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Objectives: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL)., Methods: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models., Results: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS., Conclusions: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials., Competing Interests: Declaration of Competing Interest The authors have nothing to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to analyse the endometrial cancer (EC) patterns of recurrence based on a large French multicentre database according to ESMO-ESGO-ESTRO classification., Methods: Data of women with histologically proven EC who received primary surgical treatment between January 2001 and December 2012 were retrospectively abstracted from seven institutions with prospectively maintained databases. The endpoints were recurrence, recurrence free survival (RFS) and overall survival (OS). Time to the first EC recurrence in a specific site was evaluated by using cumulative incidence analysis (Gray's test)., Results: Data from 829 women were analysed in whom recurrences were observed in 176 (21%) with a median and mean time to recurrence of 13 and 19.5months, respectively. High (35%) and high-intermediate risk groups (16%) were associated with higher recurrence rates compared with low (9%) and intermediate (9%) risk patients (p<0.0001). Women with high risk EC had a higher 5-year cumulative incidence of distant recurrence (20.7%) than women with high-intermediate, intermediate and low risk EC (5.6%, 3.5%, 3.3%), (p<0.001), respectively. Women with high risk and high-intermediate risk EC had a higher 5-year cumulative incidence of loco-regional recurrence (24.3% and 16.6%, respectively) than women with intermediate and low risk EC (6.6% and 6.5%, respectively), (p<0.001)., Conclusions: We report specific time and site patterns of first recurrence according to the ESMO/ESGO/ESTRO classification. Sites and hazard rates for recurrence differ widely between subgroups over time. Defining patterns of EC recurrence may provide useful information for developing follow-up recommendations and designing therapeutic approaches., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: We report the long-term results of the SENTI-ENDO study evaluating the impact of sentinel lymph node (SLN) biopsy on management and survival in patients with early stages of endometrial cancer (EC)., Methods: Patients with FIGO stage I-II EC underwent pelvic SLN biopsy after cervical dual injection (technetium and patent blue) and systematic pelvic node dissection. This study is a secondary endpoint reporting the long-term recurrence free survival (RFS) and the impact of the SLN procedure on adjuvant therapies., Results: The median follow-up was 50 months (range: 3-77 months). Eighteen of the 125 patients (14.4%) experienced a recurrence. The 50-month recurrence-free survival (RFS) was 84.7% with no difference between patients with and without detected SLN (p = 0.09). Among patients with detected SLN (111), no difference in RFS was observed between those with and without positive SLN (p = 0.5). In the whole population, adjuvant therapy was performed in low-, intermediate- and high-risk groups in 31 of 64 patients (48.4%), 28 of 37 patients (75.7%) and 14 of 17 patients (82.3%), respectively (p = 0.0001). For the 111 patients with detected SLN, EBRT was performed in 27 of the 89 with negative SLN and in 11 of the 14 with positive SLN (p = 0.001). Chemotherapy was performed more frequently in patients with positive SLN (6/12, 50%) than in patients with negative SLN (7/56, 12.5%) (p = 0.009)., Conclusions: Our results support the impact of SLN biopsy on surgical management and indications for adjuvant therapies. Further studies are required to assess the clinical impact of the SLN biopsy in early stage EC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: While the accuracy of the Sentinel Lymph Node (SLN) procedure has been validated in patients with early-stage endometrial cancer (EC) at low and intermediate risk of recurrence, its relevance for high-risk EC remains unknown. The aim of this study was to evaluate the contribution of SLN biopsy in staging patients with presumed high-risk EC., Methods: This retrospective multicenter study, conducted from January 2001 to December 2012, included 180 patients with early-stage EC undergoing SLN biopsy. Detection rate and false negative rate were assessed according to risk groups of recurrence., Results: SLNs were detected in 159/180 patients (88%) and were bilateral in 63% of cases. Of the 180 patients, 41 (22%) had a positive lymph node. Ultrastaging detected metastases undiagnosed by conventional histology in 17/41 patients (41%). The false negative rate was 6% (9/159); 2.3% in the low/intermediate risk group and 20% in the high-risk group (p = 0.0008). Lymphovascular space invasion (LVSI) was present in 48 patients (27%). Preoperative findings classified 146 patients as ESMO low/intermediate risk (81%) and 34 as high risk (19%). Ten of the 34 patients (29%) in the presumed high-risk group were downstaged on final histology and 5/18 patients (28%) initially diagnosed with type 2 were finally classified as having type 1 EC. Classification was more likely discordant for patients with preoperative type 2 EC (p = 0.03) and in the initial high-risk group (p = 0.02)., Conclusions: SLN biopsy associated with LVSI status can select which high-risk patients with EC would benefit from comprehensive staging., (Copyright © 2014. Published by Elsevier Inc.)

