Publications by authors named "Frédéric Guyon"

58 Publications

[National certification for gynecological cancer surgery].

Bull Cancer 2021 Jun 30. Epub 2021 Jun 30.

Société européenne d'oncologie gynécologique, 7, allée du Niger, 31000 Toulouse, France.

Objective: In France, we are lacking an identified pathway for training in gynaecological cancer surgery. The four competent French learned societies: the SFOG, the CNGOF, the SFCO and the SCGP supported by the CNU of Obstetrics & Gynaecology, and UNICANCER agreed to materialize this course and attest it by a certification awarded by a national jury.

Material And Methods: The national committee of certification in gynaecological oncology made up of ten members, representing the 6 concerned organizations, set itself five objectives: the definition of the eligibility criteria for training centres; the determination of a check-list to be filled by the candidate; the determination of a targeted curriculum for the training in gynecological oncological surgery; the determination of the assets necessary for the certification of a candidate already in practice; and the practical organization of the certification.

Results: Criteria for approval of centres for training included 150 gynaecological cancer cases per year, among which 100 excisional surgeries, including twenty advanced-stage ovarian cancers. For certification of candidate who followed the curriculum established by the committee or by validation of prior experience for an actual practitioner, a candidate must validate a logbook and fill out a checklist including four parts: theoretical and practical training; research and publications; teaching and subscription to a continuing education program. The accomplished elements of the logbook and the checklist will be evaluated by a score. The first certification session is planned for the end of 2021.
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http://dx.doi.org/10.1016/j.bulcan.2021.03.019DOI Listing
June 2021

Diffusion-weighted MRI and PET/CT reproducibility in epithelial ovarian cancers during neoadjuvant chemotherapy.

Diagn Interv Imaging 2021 Jun 7. Epub 2021 Jun 7.

Department of nuclear medicine, Institut Bergonié, Comprehensive Cancer Center of Nouvelle-Aquitaine, 33000 Bordeaux, France.

Purpose: To investigate the reproducibility of diffusion-weighted (DW) MRI and F-Fluorodeoxyglucose (F-FDG)-Positron emission tomography/CT (PET/CT) in monitoring response to neoadjuvant chemotherapy in epithelial ovarian cancer.

Materials And Methods: Ten women (median age, 67 years; range: 41.8-77.3 years) with stage IIIC-IV epithelial ovarian cancers were included in this prospective trial (NCT02792959) between 2014 and 2016. All underwent initial laparoscopic staging, four cycles of carboplatine-paclitaxel-based chemotherapy and interval debulking surgery. PET/CT and DW-MRI were performed at baseline (C0), after one cycle (C1) and before surgery (C4). Two nuclear physicians and two radiologists assessed five anatomic sites for the presence of ≥1 lesion. Target lesions in each site were defined and their apparent diffusion coefficient (ADC), maximal standardized uptake value (SUV-max), SUV-mean, SUL-peak, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were monitored (i.e., 10 patients ×5 sites ×3 time-points). Their relative early and late changes were calculated. Intra/inter-observer reproducibilities of qualitative and quantitative analysis were estimated with Kappa and intra-class correlation coefficients (ICCs).

Results: For both modalities, inter- and intra-observer agreement percentages were excellent for initial staging but declined later for DW-MRI, leading to lower Kappa values for inter- and intra-observer variability (0.949 and 1 at C0, vs. 0.633 and 0.643 at C4, respectively) while Kappa values remained>0.8 for PET/CT. Inter- and intra-observer ICCs were>0.75 for SUV-max, SUL-peak, SUV-mean and their change regardless the time-point. ADC showed lower ICCs (range: 0.013-0.811). ANOVA found significant influences of the evaluation time, the measurement used (ADC, SUV-max, SUV-mean, SUV-max, SUL-peak, MTV or TLG) and their interaction on ICC values (P=0.0023, P<0.0001 and P =0.0028, respectively).

Conclusion: While both modalities demonstrated high reproducibility at baseline, only SUV-max, SUL-peak, SUV-mean and their changes maintained high reproducibility during chemotherapy.
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http://dx.doi.org/10.1016/j.diii.2021.05.007DOI Listing
June 2021

FDG-PET/CT and Para-Aortic Staging in Endometrial Cancer. A French Multicentric Study.

J Clin Med 2021 Apr 17;10(8). Epub 2021 Apr 17.

Department of Gynaecology and Obstetrics, CHU Limoges, 87042 Limoges, France.

Background: FDG-PET/CT is a noninvasive examination that could be helpful for the management of endometrial cancer. The aim of this study was to evaluate the performance of FDG-PET/CT in assessing para-aortic lymph-node involvement in high-risk endometrial cancer.

Methods: We performed a retrospective multicenter study including all patients who had a high-risk endometrial cancer with a preoperative FDG-PET/CT and a para-aortic lymphadenectomy (PAL) between 2009 and 2019. The main objective was to evaluate the overall performance of FDG-PET/CT. The secondary objectives were to evaluate its performances according to the histological type and according to FDG-PET/CT date (before or after hysterectomy), and to compare its overall performance with that of the MRI scan.

Results: We included 200 patients from six different centers. After the false positive FDG-PET/CT was reread by nuclear physicians, FDG-PET/CT had a sensitivity of 61.8%, a specificity of 89.7%, a positive predictive value of 69.4%, a negative predictive value of 86.1%, and an AUC of 0.76. There were no statistically significant differences in the performances according to either histological type and or FDG-PET/CT date. The sensitivity of FDG-PET/CT was better than that of MRI ( < 0.01), but the specificity was not ( = 0.82).

