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BackgroundPositron emission tomography/computed tomography (PET/CT) fails to detect approximately 25% of aortic lymph node metastasis in patients with PET/CT stage IIIC1 cervical cancer. Surgical staging could lead to treatment modification and to improved para-aortic and distant control.Primary Objective(s)To demonstrate if chemoradiation with tailored external beam radiation field based on surgical staging and pathologic examination of the para-aortic lymph node is associated with improved 3-year disease-free survival compared with patients staged with PET/CT staging only.Study HypothesisSurgical staging followed by tailored chemoradiation will improve disease-free survival while avoiding unnecessary prophylactic extended-field chemoradiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 cervical cancer.Trial DesignThis is an international multicenter, randomized, phase III study. Eligible patients will be randomized 1:1 between PET/CT staging followed by chemoradiation (control arm), or surgical staging followed by tailored chemo-radiation (experimental arm). Randomization will be stratified by tumor stage according to TNM classification, center, and adjuvant treatment.Major Inclusion/Exclusion CriteriaMain inclusion criteria are histologically proven PET/CT FIGO stage IIIC1 cervical cancer. Main exclusion criteria include unequivocal positive common iliac or para-aortic lymph node at pre-therapeutic imaging PET/CT.Primary Endpoint(s)The primary endpoint is disease-free survival defined as the time from randomization until first relapse (local, regional, or distant), or death from any cause.Sample Size510 eligible patientsEstimated Dates for Completing Accrual and Presenting ResultsThe estimated date for completing accrual will be Q2 2027. The estimated date for presenting results will be Q4 2030.Trial Registration NumberNCT05581121.

Objective Based on the SUCCOR study database, our primary objective was to identify the independent clinical pathological variables associated with the risk of relapse in patients with stage IB1 cervical cancer who underwent a radical hysterectomy. Our secondary goal was to design and validate a risk predictive index (RPI) for classifying patients depending on the risk of recurrence. Methods Overall, 1116 women were included from January 2013 to December 2014. We randomly divided our sample into two cohorts: discovery and validation cohorts. The test group was used to identify the independent variables associated with relapse, and with these variables, we designed our RPI. The index was applied to calculate a relapse risk score for each participant in the validation group. Results A previous cone biopsy was the most significant independent variable that lowered the rate of relapse (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.17–0.60). Additionally, patients with a tumor diameter >2 cm on preoperative imaging assessment (OR 2.15, 95% CI 1.33–3.5) and operated by the minimally invasive approach (OR 1.61, 95% CI 1.00–2.57) were more likely to have a recurrence. Based on these findings, patients in the validation cohort were classified according to the RPI of low, medium, or high risk of relapse, with rates of 3.4%, 9.8%, and 21.3% observed in each group, respectively. With a median follow-up of 58 months, the 5-year disease-free survival rates were 97.2% for the low-risk group, 88.0% for the medium-risk group, and 80.5% for the high-risk group (p < 0.001). Conclusion Previous conization to radical hysterectomy was the most powerful protective variable of relapse. Our risk predictor index was validated to identify patients at risk of recurrence.

Assess efficacy, safety, fertility outcomes and recurrence after laparoscopic resection of bladder endometriosis (BE) using a CORetrospective cohort study.University gynecologic surgery unit, referral center for endometriosis.A total of 207 women having undergone laparoscopic BE excision between January 1998 and January 2019.None.Intra- and postoperative complication rates. Disease recurrence and fertility outcomes in patients with a minimum 1-year follow-up (n = 176) for "isolated" and "non-isolated" BE groups.Forty-three patients presented with isolated BE. Bladder "shaving" without mucosae opening was performed in 50.7% cases. No intraoperative complications were noted. One postoperative grade 3 complication was related to BE excision: a bladder breach requiring closure by repeat laparoscopy. Mean (± SD) follow-up was 7.05 (± 4.65) years. In patients wishing to conceive (n = 132), the total pregnancy rate (PR) was 75% (48.5% spontaneous), 76.19% in the isolated BE group (56.3% spontaneous). Among the 94 patients with previous infertility, 74.5% conceived, 50% spontaneously. No statistical difference was found in PR and need for in vitro fertilization between isolated and nonisolated BE groups. BE recurrence rate was 3.4%. No difference was observed between groups with full-thickness bladder resection (4/88) and shaving (2/88) (p = .406). Age at surgery (hazard ratio 0.91 [0.84-0.98], p = .016) and postoperative pregnancy (hazard ratio 0.07 [0.01-0.91], p = .042) showed influence on disease recurrence.The study demonstrates that laparoscopic BE removal is feasible with very low complications rates and was associated with high PR (both spontaneous and in vitro fertilization), even in patients with previous infertility. BE recurrence is lower than for other endometriosis locations. Bladder endometriosis; Laparoscopy; Deep infiltrating endometriosis; Fertility; Partial bladder resection.