Objective: DNA repair mechanisms, environment-mediated drug resistance and cancer initiating cells (CIC) are three major research concepts that can explain the chemoresistance of epithelial ovarian cancer (EOC). The objective was to test if changes in the expression of potential markers associated with drug resistance before and after chemotherapy would correlate with platinum resistance, defined as a recurrence within the first year after chemotherapy cessation, and with survival, in advanced EOC., Methods: We included 32 patients with stage IIIC-IV EOC who underwent laparoscopy to evaluate the extent of carcinomatosis, neoadjuvant chemotherapy (carboplatin/taxol) and interval surgery. Biopsies taken during the initial laparoscopies and interval surgeries were evaluated using immunohistochemistry for the expression of 7 proteins: CD117, CD44 and ALDH1 to evaluate CIC; IL-6, IL-8 and BMP2 to evaluate environment-mediated drug resistance; and ERCC1 to evaluate DNA repair. Expression measurements were correlated with platin resistance and survival. The markers' relevance was confirmed in vitro using chemoresistance tests and flow cytometric measurements of the proportion of CD44+ cells., Results: 17 patients were chemoresistant and 15 patients were chemosensitive. We observed increases in CD44, IL-6 and ERCC1 expression and stable ALDH1, CD117, IL-8, and BMP2 expression. Reduced expression of cancer initiating cell markers and increased expression of environment-mediated drug resistance markers were associated with poor prognosis. We also demonstrated that CD44+ cells had survival advantages in vitro., Conclusions: Changes in CD44 and IL-8 expression on tumor cells appeared to correlate with overall survival and should be further tested as predictors of chemoresistance using larger cohort., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To evaluate the different kinetic parameters of serum CA125 during neoadjuvant chemotherapy (NAC) to predict optimal interval debulking surgery (IDS)., Methods: The present retrospective multicenter study included patients with advanced ovarian cancer treated with neoadjuvant platinum-based chemotherapy followed by IDS between 2002 and 2009. Demographic data, CA125 levels, radiographic data, chemotherapy and surgical-pathologic information were obtained. Univariate and multivariate analyses were performed to evaluate variables associated with complete IDS. ROC analysis was used to determine potential cut-off values to predict the likelihood of complete cytoreduction via IDS., Results: One hundred and forty-eight patients met the study criteria. Ninety-three patients (62.8%) had optimal cytoreduction with no residual macroscopic disease (CC-0) after IDS. In multivariate analyses, the CA125 level after the 3rd NAC was an independent predictor for optimal cytoreduction (odds ratio: 0.98 [0.97-0.99], p=0.04). The area under the ROC curve was 0.73. A threshold of 75 UI/ml displayed the most predictive power. The odds ratio to predict complete cytoreduction was 3.29 [1.56-7.10] (p=0.0008)., Conclusion: Our data indicate that for advanced ovarian cancer, a CA125 level less than 75 UI/ml after the 3rd NAC was an independent predictor factor for complete IDS., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The aim of this study is to assess the impact of sentinel lymph node (SLN) mapping and ultrastaging on the therapeutic management of early-stage endometrial cancer., Methods: This retrospective multicenter study covered the period from January 2000 through December 2012 and included 304 women with presumed low- or intermediate-risk endometrial cancer. Node staging, histology results, and the effects of both on therapeutic management were assessed in two groups: those who underwent the SLN mapping and ultrastaging procedure and those treated in accordance with French guidelines., Results: The SLN procedure detected metastatic lymph nodes in three times more women than lymphadenectomy did (16.2% versus 5.1%, p=0.03). Specifically, it found 7 macrometastases (5.1%) and 15 micrometastases (11%); 11 of the latter (8.1%) were detected by serial sectioning and immunohistochemistry (IHC), that is, pathologic ultrastaging. The SLN biopsy false-negative rate was 0% (95% CI: 0-1.6%). This ultrastaging enabled us to modify the adjuvant therapy for half the patients. Women with micrometastases detected by the SLN procedure were treated with external beam radiotherapy (EBRT), while those whose SLN biopsies were negative received vaginal brachytherapy (VBT) or clinical follow-up. SLN biopsies had no impact on recurrence-free survival., Conclusion: SLN mapping and ultrastaging improved staging and made it possible to adapt adjuvant therapy to risk of recurrence., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Differentiation between grade-1 endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) is crucial