Conclusion: Currently, FDG-PET/CT alone cannot replace PAL for the lymph node evaluation of high-risk endometrial cancers. It seems essential to reread it in multidisciplinary meetings before validating the therapeutic management of patients, particularly in the case of isolated para-aortic involvement.
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http://dx.doi.org/10.3390/jcm10081746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074207PMC
April 2021

Adherence to French and ESGO Quality Indicators in Ovarian Cancer Surgery: An Ad-Hoc Analysis from the Prospective Multicentric CURSOC Study.

Cancers (Basel) 2021 Mar 30;13(7). Epub 2021 Mar 30.

Department of Gynecologic Oncology, Agostino Gemelli University Hospital, 00168 Rome, Italy.

Background: Quality Indicators for ovarian cancer (OC) have been developed by the European Society of Gynaecological Oncology (ESGO) and by the French National Cancer Institute (Institut National du Cancer, INCa). The aim of the study was to characterize OC care distribution in France by case-volume and to prospectively evaluate the adherence of high-volume institutions to INCa/ESGO quality indicators.

Methods: The cost-utility of radical surgery in ovarian cancer (CURSOC) trial is a prospective, multicenter, comparative and non-randomized study that includes patients with stage IIIC-IV epithelial OC treated in nine French health care tertiary institutions. Adherence to institutional quality indicators were anonymously assessed by an independent committee. OC care distribution in France were provided by the nationwide database of hospital procedures.

Results: More than half of patients are treated in low-volume institutions. Among the nine high-volume centers participating in the study, four (44.4%) met all institutional INCa/ESGO quality indicators. The other five (55.6%) did not fulfil one of the quality indicator criteria.

Conclusions: Access to high-volume OC providers in France is restricted to a minority of patients, and yet half of the referral institutions included in this study failed to meet all recommended institutional quality indicators. It is mandatory that national authorities work both to improve OC centralization and to incorporate quality assurance programs into certified centers.
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http://dx.doi.org/10.3390/cancers13071593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037412PMC
March 2021

Sentinel lymph node biopsy and morbidity outcomes in early cervical cancer: Results of a multicentre randomised trial (SENTICOL-2).

Eur J Cancer 2021 May 24;148:307-315. Epub 2021 Mar 24.

Anne-Sophie Bats, Hôpital Européen Georges Pompidou, Service de Gynécologie, 20-40 Rue Leblanc, 75908 Paris Cedex 15, France.

Introduction: Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the detection of metastatic disease, but benefits of omitting pelvic lymph node dissection in terms of decreased morbidity have not been demonstrated.

Materials And Methods: In an open-label study, patients with early cervical carcinoma (FIGO 2009 stage IA2 to IIA1) were randomly assigned to SN resection alone (SN arm) or SN and pelvic lymph node dissection (SN + PLND arm). SN resection was followed by radical surgery of the tumour (radical hysterectomy or radical trachelectomy). The primary end-point was morbidity related to the lymph node dissection; 3-year recurrence-free survival was a secondary end-point.

Results: A total of 206 patients were eligible and randomly assigned to the SN arm (105 patients) or SN + PLND arm (101 patients). Most patients had stage IB1 lesion (87.4%). No false-negative case was observed in SN + PLND arm. Lymphatic morbidity was significantly lower in the SN arm (31.4%) than in the SN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively). However, there was no significant difference in the proportion of patients with significant lymphoedema between the two groups. During the 6-month postoperative period, the difference in morbidity decreased over time. The 3-year recurrence-free survival was not significantly different (92.0% in SN arm and 94.4% in SN + PLND arm).

Conclusion: SN resection alone is associated with early decreased lymphatic morbidity when compared with SN + PLND in early cervical cancer.
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http://dx.doi.org/10.1016/j.ejca.2021.02.009DOI Listing
May 2021

Molecular Characterization of Ovarian Yolk Sac Tumor (OYST).

Cancers (Basel) 2021 Jan 9;13(2). Epub 2021 Jan 9.

Centre Léon Berard (CLB), 69008 Lyon, France.

Most patients with malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and chemotherapy provides curative treatment; however, patients with yolk sac tumors (OYSTs) have a significantly worse prognosis. OYSTs are rare tumors and promising results are expected with the use of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens. We initiated a project in collaboration with EORTC SPECTA, to explore the molecular characteristics of OYSTs. The pilot project used retrospective samples from ten OYST relapsed and disease-free patients. Each patient had a molecular analysis performed with FoundationOne CDx describing the following variables according to the Foundation Medicine Incorporation (FMI): alteration type (SNV, deletion), actionable gene alteration, therapies approved in EU (for patient's tumor type and other tumor types), tumor mutational burden (TMB), and microsatellite instability (MSI) status. A total of 10 patients with OYST diagnosed between 2007 and 2017 had a molecular analysis. A molecular alteration was identified in four patients (40%). A subset of three patients (33.3% of all patients) harbored targetable oncogenic mutations in , , . Two patients at relapse harbored a targetable mutation. This retrospective study identifies clinically relevant molecular alterations for all relapsed patients with molecular analysis. Dedicated studies are needed to demonstrate the efficacy of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens and to explore the potential relationship of a molecular alteration and patient outcome.
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http://dx.doi.org/10.3390/cancers13020220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826864PMC
January 2021

Intraoperative detection of second inferior vena cava during para-aortic lymphadenectomy for advanced-staged ovarian cancer: Lessons to be learned.

Clin Case Rep 2020 Sep 8;8(9):1845-1846. Epub 2020 Jun 8.

Gynaecologic Oncology Unit Institut Bergonie Bordeaux France.

As the presence of second inferior vena cava may alter the extent of para-aortic lymphadenectomy, early preoperative imaging diagnosis is of great significance to avoid intraoperative difficulties.
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http://dx.doi.org/10.1002/ccr3.2965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495822PMC
September 2020

SFOG Campus, A new group is born!

J Gynecol Obstet Hum Reprod 2020 Sep 9:101903. Epub 2020 Sep 9.