Objective Extended field chemoradiation is recommended for patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) metastases. The radiation planning may be based on PET/CT while others recommend to rely on surgical staging. We report the rate of patients for whom the radiation field defined on PET/CT was modified by the histological PALN status. Methods Between March 2010 and December 2016, 168 consecutive patients with LACC underwent a pre-therapeutic PET/CT and PALN dissection. The data were reviewed retrospectively. The diagnostic performance of the PET/CT for definition of PALN status was calculated. We determined the percentage of patients for whom PALN dissection altered the external beam radiotherapy (EBRT) field defined on the PET/CT basis. Results Of 151 patients with negative PALNs on PET/CT, 26 had histological PALN metastases. Of 17 patients with positive PALNs on PET/CT, 9 were negative on histology of which 7 were located in the common iliac region. Sensitivity, specificity, positive and negative predictive value of PET/CT were 23.5, 93.3, 47.1 and 82.8% respectively. In total, 35 out of 168 patients underwent EBRT - field adaptation (pelvic vs extended field). The rate of radiation field modification (27,7%) was particularly high in the subgroup of patients with metastatic pelvic lymph nodes (PLNs) on PET/CT. Conclusion Para-aortic surgical staging contributes significantly to individualize the radiation treatment of patients with LACC, particularly for those with positive PLNs at PET/CT. Indication of surgical staging deserves particular attention when the PET/CT suggests positive LNs in the common iliac region.

The long delay between asbestos exposure and the development of mesothelioma will likely result in an increased incidence of mesothelioma in our industrialized societies. Radiation therapy is another factor known to induce these tumors. We describe a rare case of foamy looking mesothelioma in a 63-year-old patient with a long oncology history of a supposed peritoneal carcinomatosis. The pathologist was faced with a diagnostic pitfall as this peritoneal clear cell tumor expressed transcription factor binding to immunoglobulin heavy constant mu enhancer 3 (TFE3) at the nuclear level. Fortunately, the pathologist performed an extensive panel of immunomarkers, leading to a final diagnosis of epithelioid mesothelioma. Thus, we describe the first case of mesothelioma expressing TFE3. Note that there was no rearrangement of TFE3 in fluorescence in situ hybridization.

OBJECTIVE: Voiding dysfunctions represent a leading morbidity after radical hysterectomy performed in patients with early-stage cervical cancer. The aim of this study was to perform ad hoc analysis of factors influencing voiding recovery in SENTIX (SENTinel lymph node biopsy in cervIX cancer) trial. METHODS: The SENTIX trial (47 sites, 18 countries) is a prospective study on sentinel lymph node biopsy without pelvic lymphadenectomy in patients with early-stage cervical cancer. Overall, the data of 300 patients were analysed. Voiding recovery was defined as the number of days from surgery to bladder catheter/epicystostomy removal or to post-voiding urine residuum ≤50 mL. RESULTS: The median voiding recovery time was three days (5th-95th percentile: 0-21): 235 (78.3%) patients recovered in 30 days. In the multivariate analysis, only previous pregnancy (p = 0.033) and type of parametrectomy (p < 0.001) significantly influenced voiding recovery >7 days post-surgery. Type-B parametrectomy was associated with a higher risk of delayed voiding recovery than type-C1 (OR = 4.69; p = 0.023 vs. OR = 3.62; p = 0.052, respectively), followed by type-C2 (OR = 5.84; p = 0.011). Both previous pregnancy and type C2 parametrectomy independently prolonged time to voiding recovery by two days. CONCLUSIONS: Time to voiding recovery is significantly related to previous pregnancy and type of parametrectomy but it is not influenced by surgical approach (open vs minimally invasive), age, or BMI. Type B parametrectomy, without direct visualisation of nerves, was associated with longer recovery than nerve-sparing type C1. Importantly, voiding dysfunctions after radical surgery are temporary, and the majority of the patients recover in less than 30 days, including patients after C2 parametrectomy.