to determine optimal surgical management. However, discrepancies exist between preoperative diagnosis of AEH and final histology. Our aim was to establish clusters of immunohistochemical markers to distinguish AEH from grade-1 EC., Methods: We studied 13 immunohistochemical markers (steroid receptors, pro/anti apoptotic proteins, metalloproteinases (MMP) and tissue inhibitor of metalloproteinase (TIMP), and CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating grade-1 EC from AEH., Results: From 42 tissue samples (20 ECs and 22 AEHs), we found 3 clusters of co-expressed proteins: Cluster 1 included 3 proteins (over-expression of MMP-9 and under-expression of estrogen receptor (ER) and progesterone receptor (PR) A in grade-1 EC compared to AEH); cluster 2 showed an MMP-9 over-expression and ER under-expression; cluster 3 showed over-expression of MMP-9 and bcl-2 and under-expression of ER, PR A and CD44-v6 variant. These three clusters together predicted grade-1 EC with a misclassification rate of 8%., Conclusion: Supervised clustering of immunohistochemical markers in grade-1 EC and AEH tissue identified proteins acting together and resulted in accurate differentiation between these two histological entities., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to build a model to predict the risk of lymph node metastases (LNM) in women with low- or intermediate-risk endometrial cancer (EC) using histological and immunohistochemical markers., Methods: Samples were collected from 68 women with low- or intermediate-risk EC. European Society of Medical Oncology (ESMO) risk group, lymphovascular space involvement (LVSI), immunostaining expressions of Estrogen receptor (ER) and Progesteron receptor (PR) were used to build a recursive partitioning model to predict final lymph node status., Results: The number of women with final low- and intermediate risk EC was 34 (50%) each. LVSI was present in 7 women with low-risk (20%) and 28 (80%) with intermediate-risk EC. Nineteen women (28%) had LNM at final histology. A lower immunostaining of ER (p=0.02) and PR (p=0.03) was found in women with LNM compared with those without. Women were correctly classified by the model in 87% of cases; among the 56 women without LNM that were predicted, 48 (86%) had no LNM at final histology. Among the 12 women with LNM predicted, 11 (92%) had LNM at final histology., Conclusions: Our results show that lymph node status can be predicted with a relatively high accuracy in women with low- or intermediate-risk EC. This can help physicians to better adapt surgical staging and adjuvant therapies., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: Sentinel lymph node (SLN) biopsy is a surgical procedure proposed in early cervical cancer. This technique yields the potential interest to reduce the morbidity of complete lymphadenectomy, which could then be performed only in case of positive SLN. Intraoperative examination has a major per-operative role in predicting nodal involvement and preventing a second step procedure. The aim of this study was to assess the diagnostic value of intraoperative examination with frozen section (FS) or imprint cytology (IC) of SLNs in early cervical cancer., Methods: Prospective study in 7 centers (01/2005-06/2007) including patients with stage IA1 and lymphovascular space involvement to IB1 cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma). SLNs were detected with a combined method (Tc99m+blue dye) and then removed laparoscopically. Intraoperative examination (FS or IC) was not systematically performed but recommended in case of macroscopical nodal enlargement in 5 centers. Results of intraoperative examination were compared with final histology performed by Hematoxylin-Eosin-Safran staining and immunohistochemistry. The diagnostic value of intraoperative examination was calculated., Results: One hundred and thirty-nine patients were analyzed in the study. The combined detection rate was 97.8% per patient, with 454 detected SLNs. One hundred and two patients (73.4%) had an intraoperative examination (97 patients with FS and 5 with IC). Among patients with intraoperative examination, 5 SLNs were positive (all with macrometastasis at final histology), as compared with 22 metastatic nodes at final result. The 17 false negative SLNs were: 4 macrometastasis, 4 micrometastasis and 9 isolated tumor cells. Sensitivity of the intraoperative examination per node was 20.7% [95%CI: 7.8%-45.4%] and the negative predictive value 93.0% [95%CI: 89.0%-95.9%]., Conclusions: Intraoperative examination of SLNs by FS and IC has a poor diagnostic value. This is mainly related to micrometastasis and isolated tumor cells, which are not detected by intraoperative techniques. Other techniques, like new molecular assays, should be investigated to improve intraoperative assessment of SLNs., (Copyright © 2011. Published by Elsevier Inc.)

