can benefit from adapted surgical treatment. TWEETABLE ABSTRACT: Our RSS permitted women with BOTs at low risk to be distinguished from women with BOTs at high risk of recurrence.

Axillary lymph node micrometastases decrease triple-negative early breast cancer survival.

BACKGROUND: Triple-negative breast cancers (TNBCs) are the most deadly form of breast cancer (BC) subtypes. Axillary lymph node involvement (ALNI) has been described to be prognostic in BC taken as a whole, but its prognostic value in each subtype is unclear. We explored the prognostic impact of ALNI and especially of small size axillary metastases in early TNBCs. METHODS: We analysed in this multicentre study all patients treated for early TNBC in 12 French cancer centres. We explored the correlation between clinicopathological data and ALNI, with a specific focus on the dichotomisation between macrometastases and occult metastases, which is defined as the presence of isolated tumour cells or micrometastases. The prognostic value of ALNI both in terms of disease-free survival (DFS) and overall survival (OS) was also explored. RESULTS: We included 1237 TNBC patients. Five-year DFS and OS were 83.7% and 88.5%, respectively. The identified independent prognostic features for DFS were tumour size >20 mm (hazard ratio (HR)=1.86; 95% CI: 1.11-3.10, P=0.018), lymphovascular invasion (HR=1.69; 95% CI: 1.21-2.34, P=0.002) and ALNI both in case of macrometastases (HR=1.97; 95% CI: 1.38-2.81, P<0.0001) and occult metastases (HR=1.72; 95% CI: 1.1-2.71, P=0.019). DFS and OS were similar between tumours with occult metastases and macrometastases. Tumours presenting at least two pejorative features (out of ALNI, lymphovascular invasion and large tumour size) displayed a significantly poorer DFS in both the training set and validation set, independently of chemotherapy administration. Tumours with no more than one of the above-cited pejorative features had a 5-year OS of ⩾90% vs 70% for other cases (P<0.0001). CONCLUSIONS: Axillary lymph node involvement is a key prognostic feature for early TNBC when isolated tumour cells were identified in lymph nodes. This impact is independent of chemotherapy use.

Surgical Complexity Impact on Survival After Complete Cytoreductive Surgery for Advanced Ovarian Cancer.

INTRODUCTION: The direct relationship between surgical radicality to compensate biologic behavior and improvement of patient outcome at the time of primary or interval cytoreduction remains unclear. OBJECTIVE: The aim of this study was to evaluate the impact of disease extension and surgical complexity on survival after complete macroscopic resection for stage IIIC-IV ovarian cancer. MATERIALS AND METHODS: Medical records from seven referral centers in France were reviewed to identify all patients who had complete cytoreductive surgery for stage IIIC-IV epithelial ovarian, fallopian, or primary peritoneal cancer. All patients had at least six cycles of carboplatin and paclitaxel combination therapy. RESULTS: From the 374 consecutive patients with complete cytoreduction who were included in this study, stage, grade, upper abdominal disease, surgical complexity, and carcinomatosis extent were significantly associated with disease-free survival (DFS) at univariate analysis. Stage IV and the need for ultra-radical procedures were significantly associated with lower overall survival (OS). On multivariate analysis, radical surgery, including more than two visceral resections, was significantly associated with decreased DFS and OS. CONCLUSIONS: Patients who need complex surgical procedures involving two or more visceral resections in order to achieve successful complete cytoreduction have worse outcome than patients with less extensive procedures. The negative impact of surgical complexity was not significant in patients who underwent upfront procedures. Tumor volume and extension were associated with decreased DFS in patients undergoing a primary surgical approach. This adds to the evidence that, even though complete cytoreduction is currently the objective of surgery, tumor load remains an independent poor prognostic factor and probably reflects a more aggressive behavior.

Nomogram to predict live birth rate after fertility-sparing surgery for borderline ovarian tumours.