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review. ispartof: CANCERS vol:12 issue:5 ispartof: location:Switzerland status: published

RESEARCH QUESTION: Does ulipristal acetate (UPA) modify the expression of genes related to apoptosis or the extracellular matrix in uterine myomas and are any modifications associated with a clinical response? DESIGN: Targeted analysis of 176 apoptosis- or extracellular-matrix-related genes was conducted using polymerase chain reaction (PCR) arrays. Relevant results were validated by quantitative PCR. Four groups were established: responsive short-term (one course, n = 9), responsive long-term (two to four courses, n = 9), non-responsive (n = 9), and the control group who was not given any hormone therapy (n = 9). The clinical response was monitored by medical imagery and considered significant when volume reduction was greater than 25%. RESULTS: Compared with untreated myomas, significant changes in expression of four genes were found in UPA-treated myomas. Gene expression of integrin subunit beta 4 was repressed by UPA treatment (fold change [FC] = -12.50, P < 0.001, q < 0.001), tenascin-C expression was downregulated in UPA-responsive patients (FC = -2.50, P = 0.010, q = 0.090), survivin was repressed in short-term UPA-responsive tumours (FC = -7.69, P < 0.001, q = 0.010), and catenin delta 2 gene expression was upregulated in non-responsive myomas (FC = +7.36, P < 0.001, q = 0.010). CONCLUSION: This characterization provides the first molecular distinction between myomas responsive or non-responsive to UPA treatment.

Study question How effective is ovarian tissue cryopreservation (OTC)? Summary answer In our cohort of patients who underwent OTC, premature ovarian failure (POF) rates, return rates and pregnancy rates after autotransplantation were 31.5, 4.4 and 33%, respectively. What is known already OTC for fertility purposes has been performed for >20 years now. With over 86 live births reported worldwide and success rates of ~30% after autotransplantation of frozen-thawed ovarian cortex, the procedure should no longer be considered experimental. However, very few publications report the efficacy of this procedure. Study design, size, duration Cases of ovarian tissue cryobanking for fertility preservation performed between 1997 and 2013 in a single institution were reviewed by analysis of the cryobank database and a prospective questionnaire sent out in March 2015. Participants/materials, setting, methods There were 545 patients who underwent OTC during this period. The analysis included indications for OTC, survival rates, ovarian function and spontaneous pregnancies after OTC, come-back rates for ovarian tissue transplantation, pregnancy rates after transplantation, and complication and satisfaction rates. Main results and the role of chance OTC was performed in this cohort at a mean age of 22.3 ± 8.8 years for oncological indications (79%), benign gynecological pathologies (17.5%) and genetic risks of POF (3.5%). Of the 545 patients, 29% were under 18 years of age at the time of OTC and 15% were prepubertal. While 10% of patients died from their disease, 21 patients (3.9%) underwent autotransplantation, 7 of whom delivered a healthy baby, yielding a post-transplantation live birth rate of 33%. Of 451 patients who were sent the questionnaire, 143 agreed to respond (32%). Nevertheless, ovarian function could not be evaluated in 36% of those who answered. Of 92 evaluable patients, 31.5% were menopausal and 68.5% showed persistent ovarian function. Of 52 women who attempted to conceive naturally, 37 were successful (71%). Among 140 patients who answered the questionnaire, 96% were satisfied with the procedure and only 1 major complication (intra-abdominal hemorrhage) was encountered. Among all the patients, 12% have donated their ovarian cortex for research purposes or have had it destroyed. Limitations, reasons for caution The questionnaire participation rate (32%), limited follow-up (mean 7.6 ± 3.5 years) and use of only clinical criteria for evaluation of ovarian function made it difficult to accurately assess the risk of POF and efficiency of OTC. Wider implications of the findings Our findings confirm a 30% pregnancy rate after ovarian cortex autotransplantation but also stress the difficulties of evaluating the real efficacy of OTC. Study funding/competing interest(s) No funding was sought for this study and none of the authors have any conflict of interest. Trial registration number ClinicalTrials.gov Registration ID: CRYOFONOV01.

SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer FREE http://orcid.org/0000-0002-1908-3251Luis Chiva1, Vanna Zanagnolo2, Denis Querleu3, Nerea Martin- Calvo4, Juan Arévalo-Serrano5, Mihai Emil Căpîlna6, Anna Fagotti7, Ali Kucukmetin8, Constantijne Mom9, Galina Chakalova10, Shamistan Aliyev11, Mario Malzoni12, http://orcid.org/0000- 0001-5809-3535Fabrice Narducci13, Octavio Arencibia14, Francesco Raspagliesi15, Tayfun Toptas16, David Cibula17, Dilyara Kaidarova18, http://orcid.org/0000-0001-6763-9720Mehmet Mutlu Meydanli19, Mariana Tavares20, Dmytro Golub21, http://orcid.org/0000-0003-3140-4772Anna Myriam Perrone22, Robert Poka23, Dimitrios Tsolakidis24, Goran Vujić25, http://orcid.org/0000-0001-8935- 0311Marcin A Jedryka26, Petra L M Zusterzeel27, Jogchum Jan Beltman28, Frederic Goffin29, Dimitrios Haidopoulos30, Herman Haller31, Robert Jach32, Iryna Yezhova33, Igor Berlev34, Margarida Bernardino35, Rasiah Bharathan36, Maximilian Lanner37, Minna M Maenpaa38, http://orcid.org/0000-0002-4403-3707Vladyslav Sukhin39, Jean-Guillaume Feron40, Robert Fruscio41, 42, Kersti Kukk43, Jordi Ponce44, Jose Angel Minguez45, http://orcid.org/0000-0002-9618- 5606Daniel Vázquez-Vicente45, Teresa Castellanos45, Enrique Chacon46 and http://orcid.org/0000-0002-9700-0853Juan Luis Alcazar47 On behalf of the SUCCOR study Group Author affiliations Abstract Background Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. Methods We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. Results Mean age was 48.3 years (range ; 23–83) while the mean BMI was 25.7 kg/m2 (range ; 15–49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07 ; 95% CI, 1.35 to 3.15 ; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45 ; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76 ; 95% CI, 1.75 to 4.33 ; P

Introduction/Background Despite the use of nerve-sparing technique, bladder dysfunction remains the leading morbidity associated with parametrectomy (radical hysterectomy or trachelectomy). Our aim was to analyze the time to postoperative voiding recovery and the factors influencing it in the SENTIX trial cohort, in whom different types of surgical approach and parametrectomy was used. Methodology The SENTIX trial is a prospective cohort international study on sentinel lymph node biopsy without pelvic lymphadenectomy in patients with early-stage cervical cancer (≤4 cm or ≤2cm in fertility sparing). It entails 46 sites from 18 countries. Ad hoc analysis of data from the SENTIX trial was performed to assess factors influencing voiding recovery, which was defined as the number of days from surgery to bladder catheter or epicystostomy removal with post-voiding urine residuum Result The characteristics of the cohort of 372 patients are shown in table 1. Median (range) voiding recovery time was 3 (0–21) days; it was 1 month, only 1 case (80 days) was not associated with any severe intraoperative complication (6 cases) or adjuvant radiotherapy (3 cases). Tumor size >2 cm, open surgery, and a more extensive type of parametrectomy significantly influenced voiding recovery (figure 1). In multivariate analysis, only previous pregnancy and type of parametrectomy were significant (table 2). Conclusion Voiding recovery time is directly related to the extent of parametrectomy. It is, however, temporary and almost all patients recover within 1 month, even after a more radical procedure (C2). The higher risk associated with laparotomy reflects a tendency to be more radical with open surgery. Disclosure This work was supported by a grant from the Czech Research Council (No 16-31643A). There are no conflicts of interest.

Introduction/Background Extended field chemoradiation is recommended for patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) metastases. The radiation planning may be based on the positron emission tomography-computed tomography (PET/CT) while others recommend to rely on a surgical staging. We report the rate of patients for whom the radiation field defined on a PET/CT basis was modified by the histological PALN status. Methodology Between March 2010 and December 2016, 168 consecutive patients with LACC underwent a pre-therapeutic PET/CT and PALN dissection. The data were reviewed retrospectively. The diagnostic performance of the PET/CT for definition of PALN status was calculated. We determined the percentage of patients for whom PALN dissection altered the external beam radiation treatment (EBRT) field defined on the PET/CT basis. Results Of the 151 patients with negative PALNs on PET/CT, 26 had histological PALN metastasis. Of the 17 patients with positive PALNs on PET/CT, 9 were negative on histology. Seven of these 9 false positive cases were located in the common iliac region. Sensitivity, specificity, positive and negative predictive value of PET/CT were 23.5, 93.3, 47.1 and 82.8% respectively. In total, 35 out of 168 patients underwent EBRT-field adaptation (pelvic vs extended field). The rate of radiation field modification was particularly high (27,7%) in the subgroup of patients with metastatic pelvic lymph nodes (PLNs) on PET/CT. Conclusion Para-aortic surgical staging contributes significantly to individualize the radiation treatment of patients with LACC, particularly for those with positive PLN at PET/CT. Indication of surgical staging deserves particular attention when the PET/CT suggests positive lymph nodes in the common iliac region. Disclosure Nothing to disclose.