Institut Bergonie - Bordeaux, France.

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http://dx.doi.org/10.1016/j.jogoh.2020.101903DOI Listing
September 2020

A multivariate analysis of the prognostic impact of tumor burden, surgical timing and complexity after complete cytoreduction for advanced ovarian cancer.

Gynecol Oncol 2020 09 22;158(3):614-621. Epub 2020 Jul 22.

Department of Surgical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse (IUCT), Oncopole, Toulouse, France; INSERM CRCT 1, Toulouse, France. Electronic address:

Objective: To assess the survival benefit of primary debulking surgery (PDS) compared to interval debulking surgery (IDS) after complete cytoreduction (CC-0) or cytoreduction to minimal residual disease (CC-1) in advanced ovarian cancer. Secondary objective was to evaluate the effect of tumor load and surgical complexity on patients' survival.

Methods: A retrospective multicentric study was designed, including patients with IIIC-IV FIGO stage ovarian cancer who underwent PDS or IDS with CC-0 or CC-1 from January 2008 to December 2015 in four high-volume institutions. Patients were classified in three groups: PDS, IDS after 3-4 cycles of neoadjuvant chemotherapy (NACT), and IDS after 6 cycles. Disease-free survival (DFS) and overall survival (OS) were estimated. Univariable and multivariable analyses were conducted.

Results: We included 549 patients, 175 (31.9%) underwent PDS, 224 (40.8%) had IDS after 3-4 cycles of NACT, and 150 (27.3%) underwent IDS after 6 cycles. Median DFS in PDS, IDS at 3-4 cycles and IDS at 6 cycles were 23.0 months (95%CI = [20.0-29.3]), 18.0 months (95%CI = [15.9-20.0]) and 17.1 months (95%CI = [15.0-20.9]), respectively; p < .001. Median OS were 84.0 months (95%CI = [68.3-111.0]), 50.7 months (95%CI = [44.6-59.5]) and 47.5 months (95%CI = [39.3-52.9]), respectively; p < .001. In multivariable analysis, high peritoneal cancer index score and NACT were negatively associated to DFS and OS. Surgical complexity and CC-1 were negatively associated to DFS.

Conclusion: PDS offered a survival gain of almost three years compared to IDS in patients with minimal or no residual disease after surgery. PDS should remain the standard of care for advanced ovarian cancer.
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http://dx.doi.org/10.1016/j.ygyno.2020.06.495DOI Listing
September 2020

Combined pelvic and para-aortic is superior to only pelvic lymphadenectomy in intermediate and high-risk endometrial cancer: a systematic review and meta-analysis.

Arch Gynecol Obstet 2020 07 28;302(1):249-263. Epub 2020 May 28.

3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloníki, Greece.

Background: Lymph node metastasis is a principal prognostic factor for the treatment of endometrial cancer. Added value of para-aortic lymphadenectomy to only pelvic lymphadenectomy for intermediate/high-risk endometrial cancer patients remains controversial.

Objective: A systematic review and meta-analysis was performed to assess the impact of combined pelvic and para-aortic lymph node dissection (PPALND) compared to only pelvic lymph node dissection (PLND) on survival outcomes of intermediate and/or high-risk patients.

Study Design: The systematic review and meta-analysis adhered to the PRISMA guidelines for meta-analyses of interventional studies. Pubmed, Scopus, EMBASE and Cochrane were searched up to April 20, 2018. Included studies were those comparing high-risk endometrial cancer patients that had performed pelvic and para-aortic lymph node dissection (PPALND) vs. only pelvic lymph node dissection (PLND) apart from standard procedure (total hysterectomy with bilateral salpingo-oophorectomy, TAHBSO). Primary outcomes of the study were overall survival and disease-free survival rates. Methodological quality of the included studies was assessed using the ROBINS-I tool. Overall quality of the evidence for the primary and secondary outcomes was evaluated as per GRADE guideline using the GRADE pro GD tool.

Results: There were 13 studies identified with 7349 patients included. All studies were retrospective observational as no RCTs or prospective studies adhering to inclusion criteria were retrieved. Combined pelvic and para-aortic lymphadenectomy was associated with 46% decreased risk for death (HR 0.54, 95% CI 0.35-0.83, I = 62.1%) and 49% decreased risk for recurrence (HR 0.51, 95% CI 0.28-0.93). It was also associated with increased 5-year OS rate (RR 1.13, 95% CI 1.04-0.24, I = 57.3%) and increased 5-year DFS rate (RR 1.23, 95% CI 1.14-1.31, I = 85.5) compared with only pelvic lymphadenectomy.

Conclusion: Combined pelvic and para-aortic lymphadenectomy is associated with improved survival outcomes compared with only pelvic lymphadenectomy in women with intermediate/high-risk endometrial cancers. Further prospective studies should be performed.
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http://dx.doi.org/10.1007/s00404-020-05587-2DOI Listing
July 2020

[Impact of the LACC study. A SFOG survey].

Bull Cancer 2020 May 31;107(5):551-555. Epub 2020 Mar 31.

Département de chirurgie, Gustave Roussy Cancer Campus, 94800 Villejuif, France.

Introduction: The LACC (Laparoscopic Approach to Cervical Cancer Trial) study, released in 2018, described oncological findings in favour of open surgery compared to the minimally invasive pathway in the management of early stage cervical cancers. Our aim was to assess the impact of this study on surgical practices in France.

Method: Online questionnaire, consisting of 13 questions addressed to gynecology oncology french society (SFOG) surgeons.