STUDY QUESTION: Can a nomogram be used to predict the individual probability of live birth (LB) in women with borderline ovarian tumours (BOTs) receiving primary fertility-sparing surgery? SUMMARY ANSWER: A nomogram built according to the woman's age, histological subtype (serous versus mucinous), type of ovarian surgical treatment and FIGO stage can accurately predict the probability of LB in women with BOT. WHAT IS KNOWN ALREADY: Current prediction models determine the probability of pregnancy after medically assisted reproduction (MAR) and form the basis of patient counselling to guide the decision as to whether to consider in vitro fertilization but do not take into account prediction of the LB rate. STUDY DESIGN, SIZE, DURATION: This was a retrospective multi-centre study including 187 women with fertility-sparing surgery for BOT diagnosed between January 1980 and December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: A multivariate logistic regression analysis of selected factors and a nomogram to predict the subsequent LB rate was constructed. A bootstrapping technique was used for internal validation. MAIN RESULTS AND THE ROLE OF CHANCE: Fifty-one women had LB (27.3%). Taking into account multiple pregnancies, the overall LB rate was 40.1% (75/187). Federation International of Gynaecology and Obstetric (FIGO) stage, age at diagnosis, histological subtype and surgery type were included in the nomogram. The predictive model had an AUC of 0.742 (95% CI, 0.644-0.825) and 0.72 (95% CI, 0.621-0.805) before and after the 200 repetitions of bootstrap sample corrections, respectively, and showed a good calibration. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study cannot exclude all biases. Our nomogram is based on simple criteria, but did not take into account the evaluation of ovarian reserve. It demonstrates a fair relevance, but requires external validation before routine use. WIDER IMPLICATIONS OF THE FINDINGS: Clinicians are increasingly interested in such tools to support the patient in making an informed decision about treatment options. This nomogram contributes to the decision-making by defining simple risk factors of poor LB probability that can help identify good candidates for MAR. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Just how accurate are the major risk stratification systems for early-stage endometrial cancer?

BACKGROUND: To compare the accuracy of five major risk stratification systems (RSS) in classifying the risk of recurrence and nodal metastases in early-stage endometrial cancer (EC). METHODS: Data of 553 patients with early-stage EC were abstracted from a prospective multicentre database between January 2001 and December 2012. The following RSS were identified in a PubMed literature search and included the Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC-1), the Gynecologic Oncology Group (GOG)-99, the Survival effect of para-aortic lymphadenectomy (SEPAL), the ESMO and the ESMO-modified classifications. The accuracy of each RSS was evaluated in terms of recurrence-free survival (RFS) and nodal metastases according to discrimination. RESULTS: Overall, the ESMO -modified RSS provided the highest discrimination for both RFS and for nodal metastases with a concordance index (C-index) of 0.73 (95% CI, 0.70-0.76) and an area under the curve (AUC) of 0.80 (0.78-0.72), respectively. The other RSS performed as follows: the PORTEC1, GOG-99, SEPAL, ESMO classifications gave a C-index of 0.68 (0.66-0.70), 0.65 (0.63-0.67), 0.66 (0.63-0.69), 0.71 (0.68-0.74), respectively, for RFS and an AUC of 0.69 (0.66-0.72), 0.69 (0.67-0.71), 0.68 (0.66-0.70), 0.70 (0.68-0.72), respectively, for node metastases. CONCLUSIONS: None of the five major RSS showed high accuracy in stratifying the risk of recurrence or nodal metastases in patients with early-stage EC, although the ESMO-modified classification emerged as having the highest power of discrimination for both parameters. Therefore, there is a need to revisit existing RSS using additional tools such as biological markers to better stratify risk for these patients.

Contribution of Lymphoscintigraphy for Sentinel Lymph Node Biopsy in Women with Early Stage Endometrial Cancer: Results of the SENTI-ENDO Study.

BACKGROUND: This study was designed to evaluate detection rate and anatomical location of sentinel lymph node (SLN) at lymphoscintigraphy, to compare short and long lymphoscintigraphy protocols, and to correlate lymphoscintigraphic and surgical mapping of SLN in patients with early-stage endometrial cancer (EC). METHODS: Subanalysis of the prospective multicenter study Senti-endo performed from July 2007 to August 2009. Patients with stage I and II EC received four cervical injections of 0-2 mL of unfiltered technetium sulphur colloid the day before (long protocol) or the morning (short protocol) before surgery. SLN detection used a combined technetium/patent blue labeling technique, and all patients had a systematic bilateral pelvic lymphadenectomy. RESULTS: A total of 133 patients were enrolled in the study and 118 (94.5 %) underwent a lymphoscintigraphy. Of these 118 patients, 44 (37 %) underwent a short protocol and 66 (56 %) a long protocol (data on lymphoscintigraphy were not available in eight patients). Lymphoscintigraphic detection rate was 74.6 % (34 % for short protocol and 60.2 % for long protocol). No difference in the detection rate was observed according to lymphoscintigraphy protocol (p = 0.22), but a higher number of SLN was noted for the long protocol (p = 0.02). Aberrant drainage was noted on lymphoscintigraphy in 30.5 % of the patients. Paraaortic SLNs were exclusively detected using the long protocol. A poor correlation was noted between short (κ test = 0.24) or long lymphoscintigraphy (κ test = 0.3) protocol and SLN surgical mapping. CONCLUSIONS: Our study demonstrates that preoperative lymphoscintigraphy allowed a high SLN detection rate and that long lymphoscintigraphy protocol was associated with a higher detection of aberrant drainage especially in the paraaortic area.