Introduction/Background Several studies suggest that oncological surgery induce an acute inflammatory response, and that it may exacerbate certain mechanisms related to tumor growth and eventual dissemination. We propose to investigates whether the administration of Ketorolac (Taradyl)®, a nonsteroidal anti-inflammatory drug, given intraoperatively during surgery for ovarian, tubal, or peritoneal cancer, influences disease free survival (DFS) and Overall survival (OS). Methodology A Retrospective analysis of all the patients operated at Cliniques Universitaires Saint-Luc; Brussel between 2015 and 2017 for ovarian, fallopian tube or peritoneum cancer. All the patient were included from the UCLouvain Network of Gynaecological Oncology (UNGO), an academic network in Belgium for centralisation of the surgery for ovarian cancer patient. Results Of the 90 patients who met the inclusion criteria, 68% received Ketorolac intraoperatively. Only age was statistically different between the two groups (p Conclusion These results suggest that the intraoperative administration of Ketorolac during surgery for ovarian, tubal or peritoneal cancer has a positive effect on the risk of recurrence and median survival. Disclosure Nothing to disclose.

Extended field chemoradiation is recommended for patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) metastases. The radiation planning may be based on PET/CT while others recommend to rely on surgical staging. We report the rate of patients for whom the radiation field defined on PET/CT was modified by the histological PALN status.Between March 2010 and December 2016, 168 consecutive patients with LACC underwent a pre-therapeutic PET/CT and PALN dissection. The data were reviewed retrospectively. The diagnostic performance of the PET/CT for definition of PALN status was calculated. We determined the percentage of patients for whom PALN dissection altered the external beam radiotherapy (EBRT) field defined on the PET/CT basis.Of 151 patients with negative PALNs on PET/CT, 26 had histological PALN metastases. Of 17 patients with positive PALNs on PET/CT, 9 were negative on histology of which 7 were located in the common iliac region. Sensitivity, specificity, positive and negative predictive value of PET/CT were 23.5, 93.3, 47.1 and 82.8% respectively. In total, 35 out of 168 patients underwent EBRT - field adaptation (pelvic vs extended field). The rate of radiation field modification (27,7%) was particularly high in the subgroup of patients with metastatic pelvic lymph nodes (PLNs) on PET/CT.Para-aortic surgical staging contributes significantly to individualize the radiation treatment of patients with LACC, particularly for those with positive PLNs at PET/CT. Indication of surgical staging deserves particular attention when the PET/CT suggests positive LNs in the common iliac region.

OBJECTIVE: To observe alterations in surgical planning that were due to the use of ulipristal acetate (UPA) 5 mg daily for symptomatic uterine fibroids. METHODS: A prospective cohort trial involving women with symptomatic fibroids was undertaken in 23 clinical practice sites within Belgium between October 1, 2014, and March 31, 2016, to compare initial surgical planning to performed surgical procedures following the use of UPA 5 mg daily for 3 months. Secondary outcomes were surgical complications, reduction in fibroids, bleeding control, and adverse effects. RESULTS: Two hundred and twenty-two women were recruited for the trial. The requirement for surgery decreased with the use of UPA, with 54% of women undergoing surgery after treatment. The reduction in surgery performed was lower for women willing to conceive (40%) compared to women who were not (49%). The volume of the fibroids decreased significantly, with the largest measured fibroid decreasing by 50%. Bleeding and pain were significantly decreased with the use of UPA. No major complications were recorded, and no liver function abnormalities were reported during the treatment and in follow-up. CONCLUSION: By administering UPA, the required rate of surgery was significantly decreased. Also, the resulting reduction in size of the fibroids could have the potential benefit of reducing surgery-related complications, and long-term use may be warranted to avoid surgery completely.