Results: Forty questionnaires were collected. The median annual number of radical hysterectomy was 5 (0-20). Prior to the study, 92.5 % of cervical cancer patients had radical hysterectomy by minimally invasive surgery. In case of laparoscopy or robot, the uterine manipulator was used in 67.6 % and the colpotomy was performed intra-abdominally (78.4 %). After the LACC study, 60 % changed their practice. Open surgery was favored by 75 % of those who modified their practice. Among those continuing to perform minimally invasive surgeries, the manipulator and the intracorporeal colpotomy were discontinued. One-third of surgeons have changed their surgical practice for endometrial cancer in parallel.

Conclusion: The results of the LACC study led to a change in surgical practices with an increase in open surgery and a stop in the use of the uterine manipulator and the laparoscopic/robotic intracorporeal colpotomy in the surgical management of early stage of cervical cancer.
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http://dx.doi.org/10.1016/j.bulcan.2020.02.012DOI Listing
May 2020

Fertility and prognosis of borderline ovarian tumor after conservative management: Results of the multicentric OPTIBOT study by the GINECO & TMRG group.

Gynecol Oncol 2020 04;157(1):29-35

Institut Curie, St Cloud, France; Inserm U900, Institut Curie, St Cloud, France. Electronic address:

Objectives: Description of fertility and prognosis of patients with borderline ovarian tumor (BOT) treated by fertility-sparing surgery through a longitudinal study from the French national cancer network.

Methods: All consecutive patients diagnosed with BOT from the French National Network dedicated to Ovarian Malignant Rare Tumors from 2010 and 2017 were selected. In 2018, an update was made by sending a questionnaire regarding recurrence and fertility to patients aged under 43 years at diagnosis and treated conservatively. We compared the characteristics of the patients with/without recurrence and with/without live birth.

Results: Fifty-two patients aged 18 to 42 years presented a desire of pregnancy. Thirty patients (58%) presented a FIGO IA tumor, and 20 patients were treated by bilateral cystectomies (38%). We observed at least one live birth for 33 patients (63%) and local recurrences in 20 patients (38%). Both recurrence and live birth in 17 patients (33%) were reported, with recurrence occurring before pregnancy, after a second fertility-sparing treatment, in half of the cases. No factors associated with recurrence or live birth in this study were identified. Moreover, in this population, both recurrence and live birth were independent of age, with a linear risk along time. Disease-free survival was worse for patients treated with bilateral cystectomy (n = 20, 38%), with no difference in terms of fertility.

Conclusion: Two third of the patients experienced life birth after conservation surgery. We did not highlight an age/time from surgery for which the risk of recurrence outweighs the chance of pregnancy and to radicalize surgery. Moreover, almost a quarter of the live birth occurred after recurrence, with no more further event to date in these patients. The results encourage to consider a second fertility-sparing surgery after local borderline recurrence in the case of pregnancy desire. All these decisions must be discussed in specialized multidisciplinary boards.
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http://dx.doi.org/10.1016/j.ygyno.2019.12.046DOI Listing
April 2020

Frozen section examination of sentinel lymph nodes can be used as a decisional tool in the surgical management of early cervical cancer.

Int J Gynecol Cancer 2020 03 6;30(3):358-363. Epub 2020 Jan 6.

Surgical Oncology, Institut Bergonié, Bordeaux, Aquitaine, France.

Introduction: Sentinel lymph node (SLN) detection has been shown to be accurate in detecting lymph node involvement in early-stage cervical cancer. The objective of this study was to evaluate the accuracy of frozen section examination in the assessment of SLN status, with the aim of adequately driving the intra-operative decision.

Methods: We designed a retrospective study including patients from two comprehensive cancer centers between January 2001 and December 2018 with early-stage cervical cancer (IA1-IB2 according to International Federation of Gynecology and Obstetrics (FIGO) 2018) undergoing SLN dissection. The SLN procedure was performed using a cervical injection with technetium-99m combined with blue dye or indocyanine green in most cases.

Results: A total of 176 patients fulfilled inclusion criteria. Bilateral mapping was detected in 153 (86.7%) of them. Nineteen of these patients (12.4%) had SLN involvement: 13 with macrometastases, three with micrometastases and three with isolated tumor cells (ITC). Macrometastatic disease was missed on frozen section in 3/13 FIGO 2018 stage IIIC patients. The three patients with ITC were also missed by frozen section examination.Considering only macrometastases as lymph node involvement, frozen section sensitivity was 76.9% (95% CI 49.7 to 91.8) and negative predictive value (NPV) was 97.9% (95% CI 94.0 to 99.3) in patients with bilateral detection. Including micrometastases, sensitivity was 81.2% (95% CI 57.0 to 93.4) and NPV remained at 97.9% (95% CI 93.9 to 99.3).

Conclusions: With a prevalence of final-stage IIIC in patients with pre-operative early-stage cervical cancer of the order of 10% in this series, the NPV of frozen section examination of SLN is very high, with an inferior limit of the CI superior to 94%. Diagnostic accuracy remains acceptable even if micrometastases are considered. The impact of missed ITC has not been established. Frozen section examination can be incorporated in the intra-operative decision algorithm.
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http://dx.doi.org/10.1136/ijgc-2019-000904DOI Listing
March 2020

Comparison of postoperative complications and quality of life between patients undergoing continent versus non-continent urinary diversion after pelvic exenteration for gynecologic malignancies.

Int J Gynecol Cancer 2020 02 2;30(2):233-240. Epub 2019 Dec 2.

Institut Claudius Regaud, Toulouse, Occitanie, France

Background: Pelvic exenteration and its reconstructive techniques have been associated with high postoperative morbidity and a negative impact on patient quality of life. The aim of our study was to compare postoperative complications and quality of life in patients undergoing continent compared with non-continent urinary diversion after pelvic exenteration for gynecologic malignancies.