Objective: Lymph node status in endometrial cancer is a major prognostic factor. Sentinel lymph node (SLN) biopsy using radiocolloid and blue dye labeling has emerged as an alternative to systematic lymphadenectomy. This technique requires a preoperative lymphoscintigraphy. The aim of this study was to evaluate the limits of day-before preoperative lymphoscintigraphy to SLN biopsy., Methods: Between July 2002 and March 2007, 38 patients with endometrial cancer underwent laparoscopic SLN procedure using radiocolloid and blue dye. Those with early-stage I endometrial cancer (35 patients) underwent a SLN procedure followed by systematic pelvic lymphadenectomy and a hysterectomy with bilateral salpingo-oophorectomy while those with presumed stage IIB on MR imaging (3 patients) underwent a radical hysterectomy. Omentectomy and paraaortic lymphadenectomy were also performed for women with clear cell or serous papillary carcinoma (5 patients). The SLN identification rates and false-negative rates were studied., Results: The detection rate of lymphoscintigraphy was 84.5% (32/38), with 1.9 nodes per patient. Eight of 17 patients (47%) with unilateral sentinel lymph node on lymphoscintigraphy had bilateral SLNs at surgery and three of 15 patients (20%) with bilateral SLN on lymphoscintigraphy had unilateral SLN at surgery. The correlation was poor (kappa=0.266). When categorized in <2 and > or =2 sentinel nodes, the correlation between lymphoscintigraphic and surgical SLN mapping was moderate (kappa=0.33)., Conclusion: Our results demonstrated the low correlation between day-before lymphoscintigraphy and surgical SLN mapping raising issues of its usefulness and cost-effectiveness in routine practice.

Background: The relevance of laparoscopy-based score in identifying patients with advanced ovarian cancer for optimal cytoreductive surgery has been evaluated., Methods: 55 patients with stage III-IV ovarian cancer, having undergone both laparoscopy and laparotomy for cytoreductive surgery, were retrospectively analyzed. Seven parameters were assessed: omental cake, peritoneal carcinosis, diaphragmatic carcinosis, mesenteric retraction, bowel infiltration, stomach infiltration, liver metastases. Each parameter was assigned 2 points if present and 0 if not (Fagotti score). Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy were calculated for each parameter. Receiver Operating Characteristic (ROC) curve analysis was used to predict the surgical outcome., Results: A laparoscopy-based score of >or=8 was associated with suboptimal cytoreduction with sensitivity, specificity, PPV, NPV, and accuracy of 46%, 89%, 89%, 44%, and 60% respectively. ROC curve analysis gave an Area Under the Curve (AUC) of 0.74. A modified score was set up by selecting 4 of the 7 parameters which satisfied the inclusion criteria in our population: diaphragmatic carcinosis, mesenteric retraction, stomach infiltration, liver metastases. Thirteen patients (12%) had a modified score of >or=4 and 42 patients (88%) had a score of <4 with an optimal cytoreduction rate of 0% and 43% respectively (P=0.002). A modified score of >or=4 was associated with suboptimal cytoreduction with sensitivity, specificity, PPV, NPV, and accuracy of 35%, 100%, 100%, 43%, and 56% respectively. ROC curve analysis gave an AUC of 0.68., Conclusion: This simplified laparoscopy-based score was at least as accurate as the Fagotti score to predict resectability.