Objective. Endometrial carcinoma (EC) is the sixth most common cancer in women and therapies are limited for advanced and recurrent disease. Patient-derived tumor xenograft (PDTX) models are becoming popular tools in translational research because of their histological and genetic similarity to the original tumors and the ability to predict therapeutic response to treatments. Here, we established and characterized a panel of 24 EC PDTX models which includes the major histological and genetic subtypes observed in patients. Methods. Fresh tumor tissues collected from primary, metastatic and recurrent type I and type II EC patients were engrafted in immunocompromised mice. Histology, vimentin, and cytokeratin expression were evaluated, together with Microsatellite instability (MSI), mutation profiling by Whole Exome Sequencing and copy number profiling by Whole Genome Low Coverage Sequencing. The efficacy of both PI3K and MEK inhibitors was evaluated in a model of endometrioid carcinoma harboring PTEN, PIK3CA and KRAS mutations. Results. We observed good similarity between primary tumors and the corresponding xenografts, at histological and genetic level. Among the engrafted endometrioid models, we found a significant enrichment of MSI and POLE mutated tumors, compared to non-engrafted samples. Combination treatment with NVP-EZ235 and AZD6244 showed the possibility to stabilize the tumor growth in one model originated from a patient who already received several lines of chemotherapy. Conclusion. The established EC PDTX models, resembling the original human tumors, promise to be useful for preclinical evaluation of novel combination and targeted therapies in specific EC subgroups. (C) 2015 Elsevier Inc. All rights reserved

Objectives: To evaluate the efficacy and safety of gonadotropin-releasing hormone (GnRH) agonist after endometrial resection in women suffering early stage endometrial carcinoma (EC) and/or endometrial intra-epithelial neoplasia (EIN). Design: A retrospective review of clinical files between January 1999 and December 2016. Setting: University hospital. Patients: Eighteen women younger than 41 years with grade 1 endometrial carcinoma (G1EC) and/or Endometrial intra-epithelial neoplasia (EIN). Interventions: All patients received GnRH agonist for 3 months after an endometrial resection combined with a laparoscopy to exclude concomitant ovarian tumor and/or other extra-uterine disease. The patient underwent a follow-up of 3 months interval with endometrial sampling by hysteroscopy. Main Outcome Measure(s): The recurrence rate and the pregnancy rate after fertility sparing treatment. Results: We identified 9 patients with EIN (50%), 7 patients with G1EC (38.9%), 1 with combined histology (5.5%), and 1 with G2EC (5.5%). After a median follow-up of 40.7 months, 12 patients conserved their uterus (66.7%), and 8 (53.3%) patients were pregnant with a total of 14 pregnancies among those who tried to become pregnant. We observed a complete response rate in 12 patients (66.7%) but 3 of these patients relapsed (25%). We also found a stable disease in 6 patients (33.3%). Conclusions: Compared with other fertility sparing treatments, GnRH agonist after surgery is an effective fertility-sparing strategy for women with EIN and/or G1EC. We recommend hysterectomy once a family has been completed even if the literature does not clearly lead to radical surgery.

We describe here the case of a 23-year old woman with small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT) with SMARC-A4 mutation who benefited from surgery in two steps leading to a total hysterectomy with bilateral salpingo-oophorectomy, omentectomy, pelvic and lombo-aortic lymph nodes dissection. She also received 6 courses of poly-chemotherapy after the surgery. A close follow-up was then performed by clinical examination every three months with determination of serum calcium and CA125 level as well as imaging with thoraco-abdominal CT scan. To date, the patient has a disease-free survival of more than 9 years. We also reviewed the literature on this topic and discuted the new diagnostic and prognostic genetic tool SMARC-A4 mutation.

ContextUlipristal acetate (UPA), a selective progesterone receptor modulator, clinically reduces uterine myoma size in 80% of cases. However, the molecular mechanism of action is still poorly understood, as is the reason why 20% of myomas do not respond to treatment.ObjectiveTo elucidate whether matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are associated with myoma volume shrinkage after UPA therapy.DesignProspective study.SettingAcademic research unit of a university hospital.PatientsUterine biopsies were obtained from 59 patients with symptomatic myomas undergoing myomectomy, 45 of whom were treated preoperatively with either one or greater than or equal to two, 3-month courses of UPA and 14 not given any hormone therapy to serve as controls. Myoma volume was individually monitored during UPA therapy to determine any substantial clinical response (defined as a reduction in volume of >25%). Three groups were established based on the response to treatment: responsive (R) after one course (n = 12); R after two to four courses (n = 15); and nonresponsive (NR; n = 18).InterventionsUPA treatment given as preoperative management for symptomatic myomas.Main Outcome MeasuresMMP and TIMP expression assessed by zymography and immunohistochemistry.ResultsCompared with controls and NR myomas, responders showed significantly higher expression levels for MMP-1 (P < 0.0001) and MMP-2 (P = 0.009) and significantly lower expression levels for TIMP-1 (P = 0.040).ConclusionsThe correlation found between MMP expression and volume fold change supports the notion that MMPs play a key role in UPA-induced myoma shrinkage.