Methods: We designed a multicenter study of patients from 10 centers who underwent an anterior or total pelvic exenteration with urinary reconstruction for histologically confirmed persistent or recurrent gynecologic malignancy after previous treatment with radiotherapy. From January 2005 to September 2008, we included patients retrospectively, and from September 2008 to May 2009, patients were included prospectively which allowed collection of quality of life data. Demographic, surgical, and follow-up data were analyzed. Postoperative complications were classified according to the Clavien-Dindo classification. Quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C30 (V.3.0) and EORTC-QLQ-OV28 quality of life questionnaires. We compared patients who underwent a continent urinary diversion with those who underwent a non-continent reconstruction.

Results: We included 148 patients, 92 retrospectively and 56 prospectively. Among them, 77.4% had recurrent disease and 22.6% persistent disease after the primary treatment. In 70 patients, a urinary continent diversion was performed, and 78 patients underwent a non-continent diversion. Median age of the continent and incontinent groups was 53.5 (range 33-78) years and 57 (26-79) years, respectively. There were no significant differences between the continent and non-continent groups in median length of hospitalization (28.5 vs 26 days, P=0.19), postoperative grade III-IV complications (42.9% vs 42.3%, P=0.95), complications needing surgical (27.9% vs 34.6%, P=0.39) or radiological (14.7% vs 12.8%, P=0.74) intervention, and complication type (digestive (23.2% vs 16.7%, P=0.32) and urinary (15.9% vs 16.7%, P=0.91)). There were no significant differences between the groups in global health, global quality of life, and body image perception scores 1 year after surgery.

Conclusion: Continent and incontinent urinary reconstructions are equivalent in terms of postoperative complications and quality of life scores.
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http://dx.doi.org/10.1136/ijgc-2019-000863DOI Listing
February 2020

The Nanocind Signature Is an Independent Prognosticator of Recurrence and Death in Uterine Leiomyosarcomas.

Clin Cancer Res 2020 02 3;26(4):855-861. Epub 2019 Dec 3.

Oncosarc, INSERM UMR1037, Cancer Research Center of Toulouse, Toulouse, France.

Purpose: Uterine leiomyosarcoma, which accounts for 7% of all soft-tissue sarcomas and 1%-3% of all uterine malignancies, is an aggressive tumor responsible for a significant proportion of uterine cancer-related deaths. While Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage is the most important prognostic factor, metastatic and relapse rates at stage I exceed 50% so it is currently impossible to predict the clinical outcome of stage I leiomyosarcomas. In 2010, our team published a transcriptomic signature composed of 67 genes related to chromosome biogenesis, mitosis control, and chromosome segregation. It has demonstrated its prognostic value in many cancer types and was recently successfully applied to formalin-fixed, paraffin-embedded sarcomas by NanoCind on NanoString technology, making another step forward toward its use in routine practice.

Experimental Design: Sixty uterine leiomyosarcomas at any stage, including 40 localized in the uterus (stage I), were analyzed with the NanoCind (CINSARC with NanoString) signature. Its prognostic value was evaluated for overall survival and relapse-free survival and compared in multivariate analysis with other prognostic markers like FIGO staging and genomic index.

Results: The NanoCind signature was able to split the heterogeneous group of uterine leiomyosarcomas of any stage including stage I into two distinct groups with different relapse-free survival and overall survival. These results were validated on an independent cohort of uterine leiomyosarcomas in The Cancer Genome Atlas consortium.

Conclusions: The NanoCind signature is a powerful prognosticator that outperforms FIGO staging and the genomic index. The CINSARC signature is platform independent and "ready to use" and should now be used for randomization in future therapeutic trials.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-2891DOI Listing
February 2020

[Management of the nodal disease in vulvar cancers. The ESGO guidelines].

Bull Cancer 2020 Jun 2;107(6):715-720. Epub 2019 Oct 2.

Institut Bergonié, 229, cours de l'Argonne, 33000 Bordeaux, France.

The European Society of Gynaecologic Oncology (ESGO) guidelines cover the whole field of common clinical situations in gynecologic oncology. Their elaboration follows a strict process including a systematic review of the literature, the setting up of a group of expert on the basis of scientific production, geographical balance, and multidisciplinarity, and an external review by users and patients. The recommendations for the management of vulvar cancer were elaborated in 2015 and published in 2017. They are available in open access on the ESGO website, and can be incorporated in clinical practice using the free ESGO guidelines smartphone application. This review is a selection of the sections addressing the diagnostic and strategical aspects of the management of lymph nodal disease in vulvar cancer. An additional review of the recent literature published since 2015 has been carried out. The management of nodal disease in vulvar cancer encompasses a diagnostic and a therapeutic component. Clinical and imaging assessment still play a major role, whilst the identification of the sentinel node is currently a mainstay of assessment of the nodal status in early vulvar cancer. The therapeutic component is based on the rational use of full lymph node dissection and (chemo)radiation.
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http://dx.doi.org/10.1016/j.bulcan.2019.06.010DOI Listing
June 2020

TRUST: Trial of Radical Upfront Surgical Therapy in advanced ovarian cancer (ENGOT ov33/AGO-OVAR OP7).

Int J Gynecol Cancer 2019 10 15;29(8):1327-1331. Epub 2019 Aug 15.

AGO Study Group and Department of Obstetrics and Gynecology, University Hospital, Ludwig Maximilians University Munich, Munich, Bayern, Germany.

Background: Primary cytoreductive surgery followed by chemotherapy has been considered standard management for patients with advanced ovarian cancer over decades. An alternative approach of interval debulking surgery following neoadjuvant chemotherapy was subsequently reported by two randomized phase III trials (EORTC-GCG, CHORUS), which were criticized owing to important limitations, especially regarding the rate of complete resection.

Primary Objective: To clarify the optimal timing of surgical therapy in advanced ovarian cancer.