Objective: The required radicality of hysterectomy for women with early-stage cervical cancer is controversial owing to the risk of severe complications. The aim of this study was to determine the contribution of the sentinel node (SN) procedure to tailoring the radicality of hysterectomy in women with cervical cancer., Methods: Between April 2001 and December 2005, 54 patients with early-stage or locally advanced cervical cancer underwent laparoscopic sentinel node (SN) biopsy based on combined patent blue and radiocolloid detection. Thirty-nine patients with early-stage cervical cancer underwent a laparoscopic SN procedure with complete pelvic lymphadenectomy and radical hysterectomy. Moreover, 15 women with locally advanced cervical cancer underwent an SN procedure with pelvic and para-aortic lymphadenectomy before concurrent neoadjuvant chemoradiotherapy., Results: The SN detection rate was 83.3%. The detection rate was higher in women with early-stage disease (90%) than in women with more advanced disease (66.6%) (p=0.03). At final histology, 14 metastatic SN were found in 11 (21.3%) of the 54 patients. They comprised macrometastases in 6 SN, micrometastases in 5 SN, and isolated tumour cells in 3 SN. Parametrial involvement with negative sentinel nodes was found in 15.1% of cases. The overall sensitivity, specificity, positive and negative predictive values and accuracy of intraoperative imprint cytology were 20%, 100%, 100%, 79.5% and 80.5%, respectively. Among the 39 women with early cervical cancer, five (12.8%) had parametrial involvement. In univariate analysis, parametrial involvement was significantly associated with large tumour size, advanced-stage disease, positive pelvic lymph nodes and lymphovascular space involvement. Parametrial involvement tended to be associated with positive sentinel nodes., Conclusion: These results underline the contribution of the SN procedure to evaluating lymph node status. However, intraoperative imprint cytology appeared poorly accurate, and further histological or biological tools are needed to evaluate SN status and, hence, to tailor the radicality of hysterectomy.

Background: The risk of wound metastasis after laparoscopic management of early-stage cervical cancer is well known, but there are few data on peritoneal carcinomatosis of cervical adenocarcinoma., Case: We report the first case of peritoneal carcinomatosis occurring in a woman with FIGO stage Ib1 cervical adenocarcinoma who underwent laparoscopic type III radical hysterectomy and bilateral pelvic lymphadenectomy (sentinel node procedure) followed by vaginal brachytherapy. A peritoneal recurrence was diagnosed 16 months after surgery and was treated with chemotherapy and laparotomy., Conclusion: Laparoscopy for cervical adenocarcinoma may carry a risk of peritoneal dissemination.

Background: Positron emission tomography and computed tomography (PET/CT) have a potential role in detecting and locating recurrent ovarian cancer. Precise tumor location during surgical treatment is often difficult, owing to limited tumor size and post-surgical anatomic modifications. The surgical gamma probe, which has become increasing popular in recent years with the development of sentinel node mapping, may improve tumor detection and facilitate resection of occult metastases., Case Report: We describe the first case of laparoscopic resection of occult metastasis using the combination of FDG-PET/CT image fusion with intraoperative FDG-sensitive probing in a patient with recurrent ovarian cancer., Conclusion: FDG-sensitive probe combined with preoperative PET/CT image fusion can help to detect occult metastasis and guide laparoscopic excision.

Background: Laparoscopic pelvic lymph node dissection in combination with a vaginal radical Schauta-Amreich operation has become an alternative for women with early-stage cervical cancer., Case: We described the first case of metastasis on Schuchardt's incision after Schauta-Amreich operation for neuroendocrine cervical cancer., Conclusion: Metastasis on Schuchardt's incision after Schauta-Amreich operation can rarely be the metastatic localization of the cervical carcinoma.

Aims: We aimed to compare the expression patterns of E-cadherin and CD44 isoforms in cervical intraepithelial neoplasia (CIN) between patients with or without infection by the human immunodeficiency virus (HIV)., Methods: An immunohistochemical analysis using the monoclonal antibody HECD-1 against E-cadherin and the monoclonal antibodies 2C5, binding to CD44s and all the variants encoded by exons 3 to 10, 3G5, specific for CD44v3 and 2F10, and specific for CD44v6, was performed in formalin-fixed, paraffin-embedded samples of 138 CIN (74 from HIV-negative and 64 from HIV-positive patients)., Results: In HIV-negative patients, the mean percentages (+/-SD) of E-cadherin-positive cells in CIN of grades I, II, and III were, respectively, 33% +/- 4, 63% +/- 5, and 91% +/- 9. The difference was statistically significant between the three groups of tumors (P < 0.0001). In HIV-negative patients, the mean percentages (+/-SD) of CD44-positive cells in CIN of grades I, II, and III were, respectively, 37% +/- 7, 57% +/- 8, and 90% +/- 11. The difference was statistically significant between the three groups of tumors (P < 0.0001). No difference in E-cadherin and CD44 expressions was noted between HIV+ and HIV- women. Further analysis showed no relation between E-cadherin or CD44 expression and the HPV status and CD4 T cell serum levels., Conclusion: Our study confirms that alterations in E-cadherin and CD44 expression in CIN depend on the histological grade but suggest nondirect involvement and are not related to HIV and immune status., (Copyright 2000 Academic Press.)