ObjectiveComplete tumor cytoreduction seems to be beneficial for patients with recurrent epithelial ovarian cancer (REOC). The challenge is to identify patients eligible for such surgery. Several scores based on simple clinical parameters have attempted to predict resectability and help in patient selection for surgery in REOC.The aims of this study were to assess the performance of these models in an independent population and to evaluate the impact of complete resection.Materials and MethodsA total of 194 patients with REOC between January 2000 and December 2010 were included in 2 French centers. Two scores were used: the AGO DESKTOP OVAR trial score and a score from Tian et al.The performance (sensitivity, specificity, and predictive values) of these scores was evaluated in our population. Survival curves were constructed to evaluate the survival impact of surgery on recurrence.ResultsPositive predictive values for complete resection were 80.6% and 74.0% for the DESKTOP trial score and the Tian score, respectively. The false-negative rate was high for both models (65.4% and 71.4%, respectively). We found a significantly higher survival in the patients with complete resection (59.4 vs 17.9 months,P< 0.01) even after adjustment for the confounding variables (hazard ratio [HR], 2.53; 95% confidence interval, 1.01–6.3;P= 0.04).ConclusionsIn REOC, surgery seems to have a positive impact on survival, if complete surgery can be achieved. However, factors predicting complete resection are not yet clearly defined. Recurrence-free interval and initial resection seem to be the most relevant factors. Laparoscopic evaluation could help to clarify the indications for surgery.

ObjectivesTo evaluate the outcome of maximal cytoreductive surgery in patients with stage IIIC to stage IV ovarian, tubal, and peritoneal cancer regarding overall survival (OS) and disease-free survival (DFS).Materials and MethodsFive hundred twenty-seven patients with stage IIIC (peritoneal) and stage IV (pleural) ovarian, fallopian tube, and peritoneal carcinoma underwent surgery between January 2003 and December 2007 in 7 gynecologic oncology centers in France. Patients undergoing primary and interval debulking surgery were included, whichever the number of chemotherapy cycles. The extent of disease, type of surgical procedure, and amount of residual disease were recorded. A multivariate analysis of the outcome was performed, taking into account the stage, grade, and timing of surgery.ResultsMedian DFS was 17.9 months, but median OS was not reached at the time of analysis. Complete cytoreductive surgery, without evident residual tumor at the end of the procedure, was obtained in 71% of all patients (primary surgery, 33%). After neoadjuvant therapy, the rate of complete debulking surgery was higher (74%) compared to primary cytoreductive surgery (65%). Twenty-three percent of patients needed “ultra radical surgery” to achieve this goal. The most significant predictive factor for DFS and OS was complete cytoreductive surgery compared to any amount, even minimal (1–10 mm), of residual disease. In the group of patients with complete cytoreductive surgery, the patients undergoing surgery before chemotherapy showed better DFS than those having first chemotherapy.ConclusionThe findings confirm that complete cytoreduction is the criterion standard of surgery in the management of advanced ovarian, peritoneal, and fallopian tube cancer, whatever the timing of surgery. With experienced teams, surgery was completed, without evident residual tumor in 71% of the cases.

The purpose of this study was to analyze complication and recurrence rates after deep endometriotic nodule surgery. A total of 3,298 cases of deep endometriotic nodules were analyzed. The shaving technique was used, avoiding bowel resection. Laparoscopic nodule resection was performed successfully in all cases. Major complications included: (1) rectal perforation in 42 cases (1.3 %), (2) ureteral retention (

Renal clear cell carcinoma (RCC) can lead to metastases in unusual sites, but rarely in the ovary. Differentiation between primary ovarian tumors and ovarian metastases from RCC has different prognostic and therapeutic implications. As ovarian metastasis from RCC resembles a primary ovarian tumor, diagnosis often presents a histopathological challenge. Immunohistochemistry has proved very useful in distinguishing primary ovarian lesions from RCC metastases in the ovary, generally using CK7, CK20, vimentin, ER and CA125. There are 15 documented cases in the English literature of ovarian metastases developing from RCC confirmed by immunohistochemistry, often discovered during follow-up of the primary renal carcinoma. The search engine used for the literature review was PUBMED with “renal clear cell carcinoma”, “ovary”, and “ovarian metastasis” as key words. Here we present the 16th case of RCC metastasis in the ovary, first appearing as highly hemorrhagic tumors.

MR images depict a marked response to Ulipristale Acetate in a woman with large uterine fibroids, and demonstrate no significant regrowth during pregnancy or 12 weeks postpartum

International audience; 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.