Study Hypothesis: Primary cytoreductive surgery is superior to interval cytoreductive surgery following neoadjuvant chemotherapy for overall survival in patients with advanced ovarian cancer.

Trial Design: TRUST is an international open, randomized, controlled multi-center trial investigating overall survival after primary cytoreductive surgery versus neoadjuvant chemotherapy and subsequent interval cytoreductive surgery in patients with FIGO stage IIIB-IVB ovarian, tubal, and peritoneal carcinoma. To guarantee adequate surgical quality, participating centers need to fulfill specific quality assurance criteria (eg, ≥50% complete resection rate in upfront surgery for FIGO IIIB-IVB patients, ≥36 debulking-surgeries/year) and agree to independent audits by TRUST quality committee delegates. Patients in the primary cytoreductive surgery arm undergo surgery followed by 6 cycles of platinum-based chemotherapy, whereas patients in the interval cytoreductive surgery arm undergo 3 cycles of neoadjuvant chemotherapy after histologic confirmation of the disease, followed by interval cytoreductive surgery and subsequently, 3 cycles of platinum-based chemotherapy. The intention of surgery for both groups is complete tumor resection according to guideline recommendations.

Major Inclusion/exclusion Criteria: Major inclusion criteria are suspected or histologically confirmed, newly diagnosed invasive epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma FIGO stage IIIB-IVB (IV only if resectable metastasis). Major exclusion criteria are non-epithelial ovarian malignancies and borderline tumors; prior chemotherapy for ovarian cancer; or abdominal/pelvic radiotherapy.

Primary Endpoint: Overall survival.

Sample Size: 772 patients.

Estimated Dates For Completing Accrual And Presenting Results: Accrual completion approximately mid-2019, results are expected after 5 years' follow-up in 2024.

Trial Registration: NCT02828618.
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http://dx.doi.org/10.1136/ijgc-2019-000682DOI Listing
October 2019

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

Eur J Cancer 2019 07 3;116:35-44. Epub 2019 Jun 3.

Recommandations pour La Pratique Clinique, Nice-Saint-Paul, 06000, France.

Introduction: Rare ovarian tumours include complex borderline ovarian tumours, sex-cord tumours, germ cell tumours and rare epithelial tumours. Indications and modalities of fertility preservation (FP), infertility management, contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and experts in reproductive medicine and gynaecology have built guidelines on FP, contraception and menopause hormone therapy in women treated for ovarian rare tumours.

Material And Methods: A panel of 35 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review and then rated through two successive rounds.

Results: Thirty-five recommendations were identified, concerning indications for FP, contraindications for ovarian stimulation, contraceptive options and menopause hormone therapy for each tumour type.

Discussion: Overall, caution has been recommended in the case of potentially hormone-sensitive tumours such as sex-cord tumours, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumours.

Conclusion: In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.
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http://dx.doi.org/10.1016/j.ejca.2019.04.018DOI Listing
July 2019

PatchSearch: a web server for off-target protein identification.

Nucleic Acids Res 2019 07;47(W1):W365-W372

Université Paris Diderot, Sorbonne Paris Cité, INSERM UMRS-973, Molécules Thérapeutiques in silico (MTi), F-75205 Paris, France.

The large number of proteins found in the human body implies that a drug may interact with many proteins, called off-target proteins, besides its intended target. The PatchSearch web server provides an automated workflow that allows users to identify structurally conserved binding sites at the protein surfaces in a set of user-supplied protein structures. Thus, this web server may help to detect potential off-target protein. It takes as input a protein complexed with a ligand and identifies within user-defined or predefined collections of protein structures, those having a binding site compatible with this ligand in terms of geometry and physicochemical properties. It is based on a non-sequential local alignment of the patch over the entire protein surface. Then the PatchSearch web server proposes a ligand binding mode for the potential off-target, as well as an estimated affinity calculated by the Vinardo scoring function. This novel tool is able to efficiently detects potential interactions of ligands with distant off-target proteins. Furthermore, by facilitating the discovery of unexpected off-targets, PatchSearch could contribute to the repurposing of existing drugs. The server is freely available at http://bioserv.rpbs.univ-paris-diderot.fr/services/PatchSearch.
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http://dx.doi.org/10.1093/nar/gkz478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602448PMC
July 2019

Clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome.

EBioMedicine 2019 May 2;43:253-260. Epub 2019 Apr 2.

Institut de cancérologie de l'Ouest - site Paul Papin (ICO) 15, Rue André Boquel, 49055 Angers, France.

Background: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome.

Methods: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome.

Findings: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters.

Interpretation: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810.
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http://dx.doi.org/10.1016/j.ebiom.2019.03.069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562019PMC
May 2019

Uterine and vaginal sarcomas resembling fibrosarcoma: a clinicopathological and molecular analysis of 13 cases showing common NTRK-rearrangements and the description of a COL1A1-PDGFB fusion novel to uterine neoplasms.

Mod Pathol 2019 07 16;32(7):1008-1022. Epub 2019 Mar 16.

Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK.

