Emilie Raimond

Impact of sentinel lymph node biopsy on the therapeutic management of early-stage endometrial cancer: Results of a retrospective multicenter study

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.

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

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

External validation of nomograms designed to predict lymphatic dissemination in patients with early-stage endometrioid endometrial cancer: a multicenter study

OBJECTIVE The objective of the study was to externally validate and assess the robustness of 2 nomograms designed to predict the probability of lymphatic dissemination (LD) for patients with early-stage endometrioid endometrial cancer. STUDY DESIGN Using a prospective multicenter database, we assessed the discrimination, calibration, and clinical utility of 2 nomograms in patients with surgically treated early-stage endometrioid endometrial cancer. RESULTS Among the 322 eligible patients identified, the overall LD rate was 9.9% (32 of 322). Predictive accuracy according to discrimination was 0.65 (95% confidence interval, 0.61-0.69) for the full nomogram and 0.71 (95% confidence interval, 0.68-0.74) for the alternative nomogram. The correspondence between observed recurrence rate and the nomogram predictions suggests a moderate calibration of the nomograms in the validation cohort. CONCLUSION The nomograms were externally validated and shown to be partly generalizable to a new and independent patient population. Although these tools provide a more individualized estimation of LD, additional parameters are needed to allow higher accuracy for counseling patients in clinical practice.

Patterns of recurrence and outcomes in surgically treated women with endometrial cancer according to ESMO-ESGO-ESTRO Consensus Conference risk groups: Results from the FRANCOGYN study Group

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 (Grays 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.

Predicting poor prognosis recurrence in women with endometrial cancer: A nomogram developed by the FRANCOGYN study group

Background:The purpose of this study was to develop a nomogram to predict ‘poor prognosis recurrence’ (PPR) in women treated for endometrial cancer (EC).Methods:The data of 861 women who received primary surgical treatment between January 2001 and December 2013 were abstracted from a prospective multicenter database. Data were randomly split into two sets: training and validation with a predefined 2/3 ratio. A Cox proportional hazards multivariate model of selected prognostic features was performed in the training cohort (n=574) to develop a nomogram predicting PPRs. The nomogram was validated in the validation cohort of 287 patients.Results:In the training cohort, 82 (14.3%) developed subsequent PPR. Age, histologic type and grade, lymphovascular space invasion status, FIGO stage, and nodal staging (SLN±pelvic and/or para-aortic lymphadenectomy) were independently associated with subsequent PPR. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.82 (95% confidence interval (CI), 0.73–0.89) in the training set. The validation set showed a good discrimination with an AUC of 0.75 (95% CI, 0.65–0.83).Conclusions:We have developed a robust tool that is able to predict subsequent PPRs in women with FIGO I–III EC.

An external validation study of nomograms designed to predict isolated loco-regional and distant endometrial cancer recurrences: how applicable are they?

Background:To externally validate and assess the robustness of two nomograms to predict the recurrence risk of women with endometrial cancer (EC).Methods:Using an independent, multicentre external patient cohort we assessed the discrimination and calibration of two nomograms – the 3-year isolated loco-regional (ILRR) and distant (DR) recurrence nomograms – in women with surgically treated stage I–III EC.Results:Two hundred and seventy one eligible women were identified from two university hospital databases and the Senti-Endo trial. The median follow-up and initial recurrence time were 38.1 (range: 12–69) and 22.0 (range: 8.3–55) months, respectively. The overall recurrence rate was 13.8% (37 out of 271). Predictive accuracy according to the discrimination was 0.69 (95% CI, 0.58–0.79) and 0.66 (95% CI, 0.60–0.71) for the 3-year ILRR and DR nomograms, respectively. The correspondence between observed recurrence rate and the nomogram predictions suggests a moderate calibration of the nomograms in the validation cohort.Conclusion:The nomograms were externally validated and shown to be partly generalisable to a new and independent patient population. The tools need to be improved by including information on the lymph node status and adjuvant therapies.

Morphometric Analysis of the Umbilicus According to Age

Background Morphometric and anatomical analyses of the shape and position of the umbilicus have been conducted in adults, but umbilicoplasty in children remains challenging because growth is still occurring. Objectives The main objective of this study was to evaluate the difference in the position and shape of the umbilicus between childhood and adulthood. The secondary objective was to improve the surgical management of umbilicoplasty in children. Methods This prospective single-center study focused on the morphometric analysis of the umbilicus in 200 adults and children. All data, including standardized measures and pictures, were determined by one single operator. Results Despite a variation of approximately 2% in the xiphoid-pubis distance, the location of the umbilicus remains stable during the entire growth period. In a supine individual, the location is at one half to two thirds of the xiphoid-pubis distance (slightly lower in children), with a mean ratio of 0.57 for the xiphoid-umbilicus distance to the xiphoid-pubis distance. In the general population, the most common shapes are round and vertical oval. T-shaped umbilici were only observed in adults. Round and protruding shapes were twice as frequent in children under 18 as in adults. The horizontal oval shape was twice as frequent in adults. Conclusions Abdominal growth and changes in the repartition of subcutaneous adipose tissues with age are responsible for the vertical orientation and deepening of the umbilicus as well as its horizontal orientation. To promote final cosmetic outcomes, secondary umbilicoplasty must place the umbilicus between one half and two thirds of the xiphoid-pubis distance. Level of Evidence 4

Delayed postpartum hemorrhage by traumatic lesion of uterine vessel without pseudo-aneurysm.

contrast, there are positive outcomes for endoscopic mesh removal in a recent report [4]. With the electrode loop, the mesh can be resected down to the submucosal layer, even in the bladder neck or urethra. Our patient also showed a success outcome after the transurethral resection procedure. The duration from the manifestation of symptoms to diagnosis may take more than 4 years [5]. The possibility of unrecognized bladder injury and cystosopic examination should be considered in women with lower urinary tract symptoms after a midurethral sling or TVM procedure. Our results suggested that transurethral resection appears to have a good outcome for the treatment of Delayed postpartum hemorrhage by traumatic lesion of uterine vessel without pseudo-aneurysm