OBJECTIVE: To study the pregnancy rate after ulipristal acetate (UPA) therapy for fibroids. DESIGN: Retrospective analysis of a series of 52 patients prospectively included in the PGL4001 (ulipristal acetate) Efficacy Assessment in Reduction of Symptoms Due to Uterine Leiomyomata (PEARL) II and III trials. SETTING: Academic hospital. PATIENT(S): Among the 52 patients, 21 wished to conceive upon treatment completion. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy rate and live birth rate. RESULT(S): Twenty-one patients attempted to get pregnant, among whom 15 (71%) succeeded, totaling 18 pregnancies. Among these 18 pregnancies, 12 resulted in the birth of 13 healthy babies and 6 ended in early miscarriage. No regrowth of fibroids was observed during pregnancy. CONCLUSION(S): We report the first series of pregnancies achieved after UPA treatment. Our data confirm a sustained long-term effect after UPA therapy.

Background: In ovarian cancer, the increased rate of radical surgery comprising upper abdominal procedures has participated to improve overall survival (OS) in advanced stages by increasing the rate of complete cytoreductions. However, in the context of non-resectability, it is unclear whether radical surgery should be considered when it would lead to microscopic but visible disease (≤1 cm). We aimed to compare the survival outcomes among patients with incomplete cytoreduction according to the extent of surgery. Methods: Overall, 148 patients presenting with advanced stage ovarian carcinomas were included in this retrospective study, regardless of treatment schedule. These patients were stratified according to the extent of surgery (standard or radical). Complete cytoreduction at the time of debulking surgery could not be carried out in all cases. Results: Among our study population (n = 148), 96 patients underwent standard procedures (SPs) and 52 underwent radical surgeries (RP). Patients in the SP group had a lower Peritoneal Index Cancer (PCI) at baseline (12.6 vs. 14.9; p = 0.049). After PCI normalization, we observed similar OS in the SP and RP groups (39.7 vs. 43.1 months; p = 0.737), while patients in the SP group had a higher rate of residual disease >10 mm (p < 10−3). Patients in the RP group had an increased rate of relapse (p = 0.005) but no difference in disease-free survival compared with the SP group (22.2 for SP vs. 16.3 months; p = 0.333). Residual disease status did not impact survival outcomes. Conclusions: In the context of non-resectable, advanced stage ovarian cancer, standard surgery seems as beneficial as radical surgery regarding survival outcomes and should be considered to reduce surgery-associated morbidity. © 2015 Society of Surgical Oncology

Objective Our aim was to review the profile of vintafolide (EC145) and its rationale for use in platinum-resistant ovarian cancer. First we investigated the folate receptors (FRs), folate’s pathway into cells, and its expression in normal and cancerous cells, before detailing the mechanism of action of vintafolide, its clinical applications, and the results of different study phases. Materials and methods A literature search was conducted through PubMed/Medline, Google, ClinicalTrials.gov and websites of pharmaceutical companies. Only articles in English were selected. All articles investigating folate receptor expression in ovarian cancer were selected first, than articles reviewing platinum resistance. Papers about vintafolide were collected, while those talking about synthesis and biochemistry concerns were excluded. The different Phase I and II studies were read, and an update on the website of pharmaceuticals companies were added. Results FR is a bundle-membrane receptor that is expressed normally in some normal tissues on the apical surface of cells, but highly expressed in ovarian cancer cells (>80%). It collects folate through endocytosis. Chemotherapy does not modify its expression in ovarian cancer cells, and its expression appears to be mostly associated with a poor prognosis and platinum resistance. Vintafolide is a folate-desacetylvinblastine monohydrazide conjugate, allowing a liberation of the drug into the cytoplasm of cancerous cells via the FR-α (FRα) and endocytosis, with high specificity. Phase I studies showed a 2.5 mg bolus dose to be nontoxic, with moderately adverse events. Phase II clinical trials for the first time demonstrated a statistically significant improvement in disease-free survival in patients with platinum-resistant ovarian cancer, and in those with a very poor prognosis who had already received three to four lines of systemic chemotherapy. The greater benefits were observed in patients with highly expressed FRα. Conclusion Vintafolide is a promising targeted agent for recurrent platinum-resistant ovarian cancer, first, thanks to its mechanism of action and the characteristics of FRα in ovarian cancer, and, second, because of the favorable results observed in the first clinical trials on platinum-resistant ovarian cancer. Phase III clinical trials are currently ongoing and are expected to confirm these results.