Mesenchymal neoplasms of the uterus (corpus and cervix) encompass a heterogeneous group of tumors with differing morphologies, immunophenotypes and molecular alterations. With the advent of modern molecular techniques, such as next generation sequencing, newly defined genetic abnormalities are being reported in this group of neoplasms. Herein we report the clinicopathological and molecular features of a series of 13 spindle cell sarcomas of the uterus and vagina (10 cervix, 2 uterine corpus, 1 vagina) with morphology resembling fibrosarcoma. After targeted RNA-sequencing, dual FISH fusion and array-CGH analysis, 7 of 13 tumors exhibited NTRK rearrangements (6 TPM3-NTRK1 and 1 EML4-NTRK3) and 3 a COL1A1-PDGFB fusion; in the other 3 neoplasms, all of which were positive with S100 (2 diffuse, 1 focal), we identified no rearrangement. All the NTRK fusion-positive sarcomas were located in the cervix and exhibited diffuse staining with Trk while all the other neoplasms were negative. CD34 was diffusely positive in all 3 of the COL1A1-PDGFB fusion sarcomas. The latter molecular abnormality is identical to that commonly found in dermatofibrosarcoma protuberans and has not been reported previously in uterine mesenchymal neoplasms. We suggest that uterine sarcomas with a morphology resembling fibrosarcoma (and in which leiomyosarcoma and the known molecularly confirmed high-grade endometrial stromal sarcomas have been excluded) can be divided into 3 groups:- an NTRK fusion group, a COL1A1-PDGFB fusion group and a group containing neither of these molecular abnormalities which, on the basis of positive staining with S100, could be tentatively classified as malignant peripheral nerve sheath tumor, although additional molecular studies may identify specific genetic alterations necessitating a nomenclature change. We suggest a diagnostic algorithm when reporting such neoplasms. Identification of these newly described fusion-associated sarcomas is important given the potential for targeted treatments.
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http://dx.doi.org/10.1038/s41379-018-0184-6DOI Listing
July 2019

GREB1-CTNNB1 fusion transcript detected by RNA-sequencing in a uterine tumor resembling ovarian sex cord tumor (UTROSCT): A novel CTNNB1 rearrangement.

Genes Chromosomes Cancer 2019 03 7;58(3):155-163. Epub 2019 Jan 7.

Cancer Research Center of Toulouse, Oncosarc, INSERM UMR1037, Toulouse, France.

Mutations of CTNNB1 have been implicated in tumorigenesis in many organs. However, tumors harboring a CTNNB1 translocation are extremely rare and this translocation has never been reported in a uterine mesenchymal neoplasm. We report a novel translocation t(2;3)(p25;p22) involving the GREB1 (intron 8) and CTNNB1 (exon 3) in a uterine tumor resembling ovarian sex cord tumor (UTROSCT), which exhibited extrauterine metastasis. The translocation detected by RNA-sequencing was validated by RT-PCR, and resulted in nuclear expression of β-catenin. Juxtapositioning with GREB1, which is overexpressed in response to estrogens, resulted in overexpression of a truncated and hypophosphorylated nuclear β-catenin in the primary and recurrent tumors. This accumulation of nuclear β-catenin results in a constitutive activation of the Wnt/β-catenin signaling pathway with a major oncogenic effect. The CTNNB1 gene fusion, promoted by an estrogen-responsive gene (GREB1), could be a potential driver of tumorigenesis in this case and a therapeutic target with adapted inhibitors. RT-PCR and immunohistochemistry performed on 11 additional UTROSCTs showed no CTNNB1 fusion transcript or nuclear β-catenin immunoreactivity.
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http://dx.doi.org/10.1002/gcc.22694DOI Listing
March 2019

DaReUS-Loop: accurate loop modeling using fragments from remote or unrelated proteins.

Sci Rep 2018 09 12;8(1):13673. Epub 2018 Sep 12.

Molécules Thérapeutiques in silico, UMR-S973, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot, Sorbonne Paris Cité, RPBS, 75013, Paris, France.

Despite efforts during the past decades, loop modeling remains a difficult part of protein structure modeling. Several approaches have been developed in the framework of crystal structures. However, for homology models, the modeling of loops is still far from being solved. We propose DaReUS-Loop, a data-based approach that identifies loop candidates mining the complete set of experimental structures available in the Protein Data Bank. Candidate filtering relies on local conformation profile-profile comparison, together with physico-chemical scoring. Applied to three different template-based test sets, DaReUS-Loop shows significant increase in the number of high-accuracy loops, and significant enhancement for modeling long loops. A special advantage is that our method proposes a prediction confidence score that correlates well with the expected accuracy of the loops. Strikingly, over 50% of successful loop models are derived from unrelated proteins, indicating that fragments under similar constraints tend to adopt similar structure, beyond mere homology.
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http://dx.doi.org/10.1038/s41598-018-32079-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135855PMC
September 2018

[Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumors: Guidelines from the French national network dedicated to rare gynaecological cancer].

Bull Cancer 2018 Mar;105(3):299-314

Centre François-Baclesse, 3, avenue du Général-Harris, 14076 Caen cedex 5, France.

Introduction: Rare ovarian tumors include complex borderline ovarian tumors, sex-cord tumors, germ cell tumors, and rare epithelial tumors. Indications and modalities of fertility preservation, infertility management and contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and of experts in reproductive medicine and gynaecology have worked on guidelines about fertility preservation, contraception and menopause hormone therapy in women treated for ovarian rare tumors.

Methods: A panel of 39 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review, and then rated through two successive rounds.

Results: Thirty-five recommendations were selected, and concerned indications for fertility preservation, contraindications for ovarian stimulation (in the context of fertility preservation or for infertility management), contraceptive options (especially hormonal ones), and menopause hormone therapy for each tumor type. Overall, prudence has been recommended in the case of potentially hormone-sensitive tumors such as sex cord tumors, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumors.

Discussion: In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.
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http://dx.doi.org/10.1016/j.bulcan.2017.10.032DOI Listing
March 2018

Genome profiling is an efficient tool to avoid the STUMP classification of uterine smooth muscle lesions: a comprehensive array-genomic hybridization analysis of 77 tumors.

Mod Pathol 2018 05 12;31(5):816-828. Epub 2018 Jan 12.

Department of Biopathology, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, France.