Diminished ovarian reserve, premature ovarian failure, poor ovarian responder--a plea for universal definitions.

PURPOSE: Diminished ovarian reserve (DOR) is characterized by poor fertility outcomes, and it represents a major challenge in reproductive medicine. Although consensus exists on the concept of DOR, its definition remains blurry. DOR has to be distinguished from premature ovarian failure (POF) and poor ovarian responders (POR), who are clearly defined. METHODS: We performed a PubMed search with the terms "diminished ovarian reserve" and "in vitro fertilization (IVF)" to assess the homogeneity of the definition of DOR. RESULTS: Out of 121 articles, 14 gave a definition for DOR. Only one definition was used by two different teams (basal follicle-stimulating hormone (FSH) value >10 IU/l) and eight teams used 11 different definitions. Among those, four definitions did not include antral follicular count (AFC) and seven studies did. Two definitions included the results from a previous cycle. CONCLUSIONS: The heterogeneity in the definition of DOR used in these studies contributes to confusing results. Hence, there is a need for a clear definition of DOR. It appears that AFC and anti-Müllerian hormone (AMH) serum levels are the most relevant criteria. One option could be the use of the following definition: (i) woman with any of the risk factors for POR and/or (ii) an abnormal ovarian reserve test (i.e., antral follicular count (AFC) <5-7 follicles or AMH <0.5-1.1 ng/ml). This hypothesis requires validation.

Effect of induced peritoneal endometriosis on oocyte and embryo quality in a mouse model.

PURPOSE: To assess the impact of peritoneal endometriosis on oocyte and embryo quality in a mouse model. METHODS: Peritoneal endometriosis was surgically induced in 33 B6CBA/F1 female mice (endometriosis group, N = 17) and sham-operated were used as control (sham group, N = 16). Mice were superovulated 4 weeks after surgery and mated or not, to collect E0.5-embryos or MII-oocytes. Evaluation of oocyte and zygote quality was done by immunofluorescence under spinning disk confocal microscopy. RESULTS: Endometriosis-like lesions were observed in all mice of endometriosis group. In both groups, a similar mean number of MII oocytes per mouse was observed in non-mated mice (30.2 vs 32.6), with a lower proportion of normal oocytes in the endometriosis group (61 vs 83 %, p < 0.0001). Abnormalities were incomplete extrusion or division of the first polar body and spindle abnormalities. The mean number of zygotes per mouse was lower in the endometriosis group (21 vs 35.5, p = 0.02) without difference in embryo quality. CONCLUSIONS: Our results support that induced peritoneal endometriosis in a mouse model is associated with a decrease in oocyte quality and embryo number. This experimental model allows further studies to understand mechanisms of endometriosis-associated infertility.

A clue towards improving the European Society of Medical Oncology risk group classification in apparent early stage endometrial cancer? Impact of lymphovascular space invasion.

BACKGROUND: Lymphovascular space invasion (LVSI) is one of the most important predictors of nodal involvement and recurrence in early stage endometrial cancer (EC). Despite its demonstrated prognostic value, LVSI has not been incorporated into the European Society of Medical Oncology (ESMO) classification. The aim of this prospective multicentre database study is to investigate whether it may improve the accuracy of the ESMO classification in predicting the recurrence risk. METHODS: Data of 496 patients with apparent early-stage EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from prospective multicentre database. A modified ESMO classification including six risk groups was created after inclusion of the LVSI status in the ESMO classification. The primary end point was the recurrence accuracy comparison between the ESMO and the modified ESMO classifications with respect to the area under the receiver operating characteristic curve (AUC). RESULTS: The recurrence rate in the whole population was 16.1%. The median follow-up and recurrence time were 31 (range: 1-152) and 27 (range: 1-134) months, respectively. Considering the ESMO modified classification, the recurrence rates were 8.2% (8 out of 98), 23.1% (15 out of 65), 25.9% (15 out of 58), and 45.1% (28 out of 62) for intermediate risk/LVSI-, intermediate risk/LVSI+, high risk/LVSI-, and high risk/LVSI+, respectively (P<0.001). In the low risk group, LVSI status was not discriminant as only 7.0% (14 out of 213) had LVSI+. The staging accuracy according to AUC criteria for ESMO and ESMO modified classifications were of 0.71 (95% CI: 0.68-0.74) and 0.74 (95% CI: 0.71-0.77), respectively. CONCLUSIONS: The current modified classification could be helpful to better define indications for nodal staging and adjuvant therapy, especially for patients with intermediate risk EC.