The diagnosis of a uterine smooth muscle lesion is, in the majority of cases, straightforward. However, in a small number of cases, the morphological criteria used in such lesions cannot differentiate with certainty a benign from a malignant lesion and a diagnosis of smooth muscle tumor with uncertain malignant potential (STUMP) is made. Uterine leiomyosarcomas are often easy to diagnose but it is difficult or even impossible to identify a prognostic factor at the moment of the diagnosis with the exception of the stage. We hypothesize, for uterine smooth muscle lesions, that there is a gradient of genomic complexity that correlates to outcome. We first tested this hypothesis on STUMP lesions in a previous study and demonstrated that this 'gray category' could be split according to genomic index into two groups. A benign group, with a low to moderate alteration rate without recurrence and a malignant group, with a highly rearranged profile akin to uterine leiomyosarcomas. Here, we analyzed a large series of 77 uterine smooth muscle lesions (from 76 patients) morphologically classified as 19 leiomyomas, 14 STUMP and 44 leiomyosarcomas with clinicopathological and genomic correlations. We confirmed that genomic index with a cut-off=10 is a predictor of recurrence (P<0.0001) and with a cut-off=35 is a marker for poor overall survival (P=0.035). For the tumors confined to the uterus, stage as a prognostic factor was not useful in survival prediction. At stage I, among the tumors reclassified as molecular leiomyosarcomas (ie, genomic index ≥10), the poor prognostic markers were: 5p gain (overall survival P=0.0008), genomic index at cut-off=35 (overall survival P=0.0193), 13p loss including RB1 (overall survival P=0.0096) and 17p gain including MYOCD gain (overall survival P=0.0425). Based on these findings (and the feasibility of genomic profiling by array-comparative genomic hybridization), genomic index, 5p and 17p gains prognostic value could be evaluated in future prospective chemotherapy trials.
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http://dx.doi.org/10.1038/modpathol.2017.185DOI Listing
May 2018

Left Lateral Endosurgical Extraperitoneal Total Hysterectomy with Para-Aortic and Pelvic Lymphadenectomy: A Novel Approach for the Obese Patient with Endometrial Cancer.

J Minim Invasive Gynecol 2018 May - Jun;25(4):730-736. Epub 2017 Dec 8.

Gynecologic Oncology Unit, La Paz University Hospital-IdiPAZ, Madrid, Spain.

Study Objective: To describe the left lateral extraperitoneal approach to perform complete para-aortic and pelvic lymphadenectomy and transverse total hysterectomy from left to right as a novel approach to treat obese patients with endometrial cancer. Laparoscopic management of obese patients represents a challenge for the gynecologic surgeon. The extraperitoneal approach is technically easier in the obese patient because it naturally creates a bowel-free operative field.

Design: A prospective pilot bicentric and descriptive study (Canadian Task Force classification III) evaluating the feasibility and reproducibility of the transverse total hysterectomy and complete lymphadenectomy through left endoscopic extraperitoneal approach in obese patients with endometrial cancer.

Setting: A comprehensive cancer center in Toulouse and a teaching university hospital in Madrid.

Patients: Sixteen consecutive overweight or obese patients (body mass index > 25 kg/m) with high-risk endometrial cancer.

Interventions: Currently, the left extraperitoneal approach is routinely used to perform complete para-aortic and pelvic lymphadenectomy. It provides direct access to the left ureter and uterine pedicle. This access can be extended to the right side when performing a transverse extrafascial hysterectomy from left to right. The procedure starts from the left extraperitoneal space, where the left uterine artery is sectioned and the vesicovaginal and rectovaginal septa are developed, without opening the peritoneum. Colpotomy is performed from the left to the right side. Once the right ureter is identified, the right uterine artery can be safely transected. Alternatively, the right uterine artery can be sealed and sectioned during the right pelvic lymphadenectomy. At the end of the procedure the peritoneum is opened to complete the surgery.

Measurements And Main Results: Between May 2015 and February 2016, 16 consecutive obese patients were successfully treated using this technique. Median patient age was 62 years (range, 44-78), and median body mass index was 32.5 kg/m (range, 26-42). In 3 cases the right uterine artery was sealed during the right pelvic lymphadenectomy, in 11 cases after completing vaginal opening, and in 2 cases after peritoneal opening. The median operative time was 137.5 minutes (range, 66-260). The median blood loss was 85 mL (range, 0-260), and no blood transfusion was required in any of our 16 patients. No significant complications occurred.

Conclusion: The full extraperitoneal approach represents an interesting alternative strategy for the surgical treatment of obese patients with high-risk endometrial cancer.
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http://dx.doi.org/10.1016/j.jmig.2017.11.019DOI Listing
May 2019

Cancer de l’ovaire : prise en charge pluridisciplinaire du cancer de l’ovaire en première ligne: Recommandations Saint-Paul-de-Vence 2016.

Bull Cancer 2017 May;104 Suppl 1:S6-S15

Département d'oncologie médicale, centre François-Baclesse, Caen, France.

Ovarian Cancer, First Line, Multidisciplinarity: Recommendations for the clinical practice of Nice-Saint-Paul de Vence The treatment of advanced epithelial ovarian cancer is multidisciplinary involving surgical teams and surgery and medical oncology, experienced in the management of this disease, following published quality criteria. The strategy must be validated in multidisciplinary consultation meeting (RCP) before any treatment. The pre-therapeutic assessment includes the histological diagnosis, evaluation of the tumor extension (biological assessment, markers, imaging, laparoscopy), assessment of the general state (operability), in order to answer the question of feasibility of an initial optimal surgery. The standard treatment involves complete surgical resections of the lesions by median laparotomy, followed by adjuvant chemotherapy based on carboplatin and paclitaxel, six cycles with the possibility of treatment with bevacizumab during adjuvant treatment and in maintenance. If complete surgery is not feasible as a result of the initial assessment, interval debulking surgery is considered after 3 to 4 courses of induction chemotherapy.
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http://dx.doi.org/10.1016/S0007-4551(17)30157-1DOI Listing
May 2017
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