Prognostic factors for recurrence after conservative treatment in a series of 119 patients with stage I serous borderline tumors of the ovary.

BACKGROUND: The aim of this study was to evaluate prognostic factors for recurrence after conservative treatment of a large series of 'apparent' stage I serous borderline ovarian tumors (SBOTs). PATIENTS AND METHODS: A review of 119 patients treated conservatively between 2000 and 2009 with follow-up data. All pathological slides were reviewed by the same expert pathologist. Prognostic factors for recurrence were studied (age, histological subtypes and surgical procedure). RESULTS: Conservative surgical procedures were: unilateral cystectomy (n = 43, 36%); unilateral adnexectomy (UA; n = 50, 42%); bilateral cystectomies (n = 11, 9%) and UA + contralateral cystectomy (n = 15, 13%). Stromal microinvasion and/or a micropapillary pattern was present in 21 (18%) and 13 (11%) patients, respectively. With a median follow-up of 45 months, 38 (32%) patients relapsed (10 also had peritoneal disease in the form of noninvasive implants at the first recurrence). In 2 of these 38 patients, progression-to-invasive disease occurred at the second and third relapse (one patient died to the recurrence). Three prognostic factors for recurrence were identified in the univariate analysis: a young age (< or >30 years old), the type of conservative treatment (adnexectomy versus cystectomy) and tumor bilaterality. In the multivariate analysis, only age remained statistically significant. CONCLUSION: In this series (the largest reported, to date, on recurrences after the conservative management of stage I SBOT), the risk of relapse was not related to tumor histological subtypes (micropapillary and stromal microinvasion) nor to the use of complete staging surgery. Invasive recurrences were very rare in stage I SBOT, but did occur. A young age, tumor bilaterality and the use of a cystectomy were identified as risk factors for recurrence, suggesting that management of fertility preservation (particularly in very young patients) should be associated with a meticulously conducted follow-up.

Influence of histological subtypes on the risk of an invasive recurrence in a large series of stage I borderline ovarian tumor including 191 conservative treatments.

BACKGROUND: The overall prognosis of stage I borderline ovarian tumors (BOT) is excellent but a small percentage of patients die to their disease. The prognostic factors for such a rare event are still not clearly defined. The aim of this study was to determine these factors for recurrence per se and recurrence in the form of invasive carcinoma in a large series of stage I tumors. METHODS: A retrospective review of patients with BOT. Three inclusion criteria were defined: (i) a centralized histological review; (ii) macroscopic stage I tumors; (iii) exclusion of metastatic disease to the ovaries. RESULTS: From 2000 to 2010, 254 patients fulfilled inclusion criteria [140 had mucinous BOT (MBOT) and 114 a serous BOT (SBOT)], and 191 had undergone conservative management. After a median follow-up of 45 months, 43 patients had developed recurrences (31 borderline and 12 invasive). The risks of recurrences were statistically increased after conservative treatment, particularly after a cystectomy, in patients with stage IB and among patients with incompletely staged tumors. In the subgroup of conservatively treated patients (representing 75% of our population), the risks of recurrences were statistically increased in patients affected by a SBOT, in patients who had undergone a cystectomy, in patients with stage IB disease and in patients with a micropapillary pattern (MPP). MBOT and the presence of a MPP were identified as prognostic factors for invasive disease. CONCLUSIONS: In the present series of BOT with the largest number of patients treated conservatively to date, the presence of a MPP and the mucinous subtype were associated with a higher rate of progression to carcinoma after conservative management. These important results suggest that MBOT belong to a 'high-risk' group likely to develop an invasive recurrence after fertility-sparing surgery in stage I BOT.

External multicentre validation of a nomogram predicting the risk of relapse in patients with borderline ovarian tumours.

BACKGROUND: The Obermair nomogram was recently developed to predict the risk of relapse in patients with borderline ovarian tumours (BOTs) based on five readily available clinical, biological, and pathological characteristics. We set out to externally validate and assess its robustness using a multi-institutional BOT database. METHODS: All consecutive patients treated for BOTs in the two participating centres between January 1980 and December 2008 and who had all the nomogram variables documented were identified for analysis. RESULTS: Three hundred and fourteen eligible patients were identified and used for external validation analysis. The median follow-up and initial relapse time were 46.43 (range: 0.1-360) and 66.64 (range: 8-77) months, respectively. The nomogram concordance index was 0.54 (95% CI, 0.52-0.56). The correspondence between the actual relapse and the nomogram predictions suggests a limited calibration of the nomogram in the validation cohort. CONCLUSION: This external validation study of the Obermair nomogram showed limitations in its generalisability to a new and independent patient population.